Androgens and estrogens in relation to hot flushes during the menopausal transition. Effect of intravaginal dehydroepiandrosterone (Prasterone) on libido and sexual dysfunction in postmenopausal women DHEA, important source of sex steroids in men and even more in women. A randomized trial of oral DHEA treatment for sexual function, well-being, and menopausal symptoms in postmenopausal women with low libido. Intravaginal dehydroepiandrosterone (Prasterone), a physiological and highly efficient treatment of vaginal atrophy Intravaginal dehydroepiandrosterone (prasterone), a highly efficient treatment of dyspareunia Supplementation with DHEA: effect on muscle size, strength, quality of life, and lipids. Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause Dehydroepiandrosterone for the treatment of hot flashes: a pilot study. Changes in hormones, lipids and symptoms after the administration of a commercial preparation with dehydroepiandrosterone in postmenopausal women. The effect of dehydroepiandrosterone on lumbar spine bone mineral density in patients with quiescent systemic lupus erythematosus. Low serum levels of sex steroids are associated with disease characteristics in primary Sjogren's syndrome; supplementation with dehydroepiandrosterone restores the concentrations. The endocrine transition around menopause ‐ a five years prospective study with profiles of gonadotropines, estrogens, androgens and SHBG among healthy women Serum steroid levels during 12-week intravaginal dehydroepiandrosterone administration 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. PERCEIVED EFFECTS OF TESTOSTERONE REPLACEMENT THERAPY IN PERIMENOPAUSAL AND POSTMENOPAUSAL WOMEN: AN INTERNET PILOT STUDY The use of dehydroepiandrosterone in the treatment of hypoactive sexual desire disorder: A report of gender differences Relation of demographic factors, menstrual history, reproduction and medication use to sex hormone levels in postmenopausal women Lack of influence of dyspareunia on the beneficial effect of intravaginal prasterone (dehydroepiandrosterone, DHEA) on sexual dysfunction in postmenopausal women. Endocrine, neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women. Effects of aging on adrenal function in the human: responsiveness and sensitivity of adrenal androgens and cortisol to adrenocorticotropin in premenopausal and postmenopausal women. A randomized controlled trial of dehydroepiandrosterone in postmenopausal women with fibromyalgia. Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive: II. Clinical effects.
In this paper , the association of hormones to vasomotor complaints during the menopausal transition is discussed . Fifty-seven regularly menstruating women without history of hormone replacement therapy ( HRT )  were selected for a longitudinal , prospect i ve study around the menopausal transition . The mean age at the start of the study was 51.3 ( + /-2.0 ) years . At intervals of 12 months all women went through a semi-structured interview and filled in question naires .  Venous blood sample s were collected every 12-month for analyses of estradiol ( E2 ) , testosterone , and rostendione , dehydroepi and rosterone-sulphate ( DHEA-S ) , follicle stimulating hormone ( FSH ) , thyrotropin ( TSH ) , and luteinizing hormone ( LH ) . Vasomotor complaints were tested using questions about hot flushes and bouts of sweating in terms of occurrence , frequency and degree of distress . Forty-six percent of the subjects reported hot flushes and bouts of sweating before menopause , increasing to 67 % during the first year after menopause and 49 % in the second year postmenopause . Low levels of estradiol and high levels of FSH were associated with vasomotor complaints before menopause . During menopause high levels of TSH were related to vasomotor complaints . The first year after menopause , women , who at this point achieved hot flushes , were characterised by high levels of E2 , but declining and low levels of FSH , but increasing . Postmenopausal , high levels of testosterone and DHEA-S seemed to protect against vasomotor symptoms . Our most important finding was , that among women who achieved hot flushes at the first assessment postmenopause , the high and rogen levels was a significant predictor of recovery from hot flushes at the last assessment , 1 year later Objective : The objective of this study was to provide evidence that the transformation of DHEA into both and rogens and /or estrogens locally in cells of the three layers of the vagina ( epithelium , lamina propria , and muscularis ) would have effects of greater impact , including effects on sexual function , than only effects on superficial epithelial cells as achieved with estrogens . Methods : This prospect i ve , r and omized , double-blind , and placebo-controlled phase III clinical trial has evaluated the effect of daily local intravaginal application of Prasterone ( dehydroepi and rosterone ; DHEA ) for 12 