title: Hypothalamo-pituitary-adrenal axis and adrenal function before and after ovariectomy in premenopausal women. Androgen levels in adult females: changes with age, menopause, and oophorectomy. Early postoperative changes in testosterone, dehydroepiandrosterone sulfate, and sex hormone-binding globulin after hysterectomy with or without concomitant oophorectomy. The association of endogenous sex hormones, adiposity, and insulin resistance with incident diabetes in postmenopausal women. Relation of demographic factors, menstrual history, reproduction and medication use to sex hormone levels in postmenopausal women Transdermal testosterone treatment in women with impaired sexual function after oophorectomy. X-Autosome translocations: Cytogenetic characteristics and their consequences [Subjective complaints and hormonal reactions in the first 6 weeks after hysterectomy]. Postmenopausal bilateral oophorectomy is not associated with increased fracture risk in older women. Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure. Endogenous androgen levels and well-being: differences between premenopausal and postmenopausal women Age-specific reference ranges for serum testosterone and androstenedione concentrations in women measured by liquid chromatography-tandem mass spectrometry. Testosterone and visceral fat in midlife women: the Study of Women's Health Across the Nation (SWAN) fat patterning study. Effects of aging on adrenal function in the human: responsiveness and sensitivity of adrenal androgens and cortisol to adrenocorticotropin in premenopausal and postmenopausal women. Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women. Measurement of total serum testosterone levels using commercially available kits: high degree of between-kit variability. Determinants of serum total and free testosterone levels in women over the age of 65 years. Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy. The effect of oophorectomy and hormone replacement on neurohypophyseal hormone secretion in women Testosterone deficiency in young women with 46,XX spontaneous premature ovarian failure. A longitudinal study of the perimenopausal transition: altered profiles of steroid and pituitary hormones, SHBG and bone mineral density. Sex steroids and affect in the surgical menopause: a double-blind, cross-over study Extremes of endogenous testosterone are associated with increased risk of incident coronary events in older women. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Effects of testosterone and estrogen replacement on memory function
abstract: The hypothalamo-pituitary-adrenal ( HPA ) axis is modulated by sex hormones . Few data exist on the relation between acute estrogen deficit and HPA axis response to corticotropin-releasing hormone ( CRH ) . The effects of a sudden drop in estradiol levels on basal and CRH-stimulated levels of ACTH , cortisol , testosterone , and rostenedione and 17-hydroxyprogesterone ( 17-OHP ) were assessed in nine premenopausal women ( 44 - 48 years of age ) , before and after ovariectomy .  The CRH test was performed before and 8 days after ovariectomy . A significant reduction in ACTH and adrenal steroids but not in cortisol response to CRH was observed after ovariectomy . The ratio of deltamax and rostenedione/17-OHP after CRH stimulation was substantially the same before and after ovariectomy , whereas deltamax 17-OHP/cortisol was significantly lower in ovariectomized women showing increased 21- and 11beta-hydroxylase activity . The results show that the acute estrogen deficit induces changes in the HPA axis characterized by reduced stimulated secretion of ACTH and steroids but normal stimulated cortisol production CONTEXT Changes in and rogen levels across the adult female life span and the effects of natural menopause and oophorectomy have not been clearly established . OBJECTIVE The objective of this study was to document the effects of age on and rogen levels in healthy women and to explore the effects of natural and surgical menopause . DESIGN , SETTING , AND PARTICIPANTS A cross-sectional study was conducted of 1423 non-healthcare-seeking women , aged 18 - 75 yr , r and omly recruited from the community over 15 months . MAIN OUTCOME MEASURES Serum levels by age of total testosterone ( T ) , calculated free T , dehydroepi and rosterone sulfate , and and rostenedione in a reference group of women free of confounding factors . Women in the reference group had no usage of exogenous steroid therapy ; no history of tubal ligation , hysterectomy , or bilateral oophorectomy ; and no hyperprolactinemia or polycystic ovarian syndrome . The effects of natural and surgical menopause on sex steroid levels were also examined . RESULTS In the reference population ( n = 595 ) , total T , calculated free T , dehydroepi and rosterone sulfate , and and rostenedione declined steeply with age ( P < 0.001 ) , with the decline of each being greater in the earlier than the later decades . Examination of serum and rogen levels by year in women aged 45 - 54 yr showed no independent effect of menopausal status on and rogen levels . In women aged 55 yr or older , those who reported bilateral oophorectomy and were not on exogenous steroids had significantly lower total T and free T levels than women 55 yr or older in the reference group . CONCLUSIONS We report that serum and rogen levels decline steeply in the early reproductive years and do not vary because a consequence of natural menopause and that the postmenopausal ovary appears to be an ongoing