title: Nanostructured transdermal hormone replacement therapy for relieving menopausal symptoms: a confocal Raman spectroscopy study Use of complementary and alternative medicine during the menopause transition: longitudinal results from the Study of Women's Health Across the Nation A psycho-educational program for improving women's attitudes and coping with menopause symptoms. The effects of compounded bioidentical transdermal hormone therapy on hemostatic, inflammatory, immune factors; cardiovascular biomarkers; quality-of-life measures; and health outcomes in perimenopausal and postmenopausal women. The effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy in postmenopausal women: an observational cohort study. Intramuscular depot medroxyprogesterone versus oral megestrol for the control of postmenopausal hot flashes in breast cancer patients: a randomized study. Transdermal estradiol gel 0.1% for the treatment of vasomotor symptoms in postmenopausal women
abstract: OBJECTIVE : To determine the safety and efficacy of a transdermal nanostructured formulation of progesterone ( 10 % ) combined with estriol ( 0.1 % ) + estradiol ( 0.25 % ) for relieving postmenopausal symptoms . METHODS : A total of 66 postmenopausal Brazilian women with climacteric symptoms of natural menopause received transdermal nanostructured formulations of progesterone and estrogens in the forearm daily for 60 months to mimic the normal ovarian secretory pattern . Confocal Raman spectroscopy of hormones in skin layers was performed . Clinical parameters , serum concentrations of estradiol and follicle-stimulating hormone , blood pressure , BI-RADS classification from bilateral mammography , and symptomatic relief were compared between baseline and 60 months post-treatment . Clinical trials.gov : NCT02033512 . RESULTS : An improvement in climacteric symptoms was reported in 92.5 % of women evaluated before and after 60 months of treatment . The serum concentrations of estradiol and follicle-stimulating hormone changed significantly ( p<0.05 ) after treatment ; the values of serum follicle-stimulating hormone decreased after 60 months from 82.04±4.9 to 57.12±4.1 IU/mL. A bilateral mammography assessment of the breasts revealed normal results in all women . No adverse health-related events were attributed to this hormone replacement therapy protocol . CONCLUSION : The nanostructured formulation is safe and effective in re-establishing optimal serum levels of estradiol and follicle-stimulating hormone and relieving the symptoms of menopause . This transdermal hormone replacement therapy may alleviate climacteric symptoms in postmenopausal women Objective : This study examined whether use of complementary and alternative ( CAM ) therapies during the menopause transition varied by ethnicity . Design : The Study of Women 's Health Across the Nation is a prospect i ve cohort study following a group of 3,302 women from five racial/ethnic groups at seven clinical sites nationwide . Using longitudinal data encompassing 6 years of follow-up , we examined trends in use of five categories of CAM ( nutritional , physical , psychological , herbal , and folk ) by menopause status and ethnicity . To account for potential secular trends in CAM use or availability , we also evaluated the trends in CAM use over calendar time . Results : Approximately 80 % of all participants had used some form of CAM at some time during the 6-year study period . White and Japanese women had the highest rates of use ( 60 % ) , followed by Chinese ( 46 % ) , African American ( 40 % ) , and Hispanic ( 20 % ) women . Overall use of CAM therapy  remained relatively stable over the study period . In general ,  CAM  use did not seem to be strongly associated with change in menopause transition status . Use of CAM  among white women did not change with transition status . Among Chinese and African American participants , we observed an increase in  CAM use as women transitioned to perimenopause and a decrease in use of CAM  with transition to postmenopause . Among Hispanic and Japanese women , we observed a decrease in use of CAM  in early perimenopause , followed by an increase as women entered late perimenopause and a decrease as they progressed to postmenopause . Patterns of use for the five individual types of CAM varied . White women had relatively stable use of all  CAM therapies  through the transition . Japanese women decreased use of nutritional and psychological remedies and increased use of physical remedies as they transitioned into late perimenopause . Among African American women , use of psychological remedies increased as they progressed through menopause . Conclusions : Although CAM use did vary in some ethnic groups in relation to advancing menopause status , there was no evidence of influence of calendar time on CAM use . Patterns of CAM use during menopause are likely to be driven by personal experience , menopausal health , and access to therapies . Women 's personal preferences should be taken into consideration by healthcare providers for medical decision making during menopause and throughout the aging process OBJECTIVE To examine the impact of participation in a psycho-educational program on  women 's attitudes toward menopause , the perceived severity of their symptoms , and the association between the two . DESIGN Quasi-experimental . Data were gathered at baseline and 3 months after termination of the program . SETTING Two health maintenance organization clinics . PARTICIPANTS Eighty-two healthy 40- to 60-year-old women who chose to participate in the study . Thirty-six women participated in the program , and 46 women comprised the control group . INTERVENTION Program participants met for 10 weekly sessions to receive information from a professional team on subjects related to menopause and to share and discuss their experiences . MAIN OUTCOME MEASURES Attitudes toward menopause and severity of menopause symptoms . RESULTS The more negative the attitudes , the higher was the severity of symptoms . Participants reported significant improvements in attitudes and reductions in symptom severity compared to their own baseline scores and compared with the control group . CONCLUSIONS Participation in a program that combines delivery of information and processing of experiences on the cognitive , emotional , and social levels may improve women 's attitudes toward menopause and ease the perceived severity of their symptoms , thereby increasing quality of life Menopause impacts 25 million women world wide each year , and the World Health Organization estimates 1.2 billion women will be postmenopausal by 2030 . Menopause has been associated with symptoms of hot flashes , night sweats , dysphoric mood , sleep disturbance , and conditions of cardiovascular disease , depression , osteoporosis , osteoarthritis , depression , dementia , and frailty . Conventional hormone replacement therapy results in increased thrombotic events , and an increased risk of breast cancer and dementia as evidence d in large prospect i ve clinical trials including Heart and Estrogen/Progestin Replacement Study I and the Women 's Health Initiative . A possible mechanism for these adverse events is the unfavorable net effects of conjugated equine estrogens and medroxyprogesterone acetate on the hemostatic balance and inflammatory and immune factors . Physiologic sex steroid therapy with transdermal delivery for peri/postmenopausal women may offer a different risk/benefit profile , yet long-term studies of this treatment model are lacking . The objective of this study was to examine the long-term effects of compounded bioidentical transdermal sex steroid therapy including estriol , estradiol , progesterone , DHEA , and testosterone on cardiovascular biomarkers , hemostatic , inflammatory , immune signaling factors ; quality -of-life measures ; and health outcomes in peri/postmenopausal women within the context of a hormone restoration model of care . A prospect i ve , cohort , closed-label study received approval from the Human Subjects Committee . Recruitment from outpatient clinics at an academic medical center and the community at large result ed in three hundred women giving signed consent . Seventy-five women who met strict inclusion /exclusion criteria were enrolled .  Baseline hormone evaluation was performed along with baseline experimental measures . Following this , women received compounded transdermal bioidentical hormone therapy of BiEst ( 80%Estriol/20%Estradiol ) , and /or Progesterone for eight weeks to meet established physiologic reference ranges for the luteal phase in premenopausal women . The luteal phase hormone ratios were selected based on animal and epidemiologic studies demonstrating favorable outcomes related to traumatic , ischemic , or neuronal injury . Follow-up testing was performed at eight weeks and adjustment to hormone regimens were made including addition of and rogens of DHEA and Testosterone if indicated . Experimental subjects were monitored for 36 months . Baseline , 2-month , and annual values were obtained for : blood pressure , body mass index , fasting glucose , Homeostasis Metabolic Assessment of Insulin Resistance ( HOMA-IR ) , fasting triglycerides , total Factor VII , Factor VIII , fibrinogen , Antithrombin III , Plasminogen Activator Inhibitor1(PAL-1 ) , C-reactive