weeks on the domains of sexual dysfunction , namely , desire/interest , arousal , orgasm , and pain at sexual activity , in 216 postmenopausal women with moderate to severe symptoms of vaginal atrophy . Results : A time- and dose-dependent improvement of the four domains of sexual function was observed . At the 12-week time interval , the 1.0 % DHEA dose led , compared with placebo , to 49 % ( P = 0.0061 ) and 23 % ( P = 0.0257 ) improvements of the desire domains in the Menopause Specific Quality of Life and Abbreviated Sex Function question naires , respectively . Compared with placebo , the Abbreviated Sex Function arousal/sensation domain was improved by 68 % ( P = 0.006 ) , the arousal/lubrication domain by 39 % ( P = 0.0014 ) , orgasm by 75 % ( P = 0.047 ) , and dryness during intercourse by 57 % ( P = 0.0001 ) . Conclusions : By a local action in the vagina , DHEA applied daily at doses at which serum steroids remain well within normal postmenopausal values exerts relatively potent beneficial effects on all four aspects of sexual dysfunction . Such data indicate that combined and rogenic/estrogenic stimulation in the three layers of the vagina exerts important beneficial effects on sexual function in women without systemic action on the brain and other extravaginal tissues A major achievement from 500 million years of evolution is the establishment of a high secretion rate of dehydroepi and rosterone ( DHEA ) by the human adrenal gl and s coupled with the indroduction of menopause which stops secretion of estrogens by the ovary . Cessation of estrogen secretion at menopause eliminates the risks of endometrial hyperplasia and cancer which would result from non-opposed estrogen stimulation during the post-menopausal years . In fact , from the time of menopause , DHEA becomes the exclusive and tissue-specific source of sex steroids for all tissues except the uterus . Intracrinology , a term coined in 1988 , describes the local formation , action and inactivation of sex steroids from the inactive sex steroid precursor DHEA . Over the past 25 years most , if not all , the genes encoding the human steroidogenic and steroid-inactivating enzymes have been cloned and sequenced and their enzymatic activity characterized . The problem with DHEA , however , is that its secretion decreases from the age of 30 years and is already decreased , on average , by 60 % at time of menopause . In addition , there is a large variability in the circulating levels of DHEA with some post-menopausal women having barely detectable serum concentrations of the steroid while others have normal values . Since there is no feedback mechanism controlling DHEA secretion within ' normal ' values , women with low DHEA will remain with such a deficit of sex steroids for their remaining lifetime . Since there is no other significant source of sex steroids after menopause , one can reasonably believe that low DHEA is involved , in association with the aging process , in a series of medical problems classically associated with post-menopause , namely osteoporosis , muscle loss , vaginal atrophy , fat accumulation , hot flashes , skin atrophy , type 2 diabetes , memory loss , cognition loss and possibly Alzheimer 's disease . A recent r and omized , placebo-controlled study has shown that all the signs and symptoms of vaginal atrophy , a classical problem recognized to be due to the hormone deficiency of menopause , can be rapidly improved or corrected by local administration of DHEA without systemic exposure to estrogens . In addition , the four domains of sexual dysfucntion are improved . For the other problems of menopause , although similar large scale , r and omized and placebo-controlled studies usually remain to be performed , the available evidence already strongly suggests that they could be improved , corrected or even prevented by exogenous DHEA . In men , the contribution of adrenal DHEA to the total and rogen pool has been measured at 40 % in 65 - 75-year-old men . Such data stress the necessity of blocking both the testicular and adrenal sources of and rogens in order to achieve optimal benefits in prostate cancer therapy . On the other h and , the comparable decrease in serum DHEA levels observed in both sexes has less consequence in men who continue to receive a practically constant supply of testicular sex steroids during their whole life . In fact , in men , the appearance of hormone-deficiency symptoms common to women is observed at a later age and with a lower degree of severity . Consequently , DHEA replacement has shown much more easily measurable beneficial effects in women . Most importantly , despite the non-scientific and unfortunate availability of DHEA as a food supplement in the United States , a situation that discourages rigorous clinical trials on the crucial physiological and therapeutic role of DHEA , no serious adverse event related to DHEA has ever been reported in the world literature ( thous and s of subjects exposed ) or in the monitoring of adverse events by the FDA ( millions of subjects exposed ) , thus indicating , as expected from its known physiology , the excellent safety profile of DHEA . With today 's knowledge , one can reasonably suggest that DHEA offers the promise of a safe and efficient replacement therapy for the multiple problems related to hormone deficiency after menopause without the risks associated with estrogen-based or any other treatments INTRODUCTION Dehydroepi and rosterone ( DHEA ) and its sulfate DHEAS , which are the most abundant steroids in women , decline with age . We have shown association between low sexual function and low circulating DHEAS levels in women . AIM The aim of this study was to evaluate whether restoration of circulating DHEA levels in postmenopausal women to the levels seen in young individuals improves sexual function . METHODS Ninety-three postmenopausal women not using concurrent estrogen therapy were enrolled in a 52-week r and omized , double-blind , placebo controlled trial and received either DHEA 50 mg or placebo ( PL ) daily . MAIN OUTCOME MEASURES Efficacy was assessed through 26 weeks . The main outcome measures were the change in total satisfying sexual events ( SSE ) and the change in the Sabbatsberg Sexual Self-Rating Scale ( SSS ) total score . Secondary measures were the Psychological General Well-Being Question naire ( PGWB ) , and the Menopause-Specific Quality of Life Question naire ( MENQOL ) . Hormonal levels , adverse events ( AEs ) , serious adverse events ( SAEs ) and clinical labs were evaluated over 52 weeks . RESULTS Eighty-five participants ( 91 % ) were included in the 26-week efficacy analysis . There were no significant differences between the DHEA and PL groups in the change in total SSE per month or the SSS , PGWB , and MENQOL change scores . Overall AE reports and number of withdrawals as a result of AEs were similar in both groups ; however more women in the DHEA group experienced and rogenic effects of acne and increased hair growth . CONCLUSIONS In this study treatment of postmenopausal women with low sexual desire with 50 mg/day DHEA result ed in no significant improvements in sexual function over PL therapy over 26 weeks Objective : Because the secretion of dehydroepi and rosterone ( DHEA ) , the exclusive source of sex steroids in postmenopausal women , is already decreased by 60 % and continues to decline at the time of menopause , the objective of this study was to examine the effect of intravaginal DHEA on the symptoms and signs of vaginal atrophy . Methods : This prospect i ve , r and omized , double-blind and placebo-controlled phase III clinical trial studied the effect of Prasterone ( DHEA ) applied locally in the vagina on the signs and symptoms of  vaginal atrophy in 216 postmenopausal women . Results : All three doses ( 0.25 % , 0.5 % , and 1.0 % ) of DHEA ovules applied daily intravaginally induced a highly significant beneficial change in the percentage of vaginal parabasal and superficial cells and pH as well as in the most bothersome symptom at 2 weeks . At the st and ard 12-week time interval , 0.5 % DHEA caused a 45.9 ± 5.31 ( P < 0.0001 vs placebo ) decrease in the percentage of parabasal cells , a 6.8 ± 1.29 % ( P < 0.0001 ) increase in superficial cells , a 1.3 ± 0.13 unit ( P < 0.0001 ) decrease in vaginal pH , and a 1.5 ± 0.14 score unit ( P < 0.0001 ) decrease in the severity of the most bothersome symptom . Similar changes were seen on vaginal secretions , color , epithelial surface thickness , and epithelial integrity . Comparable effects were observed at the 0.25 % and 1.0 % DHEA doses . Conclusions : Local Prasterone , through local and rogen and estrogen formation , causes a rapid and efficient reversal of all the symptoms and signs of vaginal atrophy with no or minimal changes in serum steroids , which remain well within the normal postmenopausal range . This approach avoids the fear of systemic effects common to all presently available estrogen formulations and adds a novel physiological and rogenic component to therapy Objective To examine the effect of intravaginal dehydroepi and rosterone ( DHEA ) on pain at sexual activity ( dyspareunia ) identified as the most bothersome symptom of vaginal atrophy in postmenopausal women at both screening and day 1 . Methods This prospect i ve , r and omized , double-blind and placebo-controlled phase III clinical trial studied the effect of prasterone ( DHEA ) applied locally in the vagina on the severity of dyspareunia in 114 postmenopausal women who had identified dyspareunia as their most bothersome symptom of vaginal atrophy , while meeting the criteria for superficial cells ≤ 5 % and pH > 5.0 at both screening and day 1 . Results At the st and ard duration of 12 weeks of treatment , increasing doses of 0.25 % , 0.5 % and 1.0 % DHEA decreased the percentage of parabasal cells by 48.6 ± 6.78 % , 42.4 ± 7.36 % and 54.9 ± 6.60 % ( p < 0.0001 vs. placebo for all ) with no change with placebo ( p = 0.769 ) . The effects on superficial cells and pH were also highly significant compared to placebo at all DHEA doses . The severity score of pain at sexual activity decreased by 0.5 , 1.4 , 1.6 and 1.4 units in the placebo and 0.25 % , 0.5 % and 1.0 % DHEA groups , respectively , with the p value of differences from placebo ranging from 0.0017 to < 0.0001 . Conclusions Intravaginal DHEA , through local estrogen and and rogen formation , causes a rapid and highly efficient effect on pain at sexual activity without systemic exposure of the other tissues , thus avoiding the recently reported systemic effects of estrogens OBJECTIVE To evaluate the effects of combination estrogen/ and rogen therapy on muscle mass , strength and endurance , serum hormone and lipid profiles , and quality of life measures in postmenopausal women . METHODS Prospect i ve , r and omized , placebo-controlled pilot study at a tertiary care medical center . Fifty postmenopausal women were r and omized to a 12-week course of ( 1 ) dehydroepi and rostenedione ( DHEA ) 50 mg daily , ( 2 ) conjugated equine estrogen ( CEE ) 0.625 mg daily , ( 3 ) DHEA 50 mg+CEE 0.625 mg daily , or ( 4 ) placebo . Main outcome measures of lower extremity muscle ( calf ) mass , functional muscle parameters , serum hormone and lipid levels , and quality of life ( QOL ) were obtained at baseline and after treatment . Statistical analysis compared percent change from baseline values and treatment differences among outcomes . RESULTS Significant increases in mean DHEA , DHEA sulfate ( DHEA-S ) , testosterone , and and rostenedione levels were noted with DHEA alone or combined DHEA/CEE treatments when compared with placebo . Compared with no hormone therapy , none of the supplemental hormone groups caused significant changes in muscle mass , muscle strength , muscle endurance , feelings of well-being , sleep , or sexual function . CONCLUSIONS And rogen replacement therapy , with DHEA , to menopausal women increases serum and rogen levels without any appreciable effect on muscle cross-sectional area , muscle strength , muscle function , or improvement in health-related QOL Objective : The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepi and rosterone ( DHEA , Prasterone ) on moderate to severe dyspareunia or pain at sexual activity , the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause ( GSM ) . Methods : In a prospect i ve , r and omized , double-blind , and placebo-controlled phase III clinical trial , the effect of daily intravaginal 0.50 % DHEA ( 6.5 mg ) ( Prasterone , EndoCeutics ) was examined on four co primary objectives , namely percentage of parabasal cells , percentage or superficial cells , vaginal pH , and moderate to severe pain at sexual activity ( dyspareunia ) identified by the women as their most bothersome vulvovaginal atrophy symptom . The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups , respectively . Results : After daily intravaginal administration of 0.50 % DHEA for 12 weeks , when compared to baseline by the analysis of covariance test , the percentage of parabasal cells decreased by 27.7 % over placebo ( P < 0.0001 ) , whereas the percentage of superficial cells increased by 8.44 % over placebo ( P < 0.0001 ) , vaginal pH decreased by 0.66 pH unit over placebo ( P < 0.0001 ) , and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo ( P = 0.0002 ) . On the other h and , moderate to severe vaginal dryness present in 84.0 % of women improved at 12 weeks by 1.44 severity score unit compared to baseline , or 0.27 unit over placebo ( P = 0.004 ) . At gynecological evaluation , vaginal secretions , epithelial integrity , epithelial surface thickness , and color all improved by 86 % to 121 % over the placebo effect ( P < 0.0001 for all comparisons with placebo ) . Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology . The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at body temperature and this was reported in about 6 % of the participants . Conclusions : The daily intravaginal administration of 0.50 % ( 6.5 mg ) DHEA ( Prasterone ) has shown clinical ly and highly statistically significant effects on the four co primary parameters suggested by the US Food and Drug Administration . The strictly local action of Prasterone is in line with the absence of significant drug-related adverse events , thus showing the high benefit-to-risk ratio of this treatment based upon the novel underst and ing of the physiology of sex steroids in women BACKGROUND Published data regarding the negative risk-benefit ratio of traditional estrogen/progesterone hormone replacement therapy for menopausal symptoms have indicated the need for alternative treatments . Dietary supplements and herbal products are popularly used for menopausal control without a large evidence base . Therefore , a prospect i ve pilot trial using 