title: Sex hormone binding globulin, cortisol binding globulin, thyroxine binding globulin, ceruloplasmin: changes in treatment with two oral contraceptives low in oestrogen. Oral contraceptive tablets containing 20 and 30 micrograms of ethinyl estradiol with 150 micrograms desogestrel. Their influence on lipids, lipoproteins, sex hormone binding globulin and testosterone. Clinical comparison of triphasic norgestimate/35 micrograms ethinyl estradiol and monophasic norethindrone acetate/20 micrograms ethinyl estradiol. Cycle control, lipid effects, and user satisfaction. A double blind randomized control trial, comparing effect of drospirenone and gestodene to sexual desire and libido. Oral contraceptives, androgens, and the sexuality of young women: II. The role of androgens Does oral contraceptive-induced reduction in free testosterone adversely affect the sexuality or mood of women? Desogestrel+ethinylestradiol versus levonorgestrel+ethinylestradiol. Which one has better affect on acne, hirsutism, and weight change. Testosterone and sexual behavior in oral contraceptive users and nonusers: A prospective study The effect of monophasic combinations of ethinyl estradiol and norethindrone on gonadotropins, androgens and sex hormone binding globulin: a randomized trial. Effect of low-dose oral contraceptives on androgenic markers and acne. Relation of androgen receptor sensitivity and mood to sexual desire in hormonal contraception users. [Ovarian suppression with Diane 35/50]. Comparison of the skeletal effects of the progestogens desogestrel and levonorgestrel in oral contraceptive preparations in young women: controlled, open, partly randomized investigation over 13 cycles. A cross-over study of three oral contraceptives containing ethinyloestradiol and either desogestrel or levonorgestrel. Preliminary study on the effect of four-phasic estradiol valerate and dienogest (E2V/DNG) oral contraceptive on the quality of sexual life. Measurement of free testosterone in normal women and women with androgen deficiency: comparison of methods. Pharmacokinetics of levonorgestrel and ethinylestradiol in 14 women during three months of treatment with a tri-step combination oral contraceptive: serum protein binding of levonorgestrel and influence of treatment on free and total testosterone levels in the serum. Comparative evaluation of the androgenicity of four low-dose, fixed-combination oral contraceptives. Changes in androgens during treatment with four low-dose contraceptives. Associations among oral estrogen use, free testosterone concentration, and lean body mass among postmenopausal women. Age-specific reference ranges for serum testosterone and androstenedione concentrations in women measured by liquid chromatography-tandem mass spectrometry. Effects of two combined hormonal contraceptives with the same composition and different doses on female sexual function and plasma androgen levels. Effect of oral versus transdermal steroidal contraceptives on androgenic markers. Total testosterone assays in women with polycystic ovary syndrome: precision and correlation with hirsutism. Effects of oral contraceptive combinations containing levonorgestrel or desogestrel on serum proteins and androgen binding. Effect of four different oral contraceptives on various sex hormones and serum-binding globulins. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function Validity of free testosterone and free estradiol determinations in serum samples from postmenopausal women by theoretical calculations. The effect of different contraceptive treatments on the serum concentration of dehydroepiandrosterone sulfate. [Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations]. Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women. ANDROGENS AND SEXUAL BEHAVIOUR IN WOMEN USING ORAL CONTRACEPTIVES Clinical and hormonal effects of two contraceptives: correlation to serum concentrations of levonorgestrel and gestodene. A single-dose and 3-month clinical—pharmacokinetic study with a new combination oral contraceptive Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone. Reproductive hormones and skeletal health in young women. A randomized cross-over study on various hormonal parameters of two triphasic oral contraceptives. Inhibition of ovulation by an oral contraceptive containing 100 micrograms levonorgestrel in combination with 20 micrograms ethinylestradiol. Effect of two oral contraceptives containing ethinylestradiol and gestodene or norgestimate upon androgen parameters and serum binding proteins. Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use. Minimal androgenic activity of a new oral contraceptive containing norethindrone acetate and graduated doses of ethinyl estradiol. Effects on blood lipid and androgen levels of two triphasic oral contraceptives. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol on ovarian function in comparison to a monophasic combined oral contraceptive containing drospirenone and ethinylestradiol Diurnal rhythm and effects of oral contraceptives on serum dehydroepiandrosterone sulfate (DHEAS) are related to alterations in serum albumin rather than to changes in adrenocortical steroid secretion Effects of continuous versus cyclical oral contraception: a randomized controlled trial.
abstract: It is generally assumed that the oral contraceptives cause the carrier proteins to change . Notoriously this effect is used to evaluate indirectly their estrogenicity/gestagenicity ratio . In order to assess the residual intrinsic and rogenic activity of two new 19-nor-derivative components , Desogestrel ( DG ) 150 micrograms and Gestodene ( GD ) 75 micrograms , both in association with Ethinylestradiol ( EE ) 30 micrograms , Sex Hormone Binding Globulin , Thyroxine Binding Globulin , Ceruloplasmin and Free And rogen Index ( FAI ) , were studied in 40 young normally cycling healthy volunteers , matched for body mass index and age . The participants were r and omly assigned to either EE-DG or EE-GD treatment . A marked significant increase in all the carrier proteins was found . Conversely , the values for FAI decreased significantly . The changes in the two groups were substantially of the same magnitude . These results are an indirect confirmation of the well-known negligible receptor binding affinity of the two progestogen in vitro , also supporting for these compounds the lack of relevant and rogenic effects The effect of two oral contraceptive ( OC ) pills , both containing 150 micrograms of desogestrel , but with 20 ( Mercilon ) or 30 micrograms ( Marvelon/Desolett ) of ethinyl estradiol on plasma levels of lipids , lipoproteins and sex hormone binding globulin ( SHBG ) , total and free testosterone were compared in a double-blind , r and omized , two-center study in a total of 60 women over one year . A significant rise with Marvelon but not with Mercilon was seen in total cholesterol , HDL cholesterol , HDL-3 and apolipoprotein B , whereas LDL cholesterol decreased with Mercilon only . These effects result ed in significant differences between the two groups in the magnitude of responses in all these parameters except HDL-3 . HDL-2 , apolipoprotein A-1 and total phospholipids were elevated with both pills after treatment and with no difference in the degree of response between groups . The HDL/LDL cholesterol ratio tended to increase in both groups and that of apolipoproteins A-1/B in the women on Mercilon . Total triglycerides increased in both groups , but more in the women on Marvelon . Total testosterone decreased , particularly in the Marvelon group , whereas the two pills caused a similar increase in SHBG and decrease in free testosterone . It is concluded that the direction of changes in plasma lipids and lipoproteins with both these pills may as a whole be interpreted as beneficial , and that the differences in effect on LDL cholesterol and apolipoprotein B may suggest a slightly advantageous effect of Mercilon in this aspect . However , the clinical significance of these changes is uncertain . The results indicate a lack of and rogenicity of both pills This six-cycle , multicenter , open-label , r and omized study compared the clinical experience of two low-dose oral contraceptives ( OC ) : a triphasic OC containing norgestimate ( NGM ) and 35 micrograms ethinyl estradiol ( EE ) ( Ortho Tri-Cyclen ) and a monophasic OC containing norethindrone acetate ( NETA ) and 20 micrograms EE ( Loestrin Fe 1/20 ) .  Cycle control , lipid and and rogen profiles , and user satisfaction were studied in new-start OC users ( i.e. , no prior use within 60 days ) .  Breakthrough bleeding or breakthrough spotting ( BTB/BTS ) occurred in a significantly smaller percentage of NGM/EE users than NETA/EE users during each of six cycles ( p < or = 0.002 ) . The incidence of BTB/BTS ranged from 3.7 % to 13.5 % for NGM/EE users and from 23.5 % to 49.7 % for NETA/EE users . Significantly fewer NGM/EE users than NETA/EE users experienced absence of menses at cycles 2 through 6 ( p < or = 0.003 ) . The percentages of women having no menses at each cycle ranged from 0.9 % to 4.7 % for NGM/EE users and from 10.3 % to 21.3 % for NETA/EE users . NGM/EE users reported a significantly ( p < 0.001 ) higher level of satisfaction with their OC at the end of six cycles than did NETA/EE users , but there was no significant difference in compliance , discontinuation rates , or adverse events between the two groups . NGM/EE produced a significantly ( p < or = 0.001 ) greater beneficial effect on HDL-C , HDL2 , and apo A-I than did NETA/EE . No statistically significant treatment differences were found for total cholesterol , LDL-C , triglycerides , or apo-B. Both OC increased sex hormone binding globulin and decreased free testosterone , but NGM/EE had a significantly greater effect ( p < 0.009 ) BACKGROUND Oral contraceptive is the most commonly used method of fertility control . Yasmin is a combination of a novel progestogen with anti- and rogenic and anti-mineralcorticoid activities ( 3 mg Drospirenone ( DRSP ) and 30 microg ethinylestradiol ( EE ) ) . It has been shown in many clinical trials that Yasmin is an efficacious oral contraceptive , lacking undesired effects as with other oral contraceptives such as weight gain . However the effects of Yasmin on sexual desire and libido have not been intensively investigated so far OBJECTIVE Investigate the effects of Yasmin on sexual desire , libido and changes in the free and rogen index ( FAI ) compare to  Meliane  ( 75 microg gestodene + 20 microg ethinylestradiol ) . MATERIAL AND METHOD The authors ' report the results of a double blind r and omized controlled study using a translated version of the Female Sexual Function Index question naire ( FSFI ) for the assessment of the sexual function . The free and rogen index was calculated from measurements of testosterone and sexual hormone binding globulin . RESULT The result shows statistically significant improvements regarding sexual desire , arousal and overall satisfaction in the Yasmin group . Additionally , an increased frequency of orgasms in the Meliane group was reported . Statistically significant differences between the two treatments regarding changes in the FSFI score and changes in the free and rogen index have not been observed . CONCLUSION The novel oral contraceptive containing drospirenone ( Yasmin ) and the non-anti- and rogenic progestin containing oral contraceptive ( Meliane ) do not show unfavorable effects on sexual response and libido The relationships between plasma free testosterone ( FT ) and measures of sexual attitude , sexual behavior , and gender role behavior were assessed in 55 oral contraceptive-using and 53 nonusing female undergraduates .  