site of testosterone production . These significant variations in and rogens with age must be taken into account when normal ranges are reported and in studies of the role of and rogens in women OBJECTIVE To investigate the cross-sectional associations of  hysterectomy and oophorectomy  status , chronological age , and body mass index with early postoperative plasma levels of total and free T , DHEAS , and sex hormone-binding globulin ( SHBG ) . DESIGN A cross-sectional study . SETTING University hospital . PATIENT(S ) Ninety-two women age 35 - 47 years who were scheduled for hysterectomy and /or oophorectomy , advocated for benign gynecological pathologies . INTERVENTION(S ) Ninety-two eligible premenopausal women underwent hysterectomy and /or oophorectomy  , with plasma T , DHEAS , and SHBG levels assayed before surgery and during the postoperative period . MAIN OUTCOME MEASURE(S ) Effects of time x operation and age x operation interactions between oophorectomized and nonoophorectomized groups and within-subject main effect of time on plasma and rogen levels . RESULT ( S ) Of 92 women , hysterectomy alone was performed in only 49 ( 53.3 % ) cases . Oophorectomy , either unilateral or bilateral , was performed in 35.8 % of cases . Age x within-group interactions exhibited an important difference ( P=.03 ) in total T levels . The time x between- and within-group interaction effects on plasma DHEAS levels of postoperative day 7 , compared with day 1 , were statistically significant ( P<.001 ) . The effect of time x group interaction was remarkable , in terms of SHBG levels during the postoperative period . Age x oophorectomy interaction exhibited a statistically significant change of decline in DHEAS levels on postoperative day 7 ( P=.05 ) . CONCLUSION ( S ) The present study demonstrated a time and operation effect decline in plasma DHEAS levels . In contrast , the time x operation interaction on SHBG levels exhibited an increase toward postoperative day 7 CONTEXT In postmenopausal women , endogenous bioavailable testosterone ( T ) and estradiol ( E2 ) have been positively associated , and SHBG has been negatively associated , with incident type 2 diabetes ( T2DM ) . Previous studies have not explored possible factors explaining these relationships . OBJECTIVE Our objective was to examine the association of endogenous sex hormones with incident T2DM  in postmenopausal women and possible explanatory factors . DESIGN , SETTING , AND PARTICIPANTS The Multi-Ethnic Study of Atherosclerosis ( MESA ) is a prospect i ve study that included 1612 postmenopausal women aged 45 - 84 yr , followed between the years 2000 - 2006 , who were not taking hormone replacement therapy , had no prevalent cardiovascular disease or diabetes , and had complete ascertainment of sex hormones . MAIN OUTCOME MEASURES T2DM was defined based on fasting glucose and /or treatment for diabetes . RESULTS There were 116 incident cases of diabetes during follow-up . Across higher quartiles of bioavailable T and E2 and lower quartiles of SHBG , we found significantly greater hazards of developing incident T2DM ( all P for trend < or=0.001 ) . After adjustment for body mass index and insulin resistance estimated by homeostasis model assessment of insulin resistance , bioavailable T was no longer associated with incident T2DM . The associations of E2 and SHBG with incident T2DM were partially explained by body mass index and insulin resistance but persisted in fully adjusted models ( both P for trend < 0.02 ) . Dehydroepi and rosterone had no relationship with incident T2DM . CONCLUSIONS Adiposity and insulin resistance explained most of the association of bioavailable T but only partially explained the associations of E2 and SHBG with incident T2DM among postmenopausal women In postmenopausal women , levels of estrogens , and rogens , and perhaps prolactin have been related to risk of breast and other hormonal cancers in women . However , the determinants of these hormone concentrations have not been firmly established . Associations among various demographic , menstrual , and reproductive factors , medication use and endogenous sex hormone concentrations ( estradiol , free estradiol , estrone , estrone sulfate , testosterone , free testosterone , sex hormone binding globulin , and rostenedione , dehydroepi and rosterone ( DHEA ) , DHEA sulfate ( DHEAS ) , dihydrotestosterone , and prolactin )  were evaluated in a cross-sectional analysis from a simple r and om sample of 274 postmenopausal women selected from the Women ’s Health Initiative Dietary Modification Trial . In multiple regression analyses on log-transformed hormones , the concentrations of DHEA , and DHEAS were negatively and statistically significantly associated with age ( both β = −0.03 , P < 0.001 , respectively ) . Estradiol , estrone , DHEA , and free testosterone concentrations were higher in African-American than in non-Hispanic White women , but after multivariate adjustment the associations were statistically significant only for free testosterone ( β = 0.38 , P = 0.01 ) . Women who had a history of bilateral oophorectomy had a mean 35 % lower testosterone concentration compared with women with at least one ovary remaining ( β = −0.43 , P = 0.002 ) , and lower free testosterone ( β = −0.42 , P = 0.04 ) after multivariate adjustment . Women who reported regular use of NSAIDs had higher DHEA concentrations ( β = 0.20 , P = 0.04 ) and lower prolactin concentrations ( β = −0.18 , P = 0.02 ) compared with non-users . These