50 mg of dehydroepi and rosterone ( DHEA ) once daily for 4 weeks following a baseline week was developed to explore whether DHEA has any efficacy in reducing hot flashes . Safety issues were also evaluated . PATIENTS AND METHODS Twenty-eight women were enrolled in this study , 22 of whom are evaluable . The primary outcome was the reduction in hot flash score ( frequency multiplied by average severity ) from baseline as measured by vali date d self-report daily hot flash diaries . RESULTS The mean hot flash score decreased 50 % from baseline , and there were no side effects that were significantly worse compared with baseline . Quality of life related to hot flashes showed statistically significant improvement after 4 weeks of DHEA therapy . CONCLUSION This pilot study provides data supporting the hypothesis that DHEA is well tolerated and can reduce hot flashes . Dehydroepi and rosterone should be studied further in a larger , placebo-controlled trial Dehydroepi and rosterone ( DHEA ) is an adrenal and rogen precursor of sex steroids with effects on a variety of physiological events [ 1 ] . DHEA and its sulfate ( DHEAS ) , as well as and rostendione , have minimal and rogenic activity [ 2 ] . It has been reported that serum levels of DHEA and DHEA-S substantially decrease with age , and experimental studies have demonstrated benefit with DHEA substitution at physiologic doses [ 3 ] . DHEA and DHEA-S are abundant in the circulation . DHEA-S accounts for more than 99 % of the steroid in the serum , with less than 1 % of free DHEA . Their main actions have been related to cellular control , immunoregulation , obesity and lipid metabolism [ 2 ] . Estrogen and and rogen replacement therapy date s to 1941 , when Geist and Salmon used and rogen therapy to treat climacteric symptoms [ 4 ] . DHEA has also been used as part of hormone therapy . In a study in which women from 60 to 70 years age received  DHEA  , a significant increase was observed in bone mineral density at the hip . This was followed by an increase in serum osteocalcin ( a bone formation marker ) , which was supposed to be due to DHEA and rogenic action . These results suggest that DHEA can be useful in the prevention and treatment of osteoporosis [ 5 ] . In another study , DHEA was given in a dose of 50 mg/day for 6 months to men and women aged 40 to 70 years . No changes were observed in estrone ( E ) and estradiol ( E2 ) serum levels in either sex . In women , there was a decrease in high-density lipoprotein cholesterol ( HDL-C ) levels without changes in the other lipids . Insulin sensitivity and mean body fat were not modified , and an increase in subjective physical well-being was cl aim ed in 67 % of men and in 84 % of women [ 6 ] . When DHEA was applied percutaneously in women from 60 to 70 years age for 12 months , no changes were observed in body weight . However , there was a 3.8 % decrease of body fat and an increase of 3.5 % in the muscular mass at the femoral level . HDL-C levels decreased 8 % , but the HDL-C/total cholesterol ratio did not change due to a parallel decrease of total cholesterol [ 7 ] . It then appears that the literature is controversial about DHEA effects . Commercial DHEA formulations are frequently used in Mexico , as in other countries . Therefore , the objective of this study was to evaluate a formulation of DHEA ( Siscelar plus  ) , commercially available in Mexico , on hormone and lipid levels and on climacteric symptoms after administration to postmenopausal women OBJECTIVE Because dehydroepi and rosterone ( DHEA ) is an adrenal steroid hormone with weak intrinsic and rogenic properties that can be converted in peripheral tissues into more potent sex hormones , one might expect a positive effect of DHEA on bone mineral density ( BMD ) . We evaluated the effects on lumbar BMD of oral DHEA , 200 mg/day , for 1 year in female patients with quiescent systemic lupus erythematosus ( SLE ) . METHODS The study subjects were 60 women with SLE . All participants gave informed consent to participate in a double-blind , placebo-controlled study on the effects of DHEA on fatigue and general well-being . BMD was measured with dual-energy x-ray absorptiometry ( DEXA ) at baseline and after 12 months . RESULTS Fifty-eight patients ( mean age 42.6 years ) could be evaluated ; 2 patients ( both in the DHEA group ) refused to undergo DEXA a second time . In premenopausal women , DHEA did not influence BMD significantly . There was a significant increase in BMD with use of DHEA in postmenopausal women who were not receiving bisphosphonates or estrogen-containing medications . This increase was not observed in the group receiving placebo . CONCLUSION In premenopausal women with quiescent SLE , use of DHEA does not have a significant effect on BMD .  