protein ( CRP ) , Interleukin-6 ( IL-6 ) , Matrix Metalloproteinase-9 ( MMP-9 ) , Tumor Necrosis Factor-alpha ( TNF ) , Insulin-like Growth Factor ( IGF-1 ) , and sex steroid levels . Psychosocial measures included : Greene Climacteric Scale , Visual Analog Pain Scale , Hamilton Anxiety Scale , Hamilton Depression Scale , Holmes Rahe Stress Scale , Job Strain , and Home Strain . Health outcome measures included the number of prescribed medications used , number of co-morbidities , and endometrial thickness in postmenopausal women with intact uteri . Subjects receiving  compounded transdermal bioidentical hormone therapy showed significant favorable changes in : Greene Climacteric Scale scores , Hamilton Anxiety Scale , Hamilton Depression Scale , Visual Analog Pain Scale , fasting glucose , fasting triglycerides , MMP-9 , C-reactive Protein , fibrinogen , Factor VII , Factor VIII , Insulin-Like Growth Factor 1 , and health outcomes of co-morbidities and a number of prescribed medications . Antithrombin III levels were significantly decreased at 36 months . All other measures did not exhibit significant effects . Administration of compounded transdermal bioidentical hormone therapy in doses targeted to physiologic reference ranges administered in a daily dose significantly relieved menopausal symptoms in peri/postmenopausal women . Cardiovascular biomarkers , inflammatory factors , immune signaling factors , and health outcomes were favorably impacted , despite very high life stress , and home and work strain in study subjects . The therapy did not adversely alter the net prothrombotic potential , and there were no associated adverse events . This model of care warrants consideration as an effective and safe clinical therapy for peri/postmenopausal women especially in population s with high perceived stress and a history of stressful life events prior to , or during the menopausal transition Prior studies demonstrated improved menopausal symptom relief following treatment with compounded bioidentical hormone replacement therapy ; however , clinical effectiveness studies evaluating different routes of bioidentical hormone replacement therapy administration are lacking . The objective of this study was to determine the effectiveness of sublingual and topical compounded bioidentical hormone replacement therapy for the treatment of vasomotor , mood , and other quality -of-life symptoms in post-menopausal women . This was a prospect i ve , observational cohort study of women > or = 18 years of age who received a compounded sublingual or topical bioidentical hormone replacement therapy preparation between January 1 , 2003 and October 1 , 2010 in a community pharmacy . Data collection included patient demographics , comorbidities , hormone regimens , and therapeutic outcomes . Patients rated their vasomotor , mood , and quality -of-life symptoms as absent , mild , moderate , or severe at baseline , at one to three months follow-up , and three to six months follow-up . Baseline characteristics were compared using the chi-square test for categorical variables and the Wilcoxon rank sum test for continuous variables . Symptom intensity between baseline and follow-up periods were compared using the Wilcoxon signed-rank test . A total of 200 patients met study criteria ; 160 received topical bioidentical hormone replacement therapy  , and 40 received sublingual bioidentical hormone replacement therapy . Most sublingually-treated patients ( 70 % ) received an estrogen combination and 100 % received progesterone . Nearly half ( 43 % ) of the topically treated patients received an estrogen combination ( 43 % ) and 99 % received progesterone . The percentage of sublingually treated patients reporting " moderate " or " severe " symptoms was significantly reduced at one to three months follow-up for the following target symptoms : hot flashes ( 31 % , P = 0.04 ) , night sweats ( 38 % , P < 0.01 ) , irritability ( 36 % , P = 0.01 ) , anxiety ( 42 % , P < 0.01 ) , emotional lability ( 38 % , P < 0.01 ) , sleep disturbances ( 35 % , P < 0.01 ) , memory loss ( 35 % , P = 0.04 ) , fatigue ( 33 % , P = 0.04 ) , and libido ( 26 % , P = 0.03 ) . Similar reductions were seen at three to six months follow-up compared to baseline . Patients who received topical therapy did not experience significant symptom reductions at one to three months follow-up ; however , significant symptom reduction was seen at three to six months for the following : emotional lability ( 31 % , P < 0.01 ) , irritability ( 29 % , P = 0.02 ) , and night sweats ( 20 % , P = 0.04 ) . Compounded sublingual bioidentical hormone replacement therapy is effective in reducing vasomotor , mood , and quality -of-life symptoms experienced in post-menopausal women .  