results suggest that while age , oophorectomy status , and NSAID use may be associated with selected sex hormone concentrations , few menstrual or reproductive factors affect endogenous sex hormones in the postmenopausal period BACKGROUND The ovaries provide approximately half the circulating testosterone in premenopausal women . After bilateral oophorectomy , many women report impaired sexual functioning despite estrogen replacement . We evaluated the effects of transdermal testosterone in women who had impaired sexual function after surgically induced menopause . METHODS Seventy-five women , 31 to 56 years old , who had undergone oophorectomy and hysterectomy received conjugated equine estrogens ( at least 0.625 mg per day orally ) and , in r and om order , placebo , 150 microg of testosterone , and 300 microg of testosterone per day transdermally for 12 weeks each . Outcome measures included scores on the Brief Index of Sexual Functioning for Women , the Psychological General Well-Being Index , and a sexual-function diary completed over the telephone . RESULTS The mean ( + /-SD ) serum free testosterone concentration increased from 1.2+/-0.8 pg per milliliter ( 4.2+/-2.8 pmol per liter ) during placebo treatment to 3.9+/-2.4 pg per milliliter ( 13.5+/-8.3 pmol per liter ) and 5.9+/-4.8 pg per milliliter ( 20.5+/-16.6 pmol per liter ) during treatment with 150 and 300 microg of testosterone per day , respectively ( normal range , 1.3 to 6.8 pg per milliliter [ 4.5 to 23.6 pmol per liter ] ) . Despite an appreciable placebo response , the higher testosterone dose result ed in further increases in scores for frequency of sexual activity and pleasure-orgasm in the Brief index of Sexual Functioning for Women ( P=0.03 for both comparisons with placebo ) . At the higher dose the percentages of women who had sexual fantasies , masturbated , or engaged in sexual intercourse at least once a week increased two to three times from base line . The positive-well-being , depressed-mood , and composite scores of the Psychological General Well-Being Index also improved at the higher dose ( P=0.04 , P=0.03 , and P=0.04 , respectively , for the comparison with placebo ) , but the scores on the telephone-based diary did not increase significantly . CONCLUSIONS In women who have undergone oophorectomy and hysterectomy , transdermal testosterone improves sexual function and psychological well-being Summary To define the principal characteristics of X-autosome  translocations  , the authors present a study of 105 cases , five of which are personal observations . The autosomal pairs 15 , 21 , and 22 are affected by t(X-Aut ) more often than would be expected . The distribution of breakpoints on the X chromosome does not differ significantly from the expected distribution . The analysis of different patterns of inactivation seems to confirm that the inactivation could occur at r and om , but would be followed by a cellular selection favoring the better genetic balance . An estimate of the incidence of t(X-Aut ) is proposed , based upon the conclusions that only one chromosome is susceptible to translocation in meiosis in both males and females and that all affected men will be sterile , as will be 50 % of women Hormone profiles ( estradiol , testosterone , FSH , LH ) and typical estradiol deficiency phenomena were investigated prospect ively in the first 6 weeks after hysterectomy ( n = 50 ) and after additional bilateral adnexectomy ( n = 17 ) . In the second group estradiol was replaced transdermally from the 2nd postoperative day ( estradiol patch , 0.05 mg daily ) . In the 1st group 34 % of patients showed a significant decrease in estradiol , 28 % of patients a significant decrease in testosterone on the 3rd postoperative day which was no longer demonstrable after 6 weeks . In the second group no decrease in hormone levels was found . So the estradiol patch can replace estradiol to a sufficient degree and in particular physiologically even after bilateral oophorectomy Subjective complaints improved in both groups . Psychosomatic influence also seems to be of importance UNLABELLED We studied whether oophorectomy performed after menopause is associated with an increased risk of hip or vertebral fractures in 6295 Study of Osteoporotic Fractures participants . There was no association between postmenopausal oophorectomy and the risk of hip or vertebral fractures . INTRODUCTION Bilateral oophorectomy after natural menopause has been associated with an increased risk of osteoporotic fractures , potentially because of a decline in serum estradiol and testosterone levels after the oophorectomy . We prospect ively tested this hypothesis in the Study of Osteoporotic Fractures ( SOF ) . MATERIAL S AND METHODS We studied 6295 white women 65 years of age participating in the SOF who were not taking estrogen therapy at baseline . Hip fracture analyses included 708 hip fractures ; vertebral fracture analyses included 267 incident vertebral fractures . Baseline serum estradiol and free testosterone values were available in a small subset of participants . RESULTS AND CONCLUSION There were no significant differences in age , weight , or BMD between the women who underwent postmenopausal oophorectomy ( n = 583 ) and those who did not ( n = 5712 ) . Free testosterone levels were significantly lower among women who had a postmenopausal oophorectomy . A history of postmenopausal oophorectomy was not associated with an increased risk of hip ( hazard ratio [ HR ] = 1.1 ; 95 % CI = 0.9 - 1.5 ) or