Plasma FT and other measures of and rogenicity were substantially lower in the oral contraceptive ( OC ) group . Correlations between FT and certain behavioral and attitudinal measures were found in the OC users but not the nonusers . In the OC users , FT was positively associated with frequency of sexual intercourse but not with frequency of masturbation . It was negatively associated with restrictive sexual morality . Correlations between FT and measures of gender role behavior were negligible , and FT was unrelated to proceptivity , homosexual interest , or the use of sexual fantasy . The occurrence of some predicted correlations among pill-using women but not the nonusers requires explanation , particularly in view of the substantially lower levels of FT in the pill-using group . It is suggested that and rogen — behavior relationships in women are easily obscured by psychosocial influences and in this sample of young women such influences may have been more powerful among those not using OCs . Such psychosocial influences are likely to differ at different stages of women 's life cycles . The importance of controlling for such influences in any study of hormone — sexual behavior relationships in women is emphasized , and the need for prospect i ve studies of women before and after starting on steroidal contraception is recognized The aim of this study was to examine whether changes in plasma and rogen levels ( total testosterone ( T ) , free testosterone ( FT ) , and dehydro-epi and rosterone-sulfate ( DHEA-S ) ) induced by oral contraceptive ( OC ) use were related to changes in sexual interest or response or in mood . Sixty-one women provided blood sample s and were assessed , using interviews and st and ardized question naires , prior to starting , and after 3 months on OCs ( Ortho-Tricyclen , Ortho-Tricyclen-Lo , or Ortho-Cyclen , all containing the same progestagen , norgestimate ) . Significant decreases in T , FT , and DHEA-S were found after 3 months , although the extent of reduction was variable across women . There was some support for a relationship between the degree of reduction in total T and FT and the frequency of sexual thoughts after 3 months on OCs . However , some women had no loss of sexual interest in spite of substantial reduction in FT , and there was overall no evidence that reduction in FT affected enjoyment of sexual activity with a partner . The findings are consistent with the idea that some women may be more sensitive to changes in T than others . No relationship was found between negative mood , as assessed by the Beck Depression Inventory , and changes in T , FT , or OBJECTIVE To compare complications of third and second generation oral contraceptive pills ( OCPs ) . METHODS In a r and omized clinical trial from October 2007 to October 2008 , 100 healthy women of reproductive age referred to Amir Hospital Family Planning Clinic and some heath centers in Semnan , Iran were r and omized in 2 equal groups . They received either a third generation OCP ( 150 microgram desogestrel [ DSG ] + 30 microgram ethinylestradiol [ EE ] ) or a second generation type ( 150 microgram levonorgestrel [ LNG ] + 30 microgram EE ) . Six months later , changes of weight , acne , and hirsutism severity , as well as serum titers of sex hormone-binding globulin ( SHBG ) and free testosterone were compared between the 2 groups . RESULTS Forty-five women were evaluated in the DSG+EE OCP group , and 46 women in the LNG+EE OCP group . The BMI was significantly higher in the second group ( p=0.000 ) after 6 months duration . Likewise , the decrement of acne and hirsutism severity was significantly higher in the DSG+EE users ( p=0.000 ) . Mean changes of serum free testosterone ( p=0.967 ) and SHBG ( p=0.916 ) were comparable between the 2 groups . CONCLUSION In comparison with the LNG+EE OCP , the DSG+EE OCP is a contraceptive pill that significantly decreases the severity of acne and hirsutism , without any significant change in weight The relationship between plasma testosterone ( T ) secretion and patterns of sexual behavior was examined in 18 women using oral contraceptives ( OCs ) and 13 nonusers matched for partner availability . Retrospective assessment s of perimenstrual symptoms , sexual attitudes , and sexual experience were obtained and women completed daily ratings of the frequency of sexual activities and the level of well-being for 1 month . Plasma levels of sex hormone binding globulin ( SHBG ) , progesterone , Total T , Free T , and non-SHBG bound T were determined by radioimmunoassay at four phases of the pill or menstrual cycle . Overall , women not using OCs had higher plasma levels of Total , Free , and non-SHBG bound T and lower plasma levels of SHBG than those of OC users . Further , only nonusers had perimenstrual decreases in plasma levels of Total and Free T. The two groups were comparable on most retrospective measures . However , OC users reported more satisfaction with their sexual partners than did nonusers and prospect i ve monitoring revealed that they engaged in sexual interactions more frequently than did nonusers across the cycle . In contrast , both groups reported a similar frequency of autosexual activities across the cycle . There were no correlations between average levels of T and levels of sexual desire , sexual interactions , or autosexuality . Moreover , only nonusers reported a decrease in levels of sexual desire during the perimenstrual period that was associated with the changes in Free T over the menstrual cycle The effects of different monophasic combinations of ethinyl estradiol and norethindrone on FSH , LH , sex hormone binding globulin , total testosterone , and rostenedione , and dehydroepi and rosterone sulfate levels in non-obese , non-hirsute women were compared . Retrospective analysis of frozen serum from a prospect i ve r and omized trial in which women received one of three oral contraceptive pills containing ethinyl estradiol 50 micrograms/norethindrone 1 mg , ethinyl estradiol 35 micrograms/norethindrone 1 mg or ethinyl estradiol 35 g/norethindrone 0.5 mg for nine cycles was conducted . Blood sample s were obtained prior to treatment and during the third , sixth and ninth pill cycles . Ethinyl estradiol 50 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 1 mg suppressed FSH , LH , and total testosterone and increased sex hormone binding globulin to a similar degree . Ethinyl estradiol 35 micrograms/norethindrone 0.5 mg result ed in less suppression of FSH , LH , and total testosterone , but greater elevation of sex hormone binding globulin . Dehydroepi and rosterone sulfate was suppressed to a similar degree with ethinyl estradiol 35 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 0.5 mg , but ethinyl estradiol 50 micrograms/norethindrone 1 mg result ed in the least suppression of dehydroepi and rosterone sulfate .  Ethinyl estradiol 35 micrograms/norethindrone 1 mg caused greater suppression of and rostenedione than did the other two oral contraceptives . Oral contraceptive-induced changes in gonadotropins , and rogens , and sex hormone binding globulin can be predicted by considering the relative amounts of estrogen and progestin in the pill . When combined with 1 mg of norethindrone , 50 micrograms of ethinyl estradiol did not result in greater suppression of FSH , LH , or total testosterone or in greater elevation of sex hormone binding globulin than did 35 micrograms of ethinyl estradiol Oral contraceptives ( OC ) suppress excess and rogen production ; however , different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin ( SHBG ) and testosterone that may influence clinical outcomes . This multicenter , open-label , r and omized study compared biochemical and rogen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol ( EE , 20 micrograms ) but different progestins , levonorgestrel ( LNG , 100 micrograms ) , and norethindrone acetate ( NETA , 1000 micrograms ) . Fifty-eight healthy women ( 18 - 28 years old ) received three cycles of treatment with LNG/EE ( n = 30 ) or NETA/EE ( n = 28 ) . The results showed that LNG reduced and rogen levels in three compartments -- adrenal , ovarian , and peripheral . NETA reduced only adrenal and peripheral and rogens . Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG , bioavailable testosterone ( T ) was reduced by the same amount with LNG and NETA . Both treatments improved acne and were well tolerated . Low-dose OC ( EE , 20 micrograms ) are effective in reducing circulating and rogens and acne lesions without causing weight gain . Although LNG and NETA affected secondary markers differently , both OC formulations produced an equivalent decrease in bioavailable BACKGROUND Since very little research in this field is available , this study aims to assess the role of psychosexual , relationship , hormonal and genetic measures in the sexual desire of users of three hormonal contraceptive products [ low-dose combined oral contraceptive ( 20 mcg ethinylestradiol/150 mcg desogestrel ) , progestin-only pill ( 75 mcg desogestrel ) and vaginal ring ( daily dose of 15 mcg ethinylestradiol/120 mcg etonogestrel ) ]  . STUDY DESIGN Fifty-five couples were r and omized over three groups in which the women consecutively used each product during 3 months . Both partners repeatedly filled out question naires on solitary and dyadic sexual desire ( desire to behave sexually by oneself or towards a partner ) .  Total and free testosterone , sex hormone binding globulin and a genetic marker of and rogen receptor sensitivity [ cytosine-adenine-guanine ( CAG ) repeat length ] were assessed on blood sample s of the female partners . RESULTS Sexual desire was higher in women with either short or long CAG repeats ( solitary , p=.004 ; dyadic , p=.008 ) . Desire levels were higher during vaginal ring use ( solitary , p=.018 ; dyadic , p=.007 ) . The woman 's mood was found to impact her dyadic sexual desire ( p<.001 ) ; this scale was also strongly associated with the male partner 's dyadic sexual desire ( p<.001 ) . CONCLUSIONS The current study found evidence for a role of and rogen receptor sensitivity and mood in the sexual desire of hormonal contraceptive users In this study , hormone profiles were studied using Diane 35 and Diane 50 before and after treatment for 4 - 25 months . A comparison of the hormone profiles with Diane 35 or Diane 50 should investigate , if both preparations induce complete ovarian suppression , independent of the given dose of ethinyl oestradiol .  