Topical therapy does not appear to improve symptoms as extensively or rapidly as sublingual therapy BACKGROUND Hot flashes are frequent in postmenopausal breast cancer patients , especially when treated with tamoxifen . Estrogen replacement therapy is the most effective treatment for hot flashes , but its use is controversial in breast cancer survivors . Progestins may offer a good alternative for the control of hot flashes in this setting ; in particular , oral megestrol acetate has been proven effective in a r and omized , placebo-controlled clinical trial . With the aim of further improving these results , we have design ed a r and omized study comparing oral megestrol acetate with depot intramuscular ( i.m . ) medroxyprogesterone acetate ( MPA ) for the control of hot flashes in postmenopausal patients with a history of breast cancer . PATIENTS AND METHODS Seventy-one postmenopausal patients were r and omized to receive an i.m . injection of depot MPA 500 mg on days 1 , 14 and 28 , or oral megestrol acetate 40 mg daily for 6 weeks . Patients recorded daily the number and severity of their hot flashes ; response was defined as a > or = 50 % decrease in the number and severity of hot flashes . RESULTS At week 6 , hot flashes were reduced by 86 % on average in the whole group of patients , without significant differences between the two progestins . Response was obtained by 75 and 67 % of patients receiving MPA or megestrol , respectively ( P = 0.5 ) . Responders were followed to assess maintenance of response ( without further treatment ) , which was significantly better with i.m . MPA : in this group , 89 % of responders still showed a benefit at week 24 , compared with 45 % in the megestrol group ( P = 0.03 ) . CONCLUSIONS Our study shows that a short cycle of i.m . depot MPA injections provides significant and long-lasting relief from postmenopausal hot flashes in patients with a history of breast cancer , offering an alternative to estrogen replacement therapy or prolonged administration of oral megestrol Objective : The objective of this study was to evaluate the efficacy and safety of three doses of estradiol gel 0.1 % ( Divigel , a novel formulation consisting of 1 mg estradiol per 1 g transdermal gel ) to reduce the frequency and severity of vasomotor symptoms and signs of vulvar and vaginal atrophy associated with menopause . Design : A total of 488 postmenopausal women were evaluated in a 12-week study comparing placebo with estradiol gel 0.1 % at doses of 1.0 , 0.5 , and 0.25 mg/day , with estimated daily deliveries of 0.027 , 0.009 , and 0.003 mg of estradiol , respectively . Primary endpoints were the change from baseline in daily frequency and severity of moderate to severe vasomotor symptoms . Change from baseline in the signs of vulvar and vaginal atrophy ( vaginal pH and percentage of superficial cells ) was also assessed . Results : Treatment with estradiol gel 0.1 % showed statistically significant reductions in frequency and severity of vasomotor symptoms from baseline compared with placebo as early as Week 2 that were maintained throughout treatment . Signs of vulvar and vaginal atrophy were also significantly improved from baseline with all three doses of estradiol gel 0.1 % compared with placebo . Conclusions : Low-dose transdermal estradiol gel 0.1 % is an effective treatment for relief of vasomotor symptoms , as well as signs of vulvar and vaginal atrophy , associated with menopause . Estradiol gel 0.1 % offers multiple dosing options to individualize patient therapy , including the lowest available effective dose ( 0.25 mg estradiol , delivering 0.003 mg/d estradiol ) to treat the vasomotor symptoms of menopause
target: The results showed that low-dose oral and transdermal estrogen in all dose ranges were more likely than placebo to decrease the frequency of VMS .
  Indeed , the nanostructured formulation was safe and effective in relieving the symptoms of menopause .
  Low-dose estrogen-based therapies can be the most effective regimens to relieve VMS .
  These medications can be used by different administration routes and formulations
background: BACKGROUND Menopause is a critical phenomenon in women 's life .
  After cardiac diseases , menopause is the second major cause of living with a disability in 45 - 60 year old women .
  The majority of women will experience bothersome  vasomotor symptoms ( VMS ) .
  Menopausal hormone therapy ( MHT ) is the most effective treatment for these symptoms .
  The objective of this review is to focus on hormone therapy for relieving postmenopausal vasomotor symptoms .