vertebral fracture ( HR = 0.7 ; 95 % CI = 0.5 - 1.2 ) . The relationship between oophorectomy and hip fracture was not altered by adding serum estradiol level ( HR = 1.3 ; 95 % CI = 0.5 - 3.2 ) or serum free testosterone level ( HR = 1.7 ; 95 % CI = 0.8 - 3.7 ) to the model . In summary , postmenopausal oophorectomy was not associated with an increased risk of hip or vertebral fracture in this cohort . These results are in contrast to previous findings , suggesting that the relationship between postmenopausal oophorectomy and fractures is not fully eluci date d and that incidental oophorectomy after menopause should still be considered carefully in each potential patient OBJECTIVE To assess the association between serum adrenal cortex autoantibodies and histologically confirmed autoimmune lymphocytic oophoritis . DESIGN Controlled , prospect i ve . SETTING Tertiary research center . PATIENT(S ) Two hundred sixty-six women with 46,XX spontaneous premature ovarian failure . INTERVENTION(S ) Ovarian biopsy in 10 women . MAIN OUTCOME MEASURE(S ) Serum adrenal cortex autoantibodies assessed by indirect immunofluorescence and autoimmune oophoritis assessed by immunohistochemical lymphocyte markers .  RESULT ( S ) We obtained a histologic diagnosis of autoimmune oophoritis in four women who tested positive for adrenal cortex autoantibodies and excluded this diagnosis in ovarian biopsies from six women who tested negative for adrenal cortex autoantibodies ( 4/4 vs. 0/6 ) . Women with histologically confirmed autoimmune oophoritis had a greater total ovarian volume as assessed by transvaginal sonography ( 11.4 + /- 5.6 mL vs. 1.5 + /- 0.4 mL ) ( mean + /- SEM ) . They were also more likely to have sub clinical adrenal insufficiency and clinical signs of and rogen deficiency ( 3/4 vs. 0/6 ) . Overall , 10/266 women tested positive for adrenal cortex autoantibodies ( 3.8 % , 95 % confidence interval : 1.8%-6.5 % ) . CONCLUSION ( S ) In women who present with 46,XX spontaneous premature ovarian failure as their primary concern there is a clear association between serum adrenal cortex autoantibodies and the presence of histologically confirmed autoimmune oophoritis Objective : We investigated whether there is a relationship between and rogens levels and well-being in pre- and postmenopausal women . Design : We r and omly recruited 1423 women aged 18 to 75 years from the community via the electoral roll . Each provided a morning blood sample and completed the Psychological General Well Being Index question naire on the same day . Women were excluded if they took medication for any psychiatric illness , had abnormal thyroid function , or had documented polycystic ovarian syndrome . Analysis was by linear regression for well-being , including demographic and lifestyle variables as well as serum levels of and rogens . Results : We included 1224 women in the analysis . Being partnered was positively associated with well-being in premenopausal women . In postmenopausal women , well-being was positively related to age and exercising , whereas smoking , obesity , and postmenopausal hormone therapy use were each negatively associated with well-being . None of the measured and rogens ( total and free testosterone , dehydroepi and rosterone sulfate , and and rostenedione ) made an independent contribution to well-being in postmenopausal women ( n = 603 ) . However , for premenopausal women ( n = 621 ) , levels of dehydroepi and rosterone sulfate were independently and positively associated with the domain score for vitality . Conclusions : Our findings do not support an important independent role for and rogens as determinants of well-being in postmenopausal women . That dehydroepi and rosterone sulfate alone is associated with greater vitality in premenopausal women is of interest but requires further evaluation as an a priori hypothesis in another study 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 Visceral fat ( VF ) increases with the menopause and is an independent predictor of the metabolic syndrome , diabetes , and cardiovascular disease ( CVD ) in women . Little is known about how hormonal changes during the menopausal transition are related to the increase in VF . We aim ed to determine the relationship between bioavailable testosterone and VF in middle-aged women at various stages of the menopausal transition and whether this relationship is independent of age and other CVD risk factors . The Study of Women 's Health Across the Nation ( SWAN ) is a longitudinal , community-based study . This report uses baseline data from a population -based longitudinal ancillary study at the Chicago site to examine the cross-sectional relationship between testosterone and computed tomography (CT)-assessed VF  in women at different stages of the menopausal transition . Included are 359 women ( 47.2 % black ) , aged 42 - 60 years , who were r and omly selected from a complete community census in which a 72 % participation rate was achieved . In multivariate models , bioavailable testosterone was associated with VF independent of age , race , percent total body fat , and other cardiovascular risk factors . Bioavailable testosterone was a stronger predictor than estradiol and was interchangeable in its strength of association with sex hormone-binding globulin ( SHBG ) . As bioavailable testosterone was associated with VF even after adjusting for insulin resistance , this suggests that it plays an important role in regional fat distribution . Our findings may have direct implication