DHEA may increase BMD in postmenopausal SLE patients if they are not already protected from bone loss by use of estrogens or bisphosphonates . Small numbers , due to the absence of stratification for menopausal status , and the use of antiresorptive agents at r and omization preclude firmer conclusions based on the results of this study CONTEXT Serum levels of the sex steroid prohormones dehydroepi and rosterone ( DHEA ) and DHEA sulfate ( DHEA-S ) decline upon aging and are reduced in primary Sjogren 's syndrome . OBJECTIVE Our aim was to investigate : 1 ) effects of 50 mg oral DHEA/day on changes in serum levels of DHEA and 12 of its metabolites ; 2 ) relationships between steroid levels and disease characteristics ; and 3 ) whether these parameters were influenced by DHEA . DESIGN Twenty-three postmenopausal women with primary Sjogren 's syndrome and subnormal levels of DHEA-S were included in a r and omized , 9-month , controlled , double blind crossover study . Liquid chromatography/mass spectrometry (MS)/MS and gas chromatography/MS were used to measure the sex steroids . Anti-SS-A/Ro and /or anti-SS-B/La , salivary gl and focus score , salivary flow rates , dry mouth and eye symptoms , and routine laboratory tests were assessed . RESULTS Baseline erythrocyte sedimentation rate was inversely correlated with testosterone ( Testo ) , dihydrotestosterone , and DHEA-S ( rs = -0.42 , -0.45 , and -0.58 , respectively ) . Dry mouth symptoms correlated with low Testo and and rostenedione , whereas dry eyes correlated with low estrogens , most strongly estrone ( rs = -0.63 ) . Presence of anti-SS-A and /or anti-SS-B was independently associated with low estradiol ( area under the receiver operating characteristic curve , 0.82 ) . All metabolites increased during DHEA but not during placebo . The relative increases were less for estrogens and Testo compared to dihydrotestosterone and glucuroni date d and rogen metabolites . Dry mouth symptoms decreased during DHEA therapy . CONCLUSIONS Disease manifestations in primary Sjogren 's syndrome were associated with low sex hormone levels , dry mouth symptoms with low and rogens , and dry eyes with low estrogens . Exogenous DHEA was preferentially transformed into and rogens rather than into estrogens OBJECTIVE The purpose of this study was to investigate the hormonal changes during the menopausal transition in a non- clinical population . METHODS Fifty-nine healthy Norwegian women participated in a five year prospect i ve longitudinal study during the transition from pre- to post-menopause , starting one to four years before menopause , and ending one to four years postmenopausal . None of these women were given hormone replacement therapy ( HRT ) . Blood sample s were collected every 12 months and luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) , steroid hormone binding globuline ( SHBG ) , prolactin ( PRL ) , estradiol ( E2 ) , estrone ( E1 ) , testosterone , and rostendione , dehydroepi and rostendione-sulphate ( DHEA-S ) , and thyroid stimulating hormone ( TSH ) were analyzed . RESULTS The serum levels of FSH and LH , E2 and E1 profile essentially confirmed previous data obtained in cross-sectional studies . A continuous increase in serum FSH and LH and a concomitant fall in E2 and E1 were observed in all women before menopause and in the two postmenopausal years . Both and rostendione and testosterone showed a decline three years before menopause . After the menopause , however , there were fluctuations in the testosterone levels . And rostendione correlated positively with both E2 and E1 and testosterone postmenopausally . Body mass index ( BMI ) did correlate with testosterone , but not with and rostendione . BMI correlated negatively with SHBG . No correlation was found between BMI and E2 , E1 , FSH and LH . CONCLUSION This longitudinal prospect i ve study of hormonal changes during the transition from pre- to postmenopause indicates that not only estrogen hormonal changes , but and rogen hormonal changes as well , precedes the menopause by several years Objective : Because a previous 1-week study has shown no or minimal changes in the serum levels of dehydroepi and rosterone ( DHEA ) and its metabolites after up to daily 1.8 % ( 23.4 mg ) intravaginal DHEA , the objective of the present study was to investigate the serum steroid levels during a 12-week daily intravaginal administration of 0 % , 0.25 % , 0.5 % , and 1.0 % DHEA ( Prasterone ) 1.3 mL ovules . Methods : In a double-blind , placebo-controlled phase III study , 218 postmenopausal women ( age range , 42 - 74 y ) were r and omized to receive daily one of four DHEA concentrations intravaginally .  