43 patients were treated with Diane 35 and 15 women with Diane 50  over a different lengths of time -- up to a period of 25 cycles . Parallel to the determination of the hormone profiles ( luteinising hormone [ LH ] , follicle stimulating hormone [ FSH ] , prolactin , oestrone [ E1 ] , oestradiol [ E2 ] , progesterone , total testosterone [ T. T. ] , free testosterone [ F. T. ] , dehydroepi and rosterone-sulfate [ DHEA-S ] , delta-4- and rostenedione [ A. ] and sex hormone binding globulin [ SHBG ] ) , observations on the and rogen symptoms before treatment and their course during therapy were made . Moreover , the ratios of LH/FSH and E1/E2 as well as the and rogenic index , the ratio of total testosterone/SHBG were determined as control of treatment effects . The most important hormonal changes , which had been observed during a period up to two years are the following : --LH and FSH suppression -- prolactin with increasing tendency -- decrease of the total and rogens and free testosterone-- decrease of the oestrogens E1 , E2 - -increase of SHBG . The confirmation of the efficacy of the anti- and rogen/oestrogen combination was reflected by the decline of the and rogenic index in all groups . Acne and seborrhoe improved after 3 - 4 cycles ; alopecia after 8 - 9 cycles and hirsutism diminished after 3 cycles of treatment . In spite of different doses of the combined preparations with 2 mg cyproteronacetate and 0.035 or 0.050 mg ethinyloestradiol , no difference in ovarian suppression as well clinical effects could be found AIM This 12-month study was conducted to evaluate the skeletal effects of two monophasic oral contraceptives containing 20 mug of ethinylestradiol and 100 mug of levonorgestrel ( LEVO ) or 150 mug of desogestrel ( DESO ) . METHODS Fifty-two women ( 18 - 24 years ) were r and omized into the  DESO group or the LEVO group ; 36 women served as controls . The areal bone mineral density ( aBMD ) of the femoral neck and the lumbar spine was evaluated by DXA , and parameters of bone geometry and volumetric bone mineral density ( vBMD ) were assessed by peripheral quantitative computed tomography at the distal radius and the tibia . RESULTS The LEVO group did not lose vertebral aBMD , whereas women in the DESO group lost 1.5 % . At the distal radius and the tibia ( shank level , 14 % ) , LEVO induced an increase in total cross-sectional area , indicating increased periosteal bone formation . Radial trabecular vBMD declined by 1.4+/-1.8 % in the DESO group , while it remained unchanged in the LEVO group . CONCLUSION Our study suggests that the skeletal effects of OC preparations may be influenced by progestogenic components in young women A r and omised cross-over trial was performed to compare the pharmacodynamic actions of three low-dose oral contraceptives ( OCs ) : Marvelon  ( 150 micrograms desogestrel (DSG)+ 30 micrograms ethinyloestradiol ( EE ) ) , Mercilon ( 150 micrograms DSG + 20 micrograms EE ) and Microgynon ( 150 micrograms levonorgestrel ( LNG ) + 30 micrograms EE ) . None of the OCs produced any significant changes in serum cholesterol , LDL-C and apoprotein B. Triglycerides were increased by the desogestrel OCs but not by Microgynon . The latter however increased the glucose and insulin responses to a glucose tolerance test whereas Marvelon and Mercilon had no effect . HDL-C increased with Marvelon , was unchanged with Mercilon and was decreased with Microgynon . Apoprotein AII was increased by all three OCs but only the DSG OCs increased apoprotein AI . All OCs produced similar increases in caeruloplasmin but the increase in SHBG was much greater with Marvelon and Mercilon than with Microgynon . Testosterone was reduced more with Microgynon than with the DSG OCs . Many of the changes reflect the strong anti-oestrogenic action of LNG on metabolic parameters compared to DSG . Except for the effect on HDL-C , there was little difference between Marvelon and Mercilon on metabolic parameters and this complements the findings from large-scale clinical trials of the two OCs . Mercilon , therefore provides a very satisfactory alternative to Marvelon INTRODUCTION A new oral contraceptive containing the natural estrogen estradiol and a 19-nortestosterone derivate dienogest ( DNG ) in a four-phasic 28-day regimen may be used by women . AIM To investigate the quality of sexual life of healthy women on estradiol valerate and DNG ( E2V/DNG ) oral contraceptive . METHODS Fifty-seven women ( age range 18 - 48 years ) were enrolled . The Short Form-36 ( SF-36 ) question naire to assess quality of life ( QoL ) was administered at baseline and at the 26th day of both the 3rd and 6th cycles of oral contraceptive ( OC ) intake . The Short Personal Experience Question naire ( SPEQ ) to measure the change of sexual behavior was used at the 2nd , 7th , 14th , 21st , 26th , and 28th days of the baseline cycle , as well as at the same days of both the 3rd and 6th cycle of contraceptive intake . MAIN OUTCOME MEASURE The SF-36 and the SPEQ question naires . RESULTS Women reported QoL improvement at the 3rd ( P < 0.05 ) and at the 6th cycles ( P < 0.01 ) . By SPEQ , improvement of sexuality during the 3rd and the 6th cycle with respect to baseline experience was observed ( P < 0.05 ) . The frequency of sexual activity remained basically unchanged ( P = NS ) . Enjoyment and desire improved at the 6th cycle with respect to the 3rd cycle ( P < 0.05 ) . All women reported decreased dyspareunia at the 3rd and 6th cycles ( P < 0.05 ) . Interestingly , desire , arousal , orgasm , enjoyment , and sexual activity improved , reaching a peak around the 14th day of the menstrual cycle ( P < 0.05 ) . At the 3rd and 6th cycle , women on OCs were sexually cyclic , but the peak improvement of desire , arousal , orgasm , enjoyment , and sexual activity appeared around the 7th day of OC intake ( P < 0.05 ) . CONCLUSION Reduced hormone-free interval is a new concept in low-dose OC regimens . Moreover , the E2V/DNG multiphasic extended regimen has been found to positively modify the sexuality of users And rogen deficiency in women is increasingly recognized as a new clinical syndrome and has raised our awareness of the importance of accurate and well-vali date d measurements of serum free testosterone ( T ) concentrations in women . Therefore , we compared serum free T levels measured by equilibrium dialysis to those measured by a direct RIA ( analog method ) and to those calculated from the law of mass action ( requires the measurement of total T and SHBG ) . We also calculated the free and rogen index , 100 x T/SHBG , as a simple index known to correlate with free T. Subjects were 147 women with variable and rogen and estrogen statuses . All were studied three times in 1 month and included women 1 ) with regular menses ( estrogen positive , T positive ) , 2 ) more than 50 yr old and not receiving estrogen ( estrogen negative , T positive ) , 3 ) receiving estrogen ( estrogen positive , T negative ) , and 4 ) with severe and rogen deficiency secondary to hypopituitarism ( estrogen negative , T negative ) . Calculated values for free T using the laws of mass action correlated well with those obtained from equilibrium dialysis ( r = 0.99 ; P < 0.0001 ) . However , the agreement depended strongly on the specific assays used for total T and SHBG . In contrast , the direct RIA method had unacceptably high systematic bias and r and om variability and did not correlate as well with equilibrium dialysis values ( r = 0.81 ; P < 0.0001 ) . In addition , the lower limit of detection was higher for the direct RIA than for equilibrium dialysis or calculated free T. Free and rogen index correlates well with free T by equilibrium dialysis ( r = 0.93 ; P < 0.0001 ) , but is a unitless number without reference to the physical reality of free T. We conclude that the mass action equation and equilibrium dialysis are the preferred methods for use in diagnosing and rogen deficiency in women The pharmacokinetics of levonorgestrel ( LNG ) and ethinylestradiol ( EE2 ) were determined in 14 healthy women ( age 18 to 27 years ) during a treatment period of three months with a tri-step combination oral contraceptive ( Triquilar ) .  Prior to this treatment period , the same women received a single administration of a coated tablet containing 0.125 mg LNG together with 0.03 mg EE2 . There was a washout phase of one week between both treatments . Following single dose administration , a mean terminal half-life of 22 h was observed for LNG . The total clearance was 1.0 ml x min-1 x kg-1 and the volume of distribution was 128 l. During a treatment cycle , LNG levels in the serum accumulated by a factor of about four as compared to single dose administration . Steady-state drug levels were reached during the second half of each cycle . As compared to single dose administration , the following changes were observed for LNG at the end of treatment cycles one and three : reduced total ( 0.5 ml x min-1 x kg-1 ) and free clearance ( 50 ml x min-1 x kg-1 ) and a reduced volume of distribution ( 52 l ) . A concomitant increase in the SHBG concentrations by a factor of two as compared to pretreatment values was observed during treatment and appeared to be mainly responsible for the changes in the pharmacokinetics of LNG . Marked changes were also seen for the serum protein binding of LNG . After single dose administration , the free fraction of LNG was 1.4 % and the fractions bound to SHBG and albumin were 55.0 % and 43.6 % , respectively . At the end of cycle one , the free fraction was only 1.0 % and the fractions bound to SHBG and albumin were 69.4 % and 30.0 % , respectively . There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of LNG at the end of cycles one and three . On the last day of treatment cycles one and three , the AUC(0 - 4h ) values of EE2  were 331.2 and 369.6 pg x ml-1 x h , respectively , which corresponds to an about 11 - 24 % increase as compared to single dose administration , where an AUC(0 - 4h ) value of 298.3 pg x ml-1 x h was found . Total and free testosterone concentrations decreased during treatment cycles one and three by about 41 % and 55 % , respectively , compared with the corresponding values measured prior to treatment Changes in endogenous and rogen metabolism were compared in healthy women taking one of four low-dose modern oral contraceptives ( OCs ) . One hundred women were r and omized to ( 1 ) 35 micrograms ethinyl estradiol ( EE ) + 250 micrograms norgestimate ( Cilest ) ; ( 2 ) 20 micrograms EE + 150 micrograms desogestrel ( Mercilon ) ; ( 3 ) 30 micrograms EE + 150 micrograms desogestrel ( Marvelon ) ; or ( 4 ) 30 micrograms EE + 75 micrograms gestodene ( Femodene ) . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded , and plasma levels of the following variables were recorded : sex-hormone-binding globulin ( SHBG ) , cortisol-binding globulin ( CBG ) , testosterone , free testosterone , dihydrotestosterone , and rostenedione , dihydroepi and rosterone sulfate ( DHEAS ) , and hydroxyprogesterone . The free and rogen index was also calculated . These variables were remeasured during the third week of OC intake and during the fourth and sixth cycles . There were no statistically significant differences in and rogenic variables among the four OCs . The DHEAS concentration decreased less with the 20 micrograms EE + desogestrel formulation compared with either 30 micrograms EE + desogesterel or norgestimate-containing formulations ( 20 % vs. 45 % ) . Concentrations of SHBG and CBG increased significantly in all four groups ( average 263 + /- 119 % and 94 + /- 26 % , respectively ) ; CBG increased less in women taking 20 micrograms EE + desogestrel ( about 75 % ) than in the other formulations ( about 100 % ) . The four modern , low-dose OCs tested had similar impacts on endogenous and rogen metabolism , yielding significant decreases in testosterone , dihydrotestosterone , and rostenedione , and DHEAS . All of these formulations may be beneficial in women with and rogen-related syndromes such as acne and hirsutism . Large studies are under way to establish which of the third-generation OCs is the least and rogenic . In vitro studies suggest that norgestimate has the least and rogenic profile The aim of the present study was to compare changes in the endogenous and rogen environment in healthy women while on low-dose oral contraceptives ( OCs ) . One-hundred healthy women were r and omized to receive one of four OCs during six months : 21 tablets of Cilest , Femodeen , Marvelon , or Mercilon . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded and the following parameters were measured : sex hormone-binding globulin ( SHBG ) , corticosteroid-binding globulin ( CBG ) , testosterone ( T ) , free testosterone ( FT ) , 5 alpha-dihydrotestosterone ( DHT ) , and rostenedione ( A ) , dehydroepi and rosterone-sulphate ( DHEA-S ) and 17 alpha-hydroxyprogesterone ( 170HP ) while also the free and rogen index ( FAI ) was calculated . Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month . There were no differences on body mass and blood pressure with the use of the four OCs . The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon ( approximately 20 % vs 45 % ) . Mean serum SHBG and CBG increased significantly in all four groups approximately 250 % and 100 % , respectively . In each group CBG also increased significantly but less in women taking Mercilon ( -75 % ) as compared to the others ( -100 % ) . Current low-dose OCs were found to have similar impact on the endogenous and rogen metabolism with significant decreases of serum testosterone , DHT , A , and DHEA-S. They may be equally beneficial in women with and rogen related syndromes such as acne and hirsutism Circulating concentrations of sex hormone-binding globulin ( SHBG ) are increased by use of oral estrogen . The objective of this study was to determine whether postmenopausal women who used oral estrogen  had higher serum concentrations of SHBG and lower serum concentrations of free testosterone ( T ) than nonusers , and whether free T was associated with lean body mass , particularly skeletal muscle mass . Subjects were 70 postmenopausal women , 46 - 55 yr old , 46 of whom used oral estrogen .  Total and regional body composition were determined by dual-energy x-ray absorptiometry .  Serum concentrations of SHBG , total T , and estradiol ( E(2 ) ) were determined by RIA .  Free T was calculated from concentrations of total T and SHBG .  Hormone users had higher serum concentrations of E(2 ) and SHBG ( 182.0 + /- 58 . 5 vs. 82.9 + /- 41.1 nmol/L , mean + /- SD , P : < 0.001 ) and lower concentrations of free T ( 3.7 + /- 2.2 vs. 7.9 + /- 4.1 pmol/L , mean + /- SD , P : < 0.001 ) ; total T did not differ . Total lean mass and leg lean mass were significantly correlated with free , but not total T [ r values of 0.29 ( P : < 0.05 ) and 0.31 ( P : < 0.01 ) for total and leg lean mass , respectively , vs. free T ] ; arm lean mass was not correlated with either measure of T. Serum E(2 ) was significantly correlated with SHBG ( r = 0.50 , P : < 0.001 ) and free T ( r = -0.33 , P : < 0.01 ) . These observations imply that , by reducing the concentration of bioavailable T , oral estrogen therapy may accelerate or augment lean mass loss among postmenopausal women . This conclusion awaits confirmation by longitudinal observation OBJECTIVE RIA-based sex hormone measurements offer only limited precision and specificity in the low concentration range of women . Therefore , we aim ed to establish age-specific reference ranges for serum sex hormone concentrations in women using mass spectrometry and quantile regression . METHODS AND RESULTS Data from 985 women aged 20 - 80 yr , recruited for the prospect i ve Study of Health in Pomerania , were included in the analyses . Quantile regressions models were performed to calculate the age-specific 2.5th and 97.5th percentiles for sex hormone concentrations in women . Serum total testosterone ( TT ) and and rostenedione ( AD ) concentrations were measured by liquid chromatography-t and em mass spectrometry . Measured concentrations of SHBG and TT were used to calculate free testosterone ( free T ) . TT , AD , and free T concentrations showed a distinct age-related decline across 10-yr age groups ( one way ANOVA P < 0.001 ) . Sex hormone reference ranges for TT , AD , and free T were determined across each single year of age and for 10-yr age groups . Reference ranges over the whole age range of 20 - 80 yr were 0.35 - 1.97 nmol/liter for TT , 0.89 - 4.56 nmol/liter for AD , and 0.0025 - 0.0253 nmol/liter for free T. Separate reference ranges were provided for pre- and postmenopausal women as well as after inclusion of women using oral contraceptives or hormone therapy ( n = 1357 ) . CONCLUSION This is the first study to establish age-specific reference ranges for liquid chromatography-t and em mass spectrometry-measured  TT and AD and calculated free T concentrations based on quantile regression analyses , accurately accounting for the observed low concentration range and the strong age dependency of these sex hormones in women BACKGROUND This study was conducted to compare the effects of two contraceptive pills with different doses of the same components , on plasma and rogen levels and female sexual function among women without previous sexual dysfunction .  STUDY DESIGN The participants were r and omized into two groups , to receive pills containing ethynylestradiol ( EE ) 30 mcg and levonorgestrel ( LNG ) 150 mcg or EE 20 mcg and LNG 100 mcg , for six cycles . Sexual function was assessed using a st and ardized question naire [ Female Sexual Function Index ( FSFI ) ] . Hormone assays were performed at baseline and after the sixth cycle . RESULTS Forty-nine women were included in the EE30/LNG150 group and 48 in the EE20/LNG100 group .  EE30/LNG150 group presented 54 % and 67 % decreases of total testosterone and free and rogen index , respectively , with statistical significance . EE20/LNG100 presented reductions of 20 % and 42 % , respectively , but without statistical significance . Both groups showed improvements in the FSFI " desire " score , but with statistical significance only for EE20/LNG100 group . CONCLUSIONS EE30/LNG150 decreased plasma and rogen levels , but there was no impairment in sexual desire , on the other h and , sexual desire score increased with EE20/LNG100 formulation OBJECTIVE The purpose of this study was to compare biochemical and rogen profiles in women treated with the contraceptive patch versus an oral contraceptive ( OC ) . STUDY DESIGN Twenty-four healthy women were r and omly assigned to receive 3 cycles of either the contraceptive patch ( ethinyl estradiol [ EE ] 20 microg/d and norelgestromin 150 microg/d ) or OC ( EE 35 mug and norgestimate 250 microg ) . Blood sample s were taken at baseline and end of treatment . Serum levels of sex hormone-binding globulin ( SHBG ) , total testosterone ( T ) , and rostenedione ( A ) , dehydroepi and rosterone sulfate ( DHEAS ) , dihydrotestosterone ( DHT ) , and 3alpha- and rostanediol glucuronide ( 3alpha-diol G ) were quantified by immunoassay methods ; free T was calculated . The paired t and Student t tests were used for statistical analysis . RESULTS Nineteen women completed the study ( patch , n = 10 ; OC , n = 9 ) . Despite a 1.6-fold relative increase in SHBG levels with the patch versus OC ( 449 % vs 274 % , P = .03 ) , free T decreased equally in both groups ( patch 60 % , P < .0001 ; OC 59 % , P < .0001 ) . DHEAS decreased by 26 % in the patch group ( P < .01 ) and 32 % in the OC group ( P < .001 ) . 3alpha-diol G was reduced by 52 % in the patch group ( P < .0001 ) and 51 % in the OC group ( P < .0001 ) . In addition , the OC was associated with significant decreases in A and DHT . CONCLUSION The contraceptive patch had an effect comparable to the OC on several key and rogenic markers . Given these biochemical findings , the contraceptive patch has significant potential as a therapeutic agent for disorders of and rogen excess CONTEXT There is no st and ardized assay of testosterone in women .  Liquid chromatography mass spectrometry ( LC/MS ) has been proposed as the preferable assay by an Endocrine Society Position Statement . OBJECTIVE The aim was to compare assay results from a direct RIA with two LC/MS . DESIGN AND SETTING We conducted a blinded laboratory study including masked duplicate sample s at three laboratories -- two academic ( University of Virginia , RIA ; and Mayo Clinic , LC/MS ) and one commercial ( Quest , LC/MS ) . PARTICIPANTS AND INTERVENTIONS Baseline testosterone levels from 596 women with PCOS who participated in a large , multicenter , r and omized controlled infertility trial performed at academic health centers in the United States were run by varying assays , and results were compared . MAIN OUTCOME MEASURE We measured assay precision and correlation and baseline Ferriman-Gallwey hirsutism scores . RESULTS Median testosterone levels were highest with RIA . The correlations between the blinded sample s that were run in duplicate were comparable . The correlation coefficient ( CC ) between LC/MS at Quest and Mayo was 0.83 [ 95 % confidence interval ( CI ) , 0.80 - 0.85 ] , between RIA and LC/MS at Mayo was 0.79 ( 95 % CI , 0.76 - 0.82 ) , and between RIA and LC/MS at Quest was 0.67 ( 95 % CI , 0.63 - 0.72 ) . Interassay variation was highest at the lower levels of total testosterone ( ≤50 ng/dl ) . The CC for Quest LC/MS was significantly different from those derived from the other assays . We found similar correlations between total testosterone levels and hirsutism score with the RIA ( CC=0.24 ) , LC/MS at Mayo ( CC=0.15 ) , or Quest ( CC=0.17 ) . CONCLUSIONS A testosterone RIA is comparable to LC/MS assays . There is significant