s in explaining the effect of menopause-related testosterone predominance on VF accumulation and subsequent cardiovascular risk We sought to determine the effects of aging on several aspects of adrenal steroidogenesis in the hopes of characterizing the possible causes of adrenal and rogen deficiency in elderly women . To this end , we quantified basal morning concentrations of cortisol ( F ) , dehydroepi and rosterone ( DHEA ) , dehydroepi and rosterone sulfate ( DS ) , and and rostenedione ( A4 ) and then evaluated the effects of overnight dexamethasone ( DEX ) suppression followed by adrenal responses to grade d hourly infusions of ACTH , ranging from 20 - 1280 ng/1.5 m2 x h. Finally , we performed a st and ard 0.25-mg ACTH bolus stimulation test , with sampling at 1 h thereafter . Basal serum levels of DHEA , DS , and A4 were significantly reduced ( approximately 50 % each ) in a group of 35 healthy postmenopausal women , 55 - 68 yr old , compared to those in 30 healthy , regularly menstruating women , 20 - 25 yr old .  Post-DEX levels of these C19 steroids also were significantly lower in the older women than in the younger women ; the percent decrease after DEX for A4 was greater in the older women , whereas those in DHEA and DS were not age related . Basal and post-DEX levels of F were similar in both groups . Secretory responses of DS to ACTH were not informative due to its large plasma pool and slow clearance rate . The maximally stimulated levels of DHEA after ACTH bolus were significantly lower in the older women than in younger women ; those of A4 were similar in both age groups , and the maximally achieved levels of F were higher in the older women than in the younger women . The sensitivity of adrenal DHEA , A4 , and F to ACTH ( defined as the minimal dose of ACTH required to significantly increase the steroid levels above basal post-DEX values ) was similar in older and younger women . The responsiveness of the steroids of interest to ACTH ( defined as the slope of the dose-response curve over the linear portion of the dose-response curve ) also was similar among younger and older women . These data demonstrate that the deficiency in adrenal and rogen production in women is restricted to the delta5-pathway steroid products ( DHEA and DS ) , whereas there is no reduction in the capacity of the adrenal to produce A4 or cortisol . As DHEA and DS are likely to be produced mainly in the zona reticularis of the adrenal cortex , we propose that these data point to an alteration in that cortical zone as the cause of adrenal and rogen deficiency in aging . The reductions in A4 in aging are probably due to reduced ovarian secretion after menopause OBJECTIVE Excess weight has been associated with increased risk of cancer at several organ sites . In part , this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides . The objectives of the study were to examine the association of body mass index ( BMI ) with circulating and rogens ( testosterone , and rostenedione and dehydroepi and rosterone sulfate ( DHEAS ) ) , estrogens ( estrone and estradiol ) , sex hormone-binding globulin ( SHBG ) , IGF-I and IGF-binding protein (IGFBP)-3 , and the relationship between sex steroids , IGF-I and IGFBP-3 . DESIGN AND METHODS A cross-sectional analysis was performed using  hormonal and question naire data of 620 healthy women ( 177 pre- and 443 post-menopausal ) . The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk . RESULTS In the pre-menopausal group , BMI was not related to and rogens and IGF-I. In the post-menopausal group , estrogens , testosterone and and rostenedione increased with increasing BMI . The association with IGF-I was non-linear , with the highest mean concentrations observed in women with BMI between 24 and 25 . In both pre- and post-menopausal subjects , IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI . As for the correlations between peptide and steroid hormones , in the post-menopausal group , IGF-I was positively related to and rogens , inversely correlated with SHBG , and not correlated with estrogens . In the pre-menopausal group , similar but weaker correlations between IGF-I and and rogens were observed . CONCLUSIONS These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation , especially after menopause . Circulating IGF-I , and rogens and SHBG appear to be related to each other in post-menopausal women OBJECTIVE The measurement of total serum testosterone has an established clinical role in the management of male hypogonadism and female and rogen excess disorders . We studied the between-kit variability and precision of six different commercially available testosterone assays and compared them with an established in-house method . DESIGN Laboratory observational prospect i ve study . SETTING Tertiary university medical center clinical laboratory . PATIENT(S ) Three groups of sample s each of men ( n = 36 ) and women ( n = 15 ) who had high , normal , or low levels of sex hormone-binding globulin ( SHBG ) , respectively , were studied . INTERVENTION(S ) Individual and pooled ( male and female ) serum sample s were analyzed for total testosterone concentration using six different commercially available assays and one in-house method . MAIN OUTCOME MEASURE(S ) The between-kit variability and the effect of the mean ( + /- SD ) SHBG level were determined , the results obtained with the use of the kits and the in-house method were compared , and the intraassay variability ( i.e. , precision ) was evaluated . RESULT ( S ) Male sample s demonstrated a 26.3%-40.8 % variance in the results obtained with different kits , which was greatest for sample s with the lowest SHBG levels . For female sample s , between-kit variability ranged from 57%-115 % ( average , 77 % ) . The percent deviation of the results obtained with the use of commercial methods from those obtained with the use of our in-house assay was greater for men ( mean variance , 194 % ) than for women ( mean variance , 67 % ) . The female pool intraassay coefficient of variation was 3.8 % with the use of the in-house method and ranged from 8.9%-21.2 % with the use of the commercial kits . The male pool intraassay coefficient of variation was 3.1 % with the use of the in-house method and ranged from 3.3%-5.5 % with the use of the commercial kits . CONCLUSION ( S ) Most commercially available kits for measuring the total serum testosterone level demonstrated significant between-kit variability , which was greatest for female sample s. Further , sample s with the lowest SHBG levels had the highest between-kit variances . These data strongly suggest that the measurement of total serum testosterone using commercial kits may have limited utility , particularly for the detection of hyper and rogenemia CONTEXT Little is known about testosterone ( T ) levels and their determinants in women of late postmenopausal age . OBJECTIVE We describe levels of total and free T and selected factors that influence these levels in a r and om sample of older women . DESIGN Levels of serum total T and free T by microdialysis were measured using ultrasensitive assays in 347 community-dwelling women aged 65 - 98 yr enrolled in the Cardiovascular Health Study . Cross-sectional analyses were performed to define factors associated with total and free T levels . RESULTS In adjusted models : 1 ) total T levels declined with age until 80 , whereas free T levels did not vary by age ; 2 ) women with bilateral oophorectomy had 23 % lower total T and 16 % lower free T levels than those with at least one intact ovary ; 3 ) oral estrogen users had total and free T levels that were 47 % lower than never users ; 4 ) obese women had 47 % higher total T and 20 % higher free T levels , and overweight women had 24 % higher total T and 14 % higher free T levels , than normal weight women ; and 5 ) free T levels were 51 % higher in black women . Corticosteroid users had 75 % lower total T and 43 % lower free T levels than nonusers . CONCLUSIONS Bilateral oophorectomy , estrogen use , corticosteroid use , and low body mass index are independent risk factors for lower T levels in women aged 65 yr and over . Although highly prevalent in women of this age , the physiological significance of low T levels in late postmenopausal women requires further investigation Normal menopause is associated with vascular endothelial dysfunction , an early stage of atherosclerosis . The effect of premature ovarian failure ( or premature menopause ) on endothelial function in young women is unknown . Endothelial function was assessed in 18 women with premature ovarian failure before and after 6 months of hormone therapy  and was compared with the endothelial function of 20 age- and body mass index-matched premenopausal women .  Brachial artery diameter was measured both during hyperemia ( an index of endothelium-dependent vasodilation ) and in response to glyceryl trinitrate ( an index of endothelium-independent vaso-dilation ) . Flow-mediated dilation was significantly lower in women with premature ovarian failure at baseline ( increase in brachial artery diameter during hyperemia by 3.06 + /- 4.33 % ) than in control women ( increase by 8.84 + /- 2.15 % ; P < 0.0005 ) . Glyceryl trinitrate-induced vasodilation did not differ between the groups . After hormone therapy for 6 months , flow-mediated dilation was improved in women with premature ovarian failure , increasing by more than 2-fold ( 7.41 + /- 3.86 % ; P < 0.005 compared with pretreatment ) and reaching normal values ( P not significant compared with control women ) . Glyceryl trinitrate-induced vasodilation did not change after treatment in women with premature ovarian failure . Young women with premature ovarian failure have significant vascular endothelial dysfunction . Early onset of endothelial dysfunction associated with sex steroid deficiency may contribute to the increased risk of cardiovascular disease and mortality in young women with premature ovarian failure . Hormone therapy restores endothelial function within 6 months of treatment OBJECTIVE There is evidence to suggest that the release of neurohypophyseal hormones may be influenced by the circulating concentrations of gonadal steroids . We therefore monitored this relationship in women undergoing prophylactic bilateral oophorectomy at the time of hysterectomy with subsequent hormone replacement therapy  and compared it with that in women undergoing hysterectomy with conservation of OBJECTIVE To determine whether women with 46,XX spontaneous premature ovarian failure have lower serum free-T levels than do control women . DESIGN Cross-sectional . SETTING National Institutes of Health Clinical Research Center . PATIENT(S ) Women with 46,XX spontaneous premature ovarian failure ( n = 130 ) . INTERVENTION(S ) Evaluation while off any estrogen therapy and then again after receiving a st and ardized hormone regimen .  