Serum steroids were measured by a Good Laboratory Practice -vali date d mass spectrometry technology in sample s obtained at time of visit . Results : The serum levels of DHEA and 11 of its metabolites measured at screening , day 1 , and weeks 2 , 4 , 8 , and 12 in women showed no or minimal changes during the whole observation period , with all values remaining well within the limits of normal postmenopausal women . No accumulation of the steroid metabolites nor change in DHEA bioavailability was detected . Conclusions : The present data show that local daily intravaginal DHEA administration at DHEA doses of 3.25 - 13 mg was able to rapidly and efficiently achieve correction of all the signs and symptoms of vaginal atrophy and improve sexual function and caused no or minimal changes in serum sex steroid levels , which all remain within the normal postmenopausal range , thus avoiding the risks of all estrogen formulations 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 Women experience somatic , mood , energy , and libido changes during menopause .  Testosterone replacement therapy is being prescribed in conjunction with estrogen replacement therapy ( ERT ) for these symptoms . Little is known about women ’s perceptions of the benefits and risks of testosterone , so an Internet survey was conducted to elicit women ’s perceptions of the effects on mood , energy , sexuality , and somatic symptoms .  A sample of 61 women primarily from the United States and Canada participated in the survey ; one woman from Germany and one from Sweden also took part in the survey . Participants reported significantly improved sexuality and improved mood and vigor , with a decline in fatigue . Of the 7 somatic complaints assessed , improvements were noted in 5 ( sleep disturbances , hot flashes , night sweats , vaginal dryness , and appetite ) . A prospect i ve clinical trial is needed to confirm these results Data regarding the efficacy of dehydroepi and rosterone ( DHEA ) in the treatment of hypoactive sexual desire disorder ( HSDD ) are scarce and inconsistent . We aim ed to determine possible gender differences in the efficacy of DHEA as a treatment for HDSS . Postmenopausal women ( n=27 ) , and men ( n=21 ) with HSDD , were r and omized to receive either DHEA 100 mg daily or placebo for 6 weeks in a controlled , double blind study . Primary outcome measures were sexual function question naires . Hormone serum levels of DHEAS , total and bioavailable testosterone , estradiol , and urine levels of DHEA and and rosterone were also measured . Participants on active treatment showed a significant increase in circulating serum levels of DHEAS , while bioavailable testosterone levels increased in women only . In women only , significant interaction effects were observed for sexual arousal ( p<0.05 ) , satisfaction ( p<0.05 ) , and cognition ( trend ; p=0.06 ) . For arousal , a significant improvement was observed for the DHEA treated group at 6 weeks ( p=0.001 ) . Significant correlations were observed between bioavailable T and sexual cognitions , arousal and orgasm , while DHEAS was correlated with satisfaction . In the men , significant correlations were observed between testosterone and arousal ( r=.45 ) , sexual drive ( r=.50 ) and orgasm ( r=.55 ) . In women with HSDD , DHEA treatment had a significant beneficial effect on arousal , whereas no efficacy was demonstrated in men , indicating a possible gender difference . This improvement seems to be mediated via DHEA 's metabolism to testosterone . Our positive results suggest that the neurosteroid DHEA may be effective as a treatment for women with HSDD if administered at a dose of at least 100 mg per day 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 INTRODUCTION We have previously observed that intravaginal prasterone ( dehydroepi and rosterone , DHEA ) improved all domains of female sexual dysfunction ( FSD ) . AIM Investigate the influence of moderate/severe pain at sexual activity ( dyspareunia ) ( MSD ) at baseline on FSD following prasterone administration . METHODS The effect of daily administration of prasterone ( 0 , 3.25 mg , 6.5 mg or 13 mg ) for 12 weeks on FSD in 215 postmenopausal women with or without MSD at baseline was evaluated in a prospect i ve , r and omized , double-blind , and placebo-controlled phase III clinical trial . MAIN OUTCOME MEASURES Differences were examined on desire , arousal and orgasm . RESULTS Comparable benefits were observed in women not having MSD ( n = 56 ) vs. those having MSD ( n = 159 ) . The benefits over placebo in prasterone-treated women for desire , avoiding intimacy and vaginal dryness as well as for the total sexual domain of the MENQOL ( Menopause Specific Quality of Life ) question naire , ranged between 18.0 % and 38.2 % with P values of < 0.05 or < 0.01 except in one out of 12 subgroups . For the arousal/sensation , arousal/lubrication and summary score of the ASF ( Abbreviated Sexual Function ) question naire , in the MSD+ group , improvements of 64.2 % ( P = 0.01 ) , 118 % ( P = 0.001 ) and 31.1 % ( P = 0.03 ) were observed over placebo , respectively , while similar differences ( 58.0 % , 67.6 % and 32.1 % ) did not reach statistical significance in the MSD- group having up to only 44 prasterone-treated women compared with 119 in the MSD+ group . CONCLUSIONS No MSD at baseline does not apparently affect