variability between LC/MS assays and poor precision with all assays at low testosterone levels The effects of the oral contraceptive combinations 0.125 mg Org 2969 ( desogestrel ) ( 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-17-ol ) + 0.05 mg ethinyloestradiol ( EE ) and 0.125 mg levonorgestrel + 0.05 mg EE on serum sex-hormone-binding globulin ( SHBG ) , ceruloplasmin , transcortin and ratio free testosterone over total testosterone ( percentage free testosterone ) and ratio free 5alpha-dihydrotestosterone over total 5alpha-dihydrotestosterone ( percentage free 5alpha-dihydrotestosterone ) were compared in healthy female volunteers . Treatment was r and omly distributed over the volunteers ; 11 women received  Org 2969 + EE  and 11 women received  levonorgestrel + EE . These combinations induced similar increases in transcortin levels ( 115 and 140 % ) and ceruloplasmin levels ( 115 and 123 % ) after 3 months of treatment . However , the combination Org 2969 + EE induced a substantial increase ( 213 % ) in SHBG capacity after 3 months of treatment , whereas a smaller increase ( 80 % ) was observed with levonorgestrel + EE . A return to pretreatment values was observed 2 months after termination of treatment for all parameters . The difference in the effects of both preparations oh SHBG was statistically significant and can be best explained by a difference in the and rogenicity of the progestogens . A good correlation was free testosterone and the reciprocal value of the percentage free 5 alpha-dihydrotestosterone . These results confirm that SHBG is the major regulator of the biologically active free and rogen fraction in women before , during and after combined oral contraceptive treatment In a double-blind , controlled , r and omized , four-arm , bicentric clinical study , the effect of four oral contraceptives ( OCs ) on various hormone parameters and serum-binding globulins was investigated . Four groups with 25 volunteers each ( 18 - 35 years of age ) were treated for six cycles with monophasic combinations containing 21 tablets with either 30 microg ethinylestradiol ( EE ) + 2 mg dienogest ( DNG ) ( 30EE/DNG ) , 20 microg EE + 2 mg DNG ( 20EE/DNG ) , 10 microg EE + 2 mg estradiol valerate ( EV ) + 2 mg DNG ( EE/EV/DNG ) or 20 microg EE + 100 microg levonorgestrel ( LNG ) ( EE/LNG ) . The study was completed by 91 subjects . Blood sample s were taken after at least 12 h of fasting on Day 21 - 26 of the preceding control cycle and on Day 18 - 21 of the first , third and sixth treatment cycle . The serum concentrations of free testosterone were significantly decreased by about 40 - 60 % in all four groups , while those of dehydroepi and rosterone sulfate ( DHEAS ) showed a time-dependent decrease during treatment . Except for EE/EV/DNG , which increased prolactin significantly during the third and sixth cycles , no change was observed with the EE-containing preparations . There was a significant increase in the levels of serum-binding globulins during treatment , which differed according to the composition of the OCs used . The rise in sex hormone-binding globulin ( SHBG ) was highest during intake of 30EE/DNG ( + 320 % ) and lowest with EE/LNG ( + 80 % ) , while the effect of 20EE/DNG and EE/EV/DNG was similar ( + 270 % ) . The thyroxine-binding globulin ( TBG ) levels increased significantly , by 50 - 60 % , during treatment with the DNG-containing formulations , while the effect of EE/LNG was less significant ( + 30 % ) . The rise in corticosteroid-binding globulin ( CBG ) , which occurred in all groups , was most pronounced in women treated with 30EE/DNG ( + 90 % ) and least with EE/EV/DNG ( + 55 % ) , indicating a strong influence of EE and no effect of the progestogen component . In all treatment groups , the frequency of intracyclic bleeding rose in the first treatment cycle and decreased thereafter . Cycle control was significantly better with 30EE/DNG or EE/LNG than with 20EE/DNG or EE/EV/DNG . There was no significant change in blood pressure , body mass index or pulse rate throughout the study . In conclusion , the DNG-containing OCs caused a higher rise in SHBG and TBG levels than the LNG-containing preparation . The effects on CBG suggest a lesser hepatic effect of 2 mg EV as compared to 20 or 30 microg EE . In contrast to EE , the use of estradiol in OCs appeared to increase prolactin release , while the cycle control was better with the OC containing 30 microg EE ABSTRACT Objectives To compare the effects of two monophasic combined oral contraceptives , containing either nomegestrol acetate/17β-oestradiol ( NOMAC/E2 ) or levonorgestrel/ ethinylestradiol ( LNG/EE ) on endocrine function , and rogens , and sex hormone-binding globulin ( SHBG ) . Methods R and omised , open-label , multi-centre trial involving 121 healthy women , aged 18–50 years old . Participants received NOMAC/E2 ( 2.5 mg/1.5 mg ) in a 24/4-day regimen ( n = 60 ) or LNG/EE ( 150 μg/30 μg ) in a 21/7-day regimen ( n = 61 ) for six cycles . The primary outcome was the change from baseline to cycle 6 in markers of adrenal and thyroid function , and rogens , and SHBG . Results Total cortisol , corticosteroid-binding globulin ( CBG ) , and thyroxine-binding globulin ( TBG ) increased from baseline in both groups , with significantly greater increases in the LNG/EE group . No relevant changes from baseline or differences between the groups were observed for thyroid-stimulating hormone ( TSH ) and free thyroxine ( T4 ) . And rogens and and rogen precursors decreased from baseline in both groups , with significantly greater decreases in the LNG/EE group ( except for free testosterone ) . A greater increase in SHBG was observed with NOMAC/E2 than with LNG/EE . Conclusions NOMAC/E2 has significantly less influence on markers of adrenal and thyroid function and and rogens than LNG/EE . The clinical relevance of these findings requires further study In this study , we vali date d measurements of free testosterone ( fT ) and free estradiol ( fE(2 ) ) concentrations calculated from total serum concentrations of testosterone ( T ) , estradiol ( E(2 ) ) , and sex hormone-binding globulin ( SHBG ) , measured by direct , commercial radioimmunoassays , by comparison with reference measurements obtained by dialysis plus an in-house radioimmunoassay after extraction and chromatographic purification . The study was conducted in serum sample s from 19 postmenopausal women who were part of an ongoing prospect i ve cohort study . We also performed sensitivity analyses to examine the robustness of the theoretical calculations . Sensitivity analyses showed that in this population , competitive binding of dihydrotestosterone and total T could be ignored in the calculation of fE(2 ) , and competitive binding by dihydrotestosterone does not need to be taken into account for calculation of fT. Furthermore , variations in albumin and SHBG concentrations had negligible effects on fT and fE(2 ) calculations . Values of fT and fE(2 ) , calculated from total T and E(2 ) concentrations obtained by the same in-house radioimmunoassay used for the dialysis method , correlated highly with the measurements by dialysis ( Pearson 's coefficients of correlation above 0.97 ) . When calculating fT and fE(2 ) using total T and total E(2 ) concentrations obtained by different direct radioimmunoassays , almost all kits gave good correlations with the reference method for fT ( Pearson 's r > 0.83 ) , but only a few gave good correlations for fE(2 ) ( Diagnostic System Laboratories and DiaSorin ; r > 0.80 ) . The direct radioimmunoassays giving the best correlation for fT and fE(2 ) with the dialysis method were those that best measured total concentrations of T and E(2 ) . Furthermore , mean values of fT and fE(2 ) corresponded well to mean values by the reference method if SHBG measurements were also well calibrated . We conclude that in postmenopausal women , theoretical calculations are valid for the determination of fT and fE(2 ) concentrations and can give reliable estimation of cancer risk in epidemiological studies when the total concentrations of T , E(2 ) , and SHBG are measured accurately Twenty-six healthy , non-hirsute women had antecubital venous blood obtained before and during treatment with various  contraceptive steroids  for the measurement of dehydroepi and rosterone sulfate ( DHEA-S ) .  Six of the women were r and omized to receive Ortho Novum 1/35 ( O/N ) , 7 were assigned to Ovcon 35 ( OV ) , and another five received Nordette ( N ) . The 6 women ingesting O/N as well as the 7 receiving OV had significant decreases in serum concentrations of DHEA-S ( p less than 0.05 ) . The percentage of decrease in DHEA-S in the O/N group ( 39 + /- 6 % ) and in the OV group ( 30 + /- 5 % ) was not statistically different . The group receiving N showed no changes from baseline measurements . Serum sample s from another 8 women who had received subcutaneous implants of levonorgestrel ( 1-Ng ) were obtained . No significant changes occurred in serum DHEA-S between baseline and six-month sample s. The data that 1-Ng alone and the combination of 1-Ng and ethinylestradiol did not change DHEA-S levels suggest that 1-Ng does not affect adrenal and rogen secretion . Because N , O/N and OV contain similar quantities of ethinylestradiol , these results indicate that norethindrone , but not 1-Ng , has a major suppressive effect upon adrenal and rogen secretion Anti and rogens or progestins with an anti and rogenic component usually have only a weak antigonadotropic activity . It is thus possible that the anti and rogenic effect on the cellular level is cancelled or at least reduced by an increased ovarian and rogen production . The aim of the four su bmi tted clinical studies of the progestin and anti and rogen dienogest alone ( 0.5 - 2 mg/day ) or of a combined regimen of ethinylestradiol ( 0.03 mg ) plus dienogest ( 2 mg ) ( EE/DNG ) was to examine the influence on the serum and rogen and SHBG concentrations as well as on the serum FSH , LH , progesterone and 17 beta-estradiol concentrations in young women . Like the progesterone derivatives , dienogest has a relatively low antigonadotropic activity . Inhibition of ovulation is mainly produced by peripheral mechanisms such as the reduction of preovulatory 17 beta-estradiol secretion .  Dienogest alone has no significant effects on the serum SHBG and and rogen concentrations . Unlike this , the combination of EE plus DNG markedly increases SHBG concentrations ( to 2.1 - 3.7 fold the basal levels ) . The decrease in serum and rogens with total testosterone ( by 17 and 40 % ) , free testosterone ( by 48 and 54 % ) and dehydroepi and rosterone sulfate ( by 51 % ) corresponds to the values shown in the literature for other oral contraceptives with modern progestins . EE/DNG does not affect the serum concentrations of 5 alpha-dihydrotestosterone ( DHT ) , although the marker of the peripheral transformation from T to DHT , and rostanediol glucuronide , is distinctly reduced ( by 38 % ) . In a double-blind comparison no differences are found between EE/DNG and a regimen combining 0.02 mg of ethinylestradiol and 0.150 mg of desogestrel . Solely the SHBG concentrations , with EE/DNG , as expected , are significantly higher . In a sequential regimen , dienogest , chlormadinone acetate and desogestrel ( progestins without binding to SHBG ) enhance the inhibitory effect of ethinylestradiol sulfonate on free testosterone , whereas norethindrone acetate and levonorgestrel ( progestins with a strong binding to SHBG ) reduce this effect of the estrogen significantly . These results exclude the possibility that the very distinct anti and rogenic effect of dienogest on a cellular level is neutralised or reduced by an increased systemic supply of and rogen The effectiveness of a low-dose oral contraceptive ( OC ) in suppressing plasma levels of gonadotropins , ovarian , and adrenal and rogens and stimulating sex hormone-binding globulin ( SHBG ) was evaluated prospect ively in nonhirsute women . Thirty-three women ingested 35 micrograms of ethinyl estradiol and 1 mg of norethindrone beginning within day 1 to 5 of the menstrual cycle . Baseline levels of luteinizing hormone , follicle-stimulating hormone , total testosterone ( T ) , and rostenedione ( A ) , dehydroepi and rosterone sulfate ( DHEAS ) , and SHBG were obtained before ingestion of the OC and repeated after 3 , 6 and , 9 months of OC use on day 1 to 5 of the OC " cycle " . A significant suppression of gonadotropin levels is seen in nonhirsute women .  Sex hormone binding globulin is consistently stimulated by the low-dose OC . A significant suppression of T and DHEAS is observed . No change was seen in levels of A. The demonstrated effects become evident at 3 months and are maintained at 6 and 9 months Twenty women using oral contraceptives and complaining of impaired sexual function were compared with twenty women without sexual problems , matched for age and oral contraceptive . Whilst the sexual behaviour differed in the two groups , the plasma testosterone , and rostenedione , oestradiol and SHBG concentrations were very similar . The total and rogen levels were low in both groups . Plasma testosterone and oestradiol concentrations were correlated with measures of sexual interest in the no‐problem group , but not in the problem group . Administration of exogenous and rostenedione to women in the problem group , using a double blind cross‐over comparison with a placebo , failed to improve their sexual function except in one case . The majority of women showed a rise in and rogen and oestradiol between day 24 of one pill cycle and day 4 of the next . The possible behavioural indications of this pattern are discussed Two triphasic oral contraceptives containing gestodene ( GES ) ( a new progestogen ) and levonorgestrel ( LNG ) were compared with respect to contraceptive effect , cycle control , acceptability and side effects . The serum concentrations of ingested hormones were measured together with ovarian , pituitary , and some adrenal hormones , as well as sex hormone binding globulin ( SHBG ) . The contraceptive effect and cycle control were good with both preparations , and there were only a few minor side effects . SHBG was elevated 2-fold in the LNG group and 3-fold in the GES group . The  GES concentration in serum varied more than the LNG concentration , but with correction for variations in SHBG binding , less variability in actual GES and LNG concentrations was seen . Serum levels of FSH , LH , estradiol and progesterone were all depressed with both preparations . The depression was more marked in the GES group , despite lower progestogen ingestion and similar serum concentrations . Equal decreases were found in testosterone , and rostenedione and dehydroepi and rosterone sulfate ( DHEA-S ) with both preparations The study was performed in 14 young women . The combination oral contraceptive contained 75 μg gestodene ( GSD ) and 20 μg ethinyl estradiol ( EE2 ) per dosage unit . The volunteers received a single dose on day 21 of a treatment-free precycle ( PCd21 ) and , after a washout period of 7 days , used the preparation in a 21 d/7 d schedule for three months . Daily drug serum level profiles were taken on PCd21 and on days 1 and 21 of treatment cycles 1 and 3 . In addition , trough drug serum levels were followed every other day during treatment cycles 1 and 3 . Serum levels of GSD , EE2 , CBG , SHBG and testosterone ( T ) were determined by means of specifically developed or commercially available RIAs . Pharmacokinetic evaluation was carried out with TOPFIT and parameters were evaluated for differences with thet-test . Main target variables wereCmax , tmax and AUC for EE2 , GSD and unbound GSD on day 21 , cycle 3 vs. PCd21.EE2 pharmacokinetics were in agreement with a dose of 20 μg/unit . Single-doseCmax of 65 pg/ml and AUC of 612 pg h ml−1 increased by 40–60 % during treatment cycles as a result of accumulation  . EE2 induced basal SHBG ( 102 nmol/L ) and CBG ( 42 μg/ml ) serum levels to about 220 nmol/L and 87 μg/ml , respectively , at the end of treatment cycles 1 and 3.Serum T levels dropped to 50 % of baseline levels during treatment cycles and free T concentrations were reduced by 60–70 % . GSD  pharmacokinetics at the end of treatment cycles 1 and 3 were different from single-dose pharmacokinetics . Single-doseCmax of 3.5 ng/ml and AUC0–24 h of 22 ng h ml−1 increased to steady-state levels of 8–8.7 ng/ml and 90–106 ng h ml−1 , respectively . The increase in GSD levels under treatment is the result of two parallel processes , i.e. accumulation and enlargement of the specific binding compartment . This was shown by protein-binding experiments , demonstrating an increase in specific ( SHBG ) binding from 69 % to 80 % and a reduction in the free fraction of GSD by 40 % during treatment . The results of GSD and EE2  pharmacokinetics obtained in the present study confirm previous results with Femodene , when the reduction in the EE2 dose by 10 μg/d is taken into account . ResuméCette étude a été réalisée sur 14 jeunes femmes . Le contraceptif oral combiné contenait 75 μg de gestodène ( GSD ) et 20 μg d'éthinyl oestradiol ( EE2 ) par dose unitaire . Les volontaires ont reçu une dose unique au vingt et unième jour du cycle préliminaire sans traitement ( CPj21 ) et — après une période de 7 jours de sevrage — elles ont absorbé la préparation selon une posologie de 2lj/7j pendant trois mois . Les profils journaliers du taux sérique du produit ont été établis au jour CPj21 et aux jours 1 et 21 des cycles de traitement 1 et 3 . En outre , on a suivi tous les deux jours , durant les cycles 1 et 3 du traitment , les taux sériques inférieurs du produit . On a déterminé , selon des méthodes de RIA spécifiquement mises au point ou commercialement disponibles , les taux sériques de GSD , EE2 , CBG , SHBG et testostérone ( T ) . L'évaluation pharmacocinétique a été exécutée à l'aide du TOPFIT et les paramètres ont été évalués en vue de déterminer les différences avec les résultats du test-t . Les principales variables ciblées étaient lesCmax , tmax et ASC pour l'éthinyl oestradiol , GSD et GSD non lié , au jour 21 du cycle 3 par rapport au CPj21.La pharmacocinétique de l'EE2 correspondait à une dose de 20 μg/unité . LeCmax d'une dose unique de 65 pg/ml et l'ASC de 612 pg h ml−1 augmentaient de 40 à 60 % durant les cycles de traitement par suite d'accumulation . L'EE2 induisait des taux sériques de SHBG de base ( 102 nmol/l ) et de CBG ( 42 μg/ml ) d'environ 220 nmol/l et 87 μl/ml respectivement à la fin des premier et troisième cycles . Les taux sériques de T tombaient à 50 % des niveaux de base durant les cycles de traitement et les concentrations de T libre étaient réduites de 60 à 70 % . La pharmacocinétique du GSD à la fin des cycles de traitement 1 et 3 était différente de celle d'une dose unique . LesCmax d'une dose unique de 3,5 ng/ml et l'ASC0–24h de 22 ng h ml−1 augmentaient jusqu'à des niveaux stables de δ-8,7 ng/ml et 90–106 ng h ml−1 respectivement . La hausse des taux de GSD durant le traitement résulte de deux processus parallèles : accumulation et élargissement du compartiment spécifiquement liant . Ce fait est démontré par des expériences de liaison des protéines , lesquelles indiquent une liaison spécifique accrue ( SHBG ) , passant de 69 à 80 % et une réduction de la fraction libre de GSD de 40 % au cours du traitement . Les résultats de la pharmacocinétique du GSD et de l'EE2  obtenus dans la présente étude confirment ceux obtenus précédemment avec le Femodene , lorsque la réduction de 10 μg/j de la dose de EE2 est prise en compte . ResumenEste estudio se realizó con 14 mujeres jóvenes . La combinación de anticonceptivos orales contenía 75 μg de gestodén ( GDS ) y 20 μg de etinil estradiol ( EE2 ) por unidad de dosificación . Las voluntarias recibieron una sola dosis en el vigésimo primer día de un preciclo sin tratamiento ( PCd21 ) y , después de un período de interrupción de siete días — utilizaron la preparación al séptimo día de un programa de 21 días durante tres meses . Se obtuvieron perfiles diarios del nivel sérico de los fármacos en el PCd21 y en los días 1 y 21 de los ciclos del primer y tercer ciclo de tratamiento . Además , se realizó el seguimiento de los niveles séricos mínimos de los fármacos cada dos días durante el primer y tercer ciclo de tratamiento . Los niveles séricos de GSD , EE2 , CBG , SHBG y testosterona ( T ) se determinaron mediante RIA específicamente desarrollados o comercialmente disponibles . La evaluación farmacocinética se realizó con TOPFIT y se evaluaron las diferencias de los parámetros con el test-t . Las principales variables a determinar fueronCmáx , tmáx y AUC para EE2 , GSD  y GSD no ligado al vigésimo primer día del tercer ciclo en comparación con PCd21.La farmacocinética de EE2 guardaba conformidad con una dosis de 20 μg/unidad . LaCmáx de dosis única de 65 pg/ml y AUC de 612 pg h ml−1 aumentó en un 40–60 % durante los ciclos de tratamiento debido a la acumulación . EE2 indujo niveles séricos de SHBG basal ( 102 nmol/l ) y CBG ( 42 μg/ml ) de aproximadamente 220 nmol/l y 87 μg/ml , respectivamente , al final del primer y tercer ciclo de tratamiento . Los niveles séricos de T se redujeron al 50 % de los niveles de línea de referencia durante los ciclos de tratamiento y las concentraciones de T libre se redujeron en un 60–70 % . La farmacocinética del GSD al concluir el primer y tercer ciclo de tratamiento fue diferente de la correspondiente a la dosis única . LaCmáx de dosis única de 3,5 ng/ml y AUC0–24h de 22 ng h ml−1 aumentó a niveles de estado estable de 8–8,7 ng/ml y 90–106 ng h ml−1 , respectivamente . El aumento de los niveles de GSD con el tratamiento se debe a dos procesos paralelos , es decir , acumulación y ampliación del compartimiento específico de ligazón . Esto se demostró mediante experimentos de ligazón de proteínas , que señalaron un aumento de la ligazón específica ( SHBG ) del 69 % al 80 % y una reducción de la fracción libre de GSD en un 40 % durante el tratamiento . Los result ados de la farmacocinética de GSD y EE2  obtenidos en el presente estudio confirman result ados anteriores con Femodene , al tenerse en cuenta la reducción de la dosis de EE2  en 10 μg/d The effect of seven low-dose oral contraceptive preparations on sex hormone binding globulin ( SHBG ) , cortisol binding globulin ( CBG ) , total and absolute free testosterone were investigated in groups of 10 healthy volunteers . All preparations contained about the same amount of ethinylestradiol but they differed in type and /or dose of progestagen . The progestagens studied were : levonorgestrel ( LNG ; in mono- and triphasic preparations ) , norethisterone ( NET ; in monophasic preparation ) , desogestrel ( DSG ; in mono- and biphasic preparations ) and gestodene ( GSD ; in triphasic preparation ) , all 19-nortestosterone derivatives , and the anti- and rogen cyproterone acetate ( CPA ) in a monophasic preparation . Differences observed in SHBG level , which reflect the estrogen- and rogen balance , can be attributed to the intrinsic and rogenic ( or anti- and rogenic ) properties of the progestagens , and were in agreement with the results of published receptor binding studies , performed in vitro . Based on our results the following ranking ( high to low ) can be made with respect to the and rogenicity of the preparations : monophasic LNG greater than or equal to monophasic NET = triphasic LNG greater than or equal to triphasic GSD = biphasic DSG = monophasic DSG greater than monophasic CPA . An anti-estrogenic effect of the 19-nortestosterone derived progestagens can be excluded by the effect on CBG , a marker for estrogenic activity . All preparations containing a 19-nortestosterone derived progestagen , independent of their type and dose , induce a similar rise in CBG , whereas the preparation with cyproterone acetate induced an even higher CBG level . Irrespective of the effect on total testosterone , which varies between the preparations , the absolute free testosterone level decreased to a comparable degree for all preparations . ( ABSTRACT TRUNCATED AT 250 WORDS In young women , low estrogen levels complicate a wide variety of diseases , including premature ovarian failure , anorexia nervosa , athletic amenorrhea , prolactinoma , hypopituitarism , and chronic kidney disease . Hypoestrogenemia may also result from therapy with GnRH agonists , glucocorticosteroids , chemotherapy , and especially aromatase inhibitors . All of these situations are associated with bone loss , because estrogen chronically suppresses bone resorption . Several mechanisms are involved : 1 ) estrogen increases osteoclast apoptosis ; 2 ) by suppressing interleukins and proinflammatory cytokine expression in bone marrow cells , estrogen decreases the number of osteoclasts ; 3 ) by inhibiting the production of receptor activator of nuclear factor-κB lig and , estrogen reduces the number and activity of osteoclasts ; and 4 ) by increasing stromal cell/osteoblast cell expression of TGFβ , estrogen inhibits osteoclast activity . Estrogen also has some positive effects on bone formation by acting as a mitogen to cells early in the osteoblast line , reducing apoptosis of osteoblasts , and increasing expression of TGFβ , bone morphogenetic proteins , and IGF-I ( 1 ) . In these pathological conditions , the cause of the bone loss is frequently multifactorial . For example , women with anorexia nervosa also have low IGF levels . Nonspecific factors such as poor diet , reduced exercise , or chronic inflammation may further increase bone resorption . Low estrogen levels are also seen in healthy young women who are using depo-medroxyprogesterone acetate ( DMPA ) for contraception .  Bone loss is a side effect of this medication ( 2 ) . The bone mineral density ( BMD ) decreases at a more rapid rate during the first years of therapy and then continues to decrease at a slower rate ( 3 ) . After 5 yr , the loss is about 6 % ( 0.5 sd ) . The  DMPA effects are worse in teenagers ; combined results from four prospect i ve studies found an average loss of spine BMD of 3.1 % over 2 yr in  DMPA  users compared with a gain of 7.2 % in untreated controls ( 4 ) . A cross-sectional study in this issue by Walsh and colleagues ( 5 ) focused on the age of starting DMPA .  One group aged 18–25 started DMPA before age 20 , and another group aged 35–45 started after age 34 . Each group had matched controls . Importantly , the average use was 37 months in both groups . This avoids the confounding between age and duration of use , which is encountered in other studies . The BMD was significantly lower than controls when DMPA was started in teenagers but not when it was started after age 34 . Estrogen levels were lower in the DMPA users than the non-hormone users and were also lower in the younger women than in the older women . The authors concluded that estrogen levels mediated the effect of DMPA on bone markers because adding DMPA to a regression model reduced the correlation between markers and estrogen . These correlations were not very strong ( r = −0.17 between N-telopeptide and estradiol-treated ) , so this is a tenuous conclusion , but it is bolstered by the findings from two other studies that adding estrogen to DMPA abolishes the negative effect on the skeleton ( 6,7 ) . The age range of the older group of women is underrepresented in most of the previous studies of skeletal effects of DMPA . These results lead to several questions about basic bone biology . How are adolescent bones different from mature bones ? How does DMPA use compare to the natural state of low estrogen seen in healthy lactating women ? Is bone completely restored in these situations ? There are also important clinical questions about potential risk of fractures and the skeletal risks from other forms of contraception The effect of two triphasic oral contraceptives ( Triquilar [ TRQ ] and Trisiston [ TRS ] ) containing ethinyl estradiol ( EE ) and levonorgestrel ( LNG ) on various hormonal parameters was investigated in 26 women during a cross-over study .  TRS consisted of 0.03 mg EE + 0.05 mg LNG ( six tablets ) , 0.04 mg EE + 0.075 mg LNG ( six tablets ) , and 0.03 mg EE + 0.15 mg LNG ( nine tablets ) , whereas TRQ was different in the second phase ( five tablets ) and third phase ( 10 tablets ) . Blood sample s were taken on days 6 , 11 , 21 , and 28 of the control and washout cycles and the third treatment cycle . Both formulations inhibited ovulation reliably and decreased the serum levels of gonadotropins , free testosterone , and dehydroepi and osterone sulfate in a time-dependent manner , whereas estradiol and testosterone were already suppressed on day 6 , indicating a direct suppressive effect on ovarian steroid synthesis . Prolactin , which rose sporadically in some women , was not significantly changed . In contrast , the levels of sex hormone binding globulin , corticosteroid binding globulin , and cortisol were significantly elevated by 100 % . During the hormone-free interval of 7 days , all parameters returned at least partly to baseline . There was no significant difference between the effects of both formulations . The results suggest the possibility of a direct inhibitory effect of contraceptive steroids on ovarian steroid synthesis Twenty-four healthy female volunteers with normal ovulatory cycles , aged between 20 and 34 years ( 27.5 + /- 4.3 ) , were included in a single-center , non-comparative study to investigate the effect on inhibition of ovulation of an oral contraceptive containing 20 micrograms ethinylestradiol in combination with 100 micrograms levonorgestrel . At baseline , during three treatment cycles and post-treatment , ultrasonography was used to examine the ovaries , to measure follicular size , and to measure the thickness of the endometrium . Serum levels of LH , FSH , estradiol , progesterone , total testosterone , free testosterone , SHBG , and CBG were also measured . Compared with treatment cycle 1 , an increase in residual ovarian activity ( follicle grade s 4 - 5 ) was observed in cycles 2 and 3 . Mean levels of LH , FSH , 17 beta-estradiol and progesterone remained suppressed during treatment . No escape ovulation was observed during the treatment phase of the study and there were no pregnancies . Ovulation was noted to return rapidly in the posttreatment cycle . Subjective and objective tolerance of the present regimen was noted to be good . Results indicate that the monophasic oral contraceptive containing 100 micrograms levonorgestrel combined with 20 micrograms ethinylestradiol effectively inhibits ovulation , providing adequate suppression of ovarian activity The effect of a triphasic oral contraceptive containing ethinylestradiol and gestodene ( EE/GSD ) on various serum hormonal parameters was compared with that of a monophasic formulation containing 35 micrograms ethinylestradiol and 250 micrograms norgestimate ( EE/NGM ) . Blood sample s were collected from 46 women on days 2 , 11 , and 21 of the preceding control cycle and of the third , sixth and twelfth treatment cycle . There was no significant difference in the influence on any hormonal parameter between both formulations . Both EE/GSD and EE/NGM caused a time-dependent suppression of serum dehydroepi and rosterone sulphate ( DHEA-S ) by 20 - 30 % ( p < 0.01 ) and a reduction of 5 alpha- and rostane-3 alpha , 17 beta-diol glucuronide by 50 - 60 % ( p < 0.01 ) during each treatment cycle , while and rostenedione levels were reduced by 25 % ( p < 0.01 ) . There was also a significant decrease in the levels of total testosterone by 30 - 35 % ( p < 0.01 ) and free testosterone by 60 % ( p < 0.01 ) , while sex hormone-binding globulin ( SHBG ) was increased by 200 - 240 % on days 11 and 21 ( p < 0.01 ) . During the pill-free interval the SHBG levels were reduced to a certain degree but remained elevated by 100 % as compared to the pretreatment values . The serum levels of corticosteroid-binding globulin ( CBG ) which is known to be influenced only by the estrogenic component of combination pills , increased significantly by 170 % ( p < 0.01 ) during each treatment cycle . During the pill-free interval of 7 days , the CBG levels decreased but were still elevated by 90 - 100 % as compared to the control cycle . Similarly , the serum levels of cortisol were significantly elevated by 110 - 140 % ( p < 0.01 ) during treatment with both preparations . The results demonstrate a profound suppression of and rogen levels and peripheral and rogen metabolism BACKGROUND This study was conducted to investigate the effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and and rogen parameters . STUDY DESIGN Thyroid and and rogen parameters were measured in 59 women treated with a monophasic combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest ( EE/DNG ) either conventionally ( 13 cycles with 21 days of treatment+7 days without hormones ) or according to an extended-cycle regimen ( four extended cycles with 84 days of continuous administration of  EE/DNG  , followed by a hormone-free interval of 7 days ) .  Blood sample s were taken on Days 21 - 26 of the preceding control cycle and on Days 19 - 21 of the 3rd and 13th conventional cycle , or on Days 82 - 84 of the first and fourth extended cycle . RESULTS At both time points , the serum concentrations of thyroxine-binding globulin were elevated by about 65 % in both treatment regimens . Likewise , both groups showed an increase in total triiodothyronine ( T3 ) and total thyroxine ( T4 ) by 30 - 40 % , and no change in free T4 . Until the 12th month of conventional treatment , the level of free T3 remained unchanged but decreased slightly during the extended-cycle regimen . In both groups there was a rise of sex hormone-binding globulin by 210 - 230 % after 3 months and by 220 - 250 % after 12 months . The levels of total testosterone were reduced by about 40 % and those of free testosterone by 55 - 65 % after 3 and 12 months . CONCLUSION The results suggest that , during conventional and extended-cycle treatment with EE/DNG , a steady state in the effects on thyroid hormones and and rogen parameters was reached within 3 months and that the changes in the various hormonal parameters did not substantially differ between conventional and extended-cycle regimen The pharmacokinetics and and rogenic activity of Estrostep , a new oral contraceptive providing low-dose estrogen in a graduated sequence with a constant dose of progestin , were characterized in an open-label , nonr and omized study in 17 normally cycling women treated for three cycles with Estrostep .  Women received 1 mg of norethindrone acetate daily combined with 20 microg of ethinyl estradiol daily for the first 5 days ( 1/20 ) , 30 microg of ethinyl estradiol daily for the next 7 days ( 1/30 ) , and 35 microg of ethinyl estradiol daily for 9 days ( 1/35 ) . No medication was given for 7 days in each cycle to allow for withdrawal bleeding . Serial blood sample s for the measurement of ethinyl estradiol and norethindrone concentrations were collected on days 5 , 12 , and 21 of the third treatment cycle for the 1/20 , 1/30 , and 1/35 dose , respectively . Sex hormone-binding globulin ( SHBG ) and free testosterone were measured at baseline , on day 1 of cycles 2 and 3 ( SHBG only ) , and on days 5 , 12 , and 21 of cycle 3 . Mean steady-state plasma ethinyl estradiol and norethindrone concentrations increased over cycle 3 . The increases in ethinyl estradiol concentrations were proportional to dose . The increases in norethindrone concentrations were related to ethinyl estradiol-dependent increases in SHBG concentrations , which were 218 % , 253 % , and 296 % of baseline values on days 5 , 12 , and 21 , respectively . Mean plasma free testosterone concentrations decreased 47 % , 60 % , and 64 % below baseline on days 5 , 12 , and 21 of cycle 3 , respectively . Graduated ethinyl estradiol doses combined with a constant norethindrone acetate dose progressively increase SHBG and decrease free testosterone , which overrides any theoretic concerns of and rogenic activity of norethindrone acetate . Although true and rogenic activity can be determined only by assessing endpoints such as acne , hirsutism , and lipids in large controlled trials , the observed changes in circulating SHBG and free testosterone concentrations indicate that Estrostep has little , if any , intrinsic and rogenic activity At Hospital Saint-Louis in Paris France physicians compared data on 34 women using a levonorgestrel triphasic oral contraceptive ( OC ) with data on 32 women using a norgestimate triphasic OC  to examine the triphasic OCs effects on blood lipids and and rogen levels . They also compared post-OC blood lipids and and rogen levels with baseline blood lipids and and rogen levels . 47 % of all subjects smoked . After 6 cycles neither triphasic OC caused a significant difference in low density lipoprotein ( LDL ) cholesterol levels or in triglyceride levels . High density lipoprotein ( HDL ) levels in women using the norgestimate OC were significantly higher than in those using the levonorgestrel OC ( p = .001 ) . Accordingly the OCs had a significant effect on the LDL/HDL ratio . Levels of HDL subfractions ( HDL-2 and HDL-3 ) were also significantly higher in the norgestimate OC group than in the levonorgestrel OC group ( p < .01 ) . Women using the norgestimate OC had a significant increase in apolipoproteins A-1 and 1 - 2 after 6 cycles ( 12.7 % and 15.8 % respectively ; p = .001 and .0001 respectively ) . Neither triphasic OC affected a greater increase in sex hormone binding globulin ( SHBG ) levels than did the levonorgestrel OC ( 163 % vs. 72 % ; p = .0005 ) . It reduced the free testosterone level by 40 % . The levonorgestrel OC reduced it by 30 % but neither change was significant . Neither OC had an effect on body weight or blood pressure . These findings showed a trend toward lower and rogenicity with the norgestimate OC . The norgestimate OC may be beneficial since it was linked with significant increases in all HDL subfractions and SHBG Objective To compare the effects on ovarian activity of two oral contraceptives containing nomegestrol acetate (NOMAC)/17β-oestradiol ( E2 ) or drospirenone (DRSP)/ethinylestradiol ( EE ) . Methods In this open-label , r and omised , six-cycle study , 32 subjects using NOMAC/E2 ( 2.5–1.5 mg ; 24/4-day regimen ) were compared to 16 subjects using DRSP/EE ( 3 mg–30 μg ; 21/7-day regimen ) . Measurements included serum oestradiol , progesterone , follicle stimulating hormone ( FSH ) and luteinising hormone ( LH ) , and ultrasonography of follicular diameter . Results No ovulations occurred during treatment . Progesterone was fully suppressed , with mean maximum values < 2 nmol/l in both groups over all cycles . For NOMAC/E2 , mean maximum follicular diameter decreased from 19.3 mm before treatment to between 6.9 and 8.2 mm during treatment , with no subject having a follicular diameter ≥15 mm . For DRSP/EE , a decrease from 19.6 to between 7.4 and 10.8 mm was observed , with two subjects ( 12.5 % ) having a maximum follicle diameter ≥15 mm . These findings were consistent with observed FSH reductions ; full suppression of LH surges was observed in both groups . Post-treatment return of ovulation in both groups occurred on average 21 days after the last active tablet intake . Conclusions NOMAC/E2 achieves consistent ovulation inhibition , with suppressive effects on the ovaries at least similar to those of DRSP/EE Dehydroepi and rosterone sulfate ( DHEAS ) , which is of almost exclusive adrenal origin , is important for the and rogen status in women and prepubertal children , and DHEAS assays are used in the investigation of hyper and rogenism . There are conflicting reports concerning a diurnal variation in serum DHEAS . Although of adrenocortical origin , serum DHEAS levels are decreased by oral contraceptives ( OCs ) . DHEAS is strongly bound to serum albumin and has a very low metabolic clearance rate . The present study was performed in order to investigate whether a diurnal variation in serum DHEAS exists and , if so , whether this diurnal variation and the decreased DHEAS levels following OC use are related to alterations in adrenocortical steroids or to changes in serum albumin . Serum concentrations of DHEAS , dehydroepi and rosterone ( DHEA ) , cortisol and albumin were determined in blood sample s taken every half hour over a 24-h period in 10 healthy women before and during use of combined OCs .  Significant and frequently synchronous diurnal variations in serum DHEAS and albumin were found before as well as during OC use . These variations were not synchronous with the diurnal variation in DHEA . OCs significantly decreased serum DHEAS and albumin levels . A multiple regression analysis showed changes in albumin to be the most decisive factor for the diurnal variation as and for OC-induced changes in DHEAS . Changes in serum DHEAS during the day and following OC use are related to alterations in its main binding protein , serum albumin , rather than to changes in adrenocortical steroid secretion CONTEXT Continuous oral contraception may better suppress the ovary and endometrium , lending itself to the treatment of other medical conditions . OBJECTIVE Our objective was to determine the effects of continuous vs. cyclical oral contraception . DESIGN This was a r and omized double-blind trial . SETTING This trial was performed at an academic medical center in Pennsylvania . PATIENTS A total of 62 healthy women with regular menses were included in the study . INTERVENTION Cyclical oral contraception ( 21-d active/7-d placebo given for six consecutive 28-d cycles ) vs. continuous ( 168-d active pill ) therapy using a monophasic pill ( 20 microg ethinyl estradiol and 1 mg norethindrone acetate ) was examined . MAIN OUTCOME MEASURES The primary outcome was vaginal bleeding , and secondary outcomes included hormonal , pelvic ultrasound , quality of life , and safety measures . RESULTS There was no statistically significant difference in the number of total bleeding days between groups , but moderate/heavy bleeding was significantly greater with the cyclical regimen [ mean 11.0 d ( sd 8.5 ) vs. continuous 5.2 d ( sd 6.8 ) ; P = 0.005 ] , with both groups decreasing over time . Endogenous serum and urinary estrogens measured over six cycles were significantly lower ( P = 0.02 and 0.04 , respectively ) in the continuous group than the cyclical group . Women in the continuous group also had a smaller ovarian volume and lead follicle size over the course of the trial by serial ultrasound examinations . The Moos Menstrual Distress Question naire showed that women on continuous therapy had less associated menstrual pain ( P = 0.01 ) and favorable improvements in behavior ( P = 0.04 ) during the premenstrual period . CONCLUSIONS Continuous oral contraception does not result in a reduction of bleeding days over a 168-d period of observation but provides greater suppression of the ovary and endometrium . These effects are associated with improved patient symptomatology
target: However , subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences : COCs containing second generation progestins and /or the lower estrogen doses ( 20–25 µg EE ) were found to have less impact on SHBG concentrations .
  The current literature review and meta- analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations .
  Due to the SHBG increase , free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T , but both affect SHBG .
background: BACKGROUND Combined oral contraceptives ( COCs ) reduce levels of and rogen , especially testosterone ( T ) , by inhibiting ovarian and adrenal and rogen synthesis and by increasing levels of sex hormone-binding globulin ( SHBG ) .
  Although this suppressive effect has been investigated by numerous studies over many years , to our knowledge no systematic review concerning this issue had been performed .