Regularly menstruating control women ( n = 65 ) were sample d during the midfollicular phase . MAIN OUTCOME MEASURE(S ) Serum total T by RIA  after extraction and column chromatography , free T by equilibrium dialysis , and sex hormone-binding globulin by immunoradiometric assay . RESULT ( S ) While off estrogen therapy patients had a median serum free-T concentration that was statistically significantly lower than controls ( 2.2 vs. 3.3 pg/mL ) . This dropped significantly lower to 1.9 pg/mL while the patients were on physiologic transdermal E(2 ) therapy . This is despite the fact that sex hormone-binding globulin levels did not change . While on E(2 ) therapy , 13 % of women ( 95 % confidence interval , 7.9%-20.3 % ) had serum free-T levels below the lower limit of normal ( < 1.1 pg/mL ) . CONCLUSION ( S ) As a group , young women with 46,XX spontaneous premature ovarian failure have reduced circulating free-T levels , both during an interval off of estrogen therapy and while on physiologic transdermal E(2 ) therapy From a longitudinal prospect i ve study , 160 women with spontaneous menopause and without steroid medication were followed during the transition from pre- to  postmenopause  . After 12 years 152 women were still participating in the study . Blood sample s were drawn every 6 months until 1 year after the menopause and every 12 months thereafter . Measurements of bone mineral density ( BMD ) on the forearm were performed every second year . All women routinely completed a question naire concerning symptoms frequently attributed to the climacteric period . All data were grouped around the onset of the menopause , thereby allowing longitudinal evaluation of the changes in the variables from the premenopausal to the postmenopausal period . The beginning of the perimenopausal period was characterized by transitory elevations of follicle-stimulating hormone ( FSH ) . A significant increase in serum levels of gonadotropins was observed for both FSH and luteinizing hormone ( LH ) from about 5 years before the menopause . Within the 6 month period around the menopause there was a further increase which culminated within the first postmenopausal year for LH and 2 - 3 years postmenopause for FSH . Thereafter , a continuous decrease in LH occurred over the following 8 years . With respect to FSH , there was a slight decline starting about 4 years postmenopause . During the premenopausal period an increasing frequency of inadequate luteal function or anovulation occurred and , in the postmenopausal years , the serum levels of progesterone ( P ) were invariably low . Gradually , the ratio between estrone ( E1 ) and 17-beta-estradiol ( E2 ) increased , reflecting the declining follicular steroidogenesis . A marked decrease in estrogen levels occurred during the 6 month period around the menopause , most pronounced in E2 . During the next 3 years , the levels of E2 and E1 showed an essentially parallel , moderate decline . Around the menopause , serum levels of testosterone ( T ) , delta 4- and rostenedione ( A ) and sex hormone-binding globulin ( SHBG ) showed small but significant decreases . From about 3 years postmenopause , the levels were relatively constant over the following 5 years . A decrease in BMD was observed in the postmenopause , and from about 3 years postmenopause , estradiol correlated positively with BMD . Before , as well as after the menopause , body mass index ( BMI ) showed an inverse correlation with SHBG . Postmenopausal and rostenedione correlated positively with E1 , E2 and T. BMI correlated positively with E1 and E2 . The concentrations of the free fraction of E2 and T are dependent on the levels of SHBG , which in turn has a negative correlation with BMI . The impact of this will influence the severity of symptoms , the degree of bone loss and the need for supplementary therapy The effect of estrogen and /or and rogen on mood in surgically menopausal women was investigated with a prospect i ve , double-blind , cross-over design . Oophorectomized women who received either estrogen ( E ) , and rogen ( A ) , or a combined estrogen- and rogen preparation ( E-A ) parenterally attained lower depression scores during both treatment phases compared to a placebo group ( PL ) , coincident with their higher plasma estrogen and testosterone levels . When steroids were withdrawn , depression scores of all oophorectomized women were significantly higher than those of a hysterectomized control group with intact ovaries ( CON ) . The A group also had higher hostility scores than the E , PL , and CON groups . These data provide evidence of a covariation between circulating levels of estrogen and testosterone and certain affects in healthy women CONTEXT Few studies have examined whether endogenous testosterone is associated with the development of  coronary heart disease ( CHD ) in women . OBJECTIVE This study tested the association of  total testosterone ( total T ) and bioavailable T ( BioT ) levels with risk of incident coronary events  among older community-dwelling women . DESIGN , SETTING , AND PARTICIPANTS This was a prospect i ve , population -based study of 639 postmenopausal women , aged 50 - 91 ( mean , 73.8 ) yr who had serum testosterone measurements at baseline ( 1984 - 87 ) and who were followed for incident CHD events through 2004 . MAIN OUTCOME MEASURES A total of 134 incident CHD events occurred during follow-up [ 45 nonfatal myocardial infa rct ions , 79 fatal myocardial infa rct ions , and 10 coronary revascularizations ] . RESULTS The median follow-up was 12.3 yr . Age-adjusted CHD risk estimates were similar for the four highest total T quintiles relative to the lowest , suggesting a low threshold . In age-adjusted analyses , the lowest total T quintile ( < /=80 pg/ml ) was associated with a 1.62-fold increased risk of incident CHD [ 95 % confidence interval ( CI ) , 1.10 - 2.39 ] compared to higher levels . BioT showed a U-shaped association with incident CHD . Age-adjusted risk for the lowest and highest BioT quintiles relative to the third were 1.79 ( 95 % CI , 1.03 - 3.16 ) and 1.96 ( 95 % CI , 1.13 - 3.41 ) , respectively . Additional adjustment for lifestyle , adiposity , estradiol , and ovarian status , or for CHD risk factor covariates , had minimal influence on results . CONCLUSIONS An optimal range of testosterone may exist for cardiovascular health in women , with increased risk of CHD events at low levels of testosterone overall and at high levels of the bioavailable fraction of testosterone OBJECTIVE To assess the efficacy and safety of a 300 mug/d testosterone patch for the treatment of hypoactive sexual desire disorder in surgically menopausal women on concomitant estrogen therapy . METHODS Five hundred thirty-three women with hypoactive sexual desire disorder who had undergone previous hysterectomy and bilateral oophorectomy were enrolled in a 24-week , multicenter , double-blind , placebo-controlled trial . Patients were r and omly assigned to receive placebo or the testosterone patch twice weekly . The primary efficacy endpoint was change from baseline at week 24 in the frequency of total satisfying sexual activity , measured by the Sexual Activity Log . Secondary measures included sexual desire using the Profile of Female Sexual Function and personal distress as measured by the Personal Distress Scale . Hormone levels , adverse events , and clinical laboratory measures were review ed . RESULTS Total satisfying sexual activity significantly improved in the testosterone patch group compared with placebo after 24 weeks ( mean change from baseline , 1.56 compared with 0.73 episodes per 4 weeks , P = .001 ) . Treatment with the testosterone patch also significantly improved sexual desire ( mean change , 10.57 compared with 4.29 , P < .001 ) and decreased personal distress ( P = .009 ) . Serum free , total , and bioavailable testosterone concentrations increased from baseline . Overall , adverse events were similar in both groups ( P > .05 ) . The incidence of and rogenic adverse events was higher in the testosterone group ; most and rogenic adverse events were mild . CONCLUSION In surgically menopausal women with hypoactive sexual desire disorder , a 300 mug/d testosterone patch significantly increased satisfying sexual activity and sexual desire , while decreasing personal distress , and was well tolerated through up to 24 weeks of use Objective : Testosterone insufficiency has been associated with psychosexual problems , reduced psychological well-being , and negative metabolic consequences , whereas less is known about the effects on cognition . The aim of this study was to investigate the effect of adding testosterone to estrogen therapy on memory functions in oophorectomized women . Methods : In a r and omized , double-blind , placebo-controlled design , women with surgically induced menopause ( n = 50 ; mean [ SD ] age , 54.0 [ 2.9 ] y ) received estradiol valerate in combination with testosterone undecanoate or placebo . The women were assessed with a self-report question naire regarding memory and neuropsychological tests for verbal and spatial episodic memory and incidental learning at baseline , at the time of crossover , and after completion of treatment . Results : Testosterone undecanoate 40 mg added to estrogen therapy had a negative effect on immediate but not delayed verbal memory at 24 weeks . Subjective and objective memory showed some correspondence as the women in the estrogen + placebo treatment group rated decreased everyday memory problems at 24 weeks compared with baseline . This was not observed in the women in the estrogen + testosterone treatment . Verbal attention span deteriorated from baseline with estrogen + placebo treatment but not with the estrogen + testosterone treatment . However , there was no significant treatment effect between the two groups . Conclusions : Adding testosterone to estrogen treatment deteriorated immediate verbal memory compared with estrogen + placebo , while other memory functions were unaffected
target: Subgroup analysis for assay type was statistically significant for spontaneous POI only .
  Sensitivity analyses of high- quality studies did not change the results , and result ed in a substantial decrease in heterogeneity in spontaneous POI studies .
  The current meta- analysis demonstrates that total testosterone concentrations are decreased in women with spontaneous POI or iatrogenic menopause .
background: BACKGROUND Increasing age and post-menopausal status are associated with decreasing and rogen concentrations in females .
  Women with premature loss of ovarian function , such as primary ovarian insufficiency ( POI ) or iatrogenic menopause may be at increased risk for diminished testosterone levels at a relatively young age .
  Differentiation between a hypo and rogenic or normo and rogenic state in women with premature loss of ovarian function is problematic due to trueness and precision problems using various testosterone assays .
  The current meta- analysis was conducted to evaluate current literature reporting serum total testosterone concentrations under these conditions , including stratification for various testosterone assays .