the effects of intravaginal prasterone on sexual dysfunction . Knowing the absence of significant effects of estrogens on FSD , the present data suggest that vulvovaginal atrophy ( VVA ) and vulvovaginal sexual dysfunction ( VVSD ) are two different consequences of sex steroid deficiency at menopause which can respond independently . In addition , the present data seriously question the justification of pain being part of FSD as well as the separation of FSD into separate domains Aging in women and men is characterized by a progressive decline of circulating dehydroepi and rosterone ( DHEA ) levels and its sulfate ester ( DHEAS ) . The improvement of wellbeing described in postmenopausal women treated with DHEA  suggests that this steroid may exert specific actions on the central nervous system ( CNS ) . The postmenopausal period is associated with several neuroendocrine modifications . The decrease of circulating levels of beta-endorphin is considered a hormonal marker of those changes . The aim of the present study was to investigate neuroendocrine and behavioral effects of three months of DHEAS supplementation in postmenopausal women . Postmenopausal women ( n = 22 ) were divided in three groups : the first group was treated with oral DHEAS ( n = 8) ( 50 mg/day ) , the second treated with the same dose of oral DHEAS + transdermal estradiol ( n = 8) ( DHEAS ) 50 mg/day , estradiol 50 micrograms/patch ) and the third with transdermal estradiol alone ( n = 6 ) ( 50 micrograms/day ) . Before and after 1 , 2 and 3 months of therapy , the following circulating steroid and protein hormone levels were evaluated : DHEA , DHEAS , and rostenedione , testosterone , estrone , estradiol , 17-hydroxyprogesterone , sex hormone-binding globulin ( SHBG ) , follicle-stimulating hormone ( FSH ) , luteinizing hormone ( LH ) , beta-endorphin , growth hormone ( GH ) and cortisol , and a Kupperman score was performed . Before and after treatments , plasma beta-endorphin levels were evaluated in response to three neuroendocrine tests : ( a ) clonidine , an alpha 2-presynaptic adrenergic agonist ( 1.25 mg i.v . ) ( b ) naloxone , an opioid receptor antagonist ( 4 mg i.v . ) and ( c ) fluoxetine , a serotonin selective reuptake inhibitor ( 30 mg p.o . ) . In both groups of women treated with  DHEAS  , mean basal serum DHEA , DHEAS , and rostenedione , and testosterone levels significantly increased after treatment , while no changes were shown in the group receiving estradiol alone . Serum estradiol , estrone , GH and plasma beta-endorphin levels significantly increased progressively for the three months of treatment , with higher levels for estrone and estradiol in subjects receiving estradiol alone or plus DHEAS . Serum SHBG , cortisol , and 17-hydroxyprogesterone did not show significant variations under any treatment . Serum LH and FSH levels showed a significant decrease in groups treated with estradiol alone or plus DHEAS at the second and third months . The Kupperman score showed that all treatments were associated with similar and progressive improvement . Before therapy clonidine , naloxone and fluoxetine stimuli failed to modify circulating beta-endorphin levels . After each of the treatments , the beta-endorphin response was completely restored and was similar , independent of the kind of therapy . Restoration of the beta-endorphin response to specific stimuli suggests that DHEAS and /or its active metabolites modulates the neuroendocrine control of pituitary beta-endorphin secretion , which may support the therapeutic efficacy of the DHEAS on behavioral symptoms 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 Patients with fibromyalgia ( FM ) consistently have adrenal hyporesponsiveness and low dehydroepi and rosterone ( DHEA ) levels . DHEA is promoted for and used by patients with FM . We tested the efficacy and safety of DHEA supplementation in ameliorating the symptoms of FM . METHODS In a double-blind crossover study , postmenopausal women with FM were r and omized to DHEA supplementation  ( 50 mg/day ) or placebo for 3 months , with a one-month washout period in between . Patients were assessed monthly for well-being and pain and by medical evaluations at the beginning and the end of each treatment period . The primary outcome was well being ; secondary outcomes were pain , fatigue , cognition , sexuality , functional impairment , depression , and anxiety . RESULTS A total of 52 patients were r and omized , 47 patients completed the  DHEA  treatment period , and 45 the placebo treatment period . After 3 months of treatment with 50 mg of DHEA , median DHEA sulfate blood levels had tripled , but there was no improvement in well-being , pain , fatigue , cognitive dysfunction , functional impairment , depression , or anxiety , nor in objective measurements made by physicians . And rogenic side effects ( greasy skin , acne , and increased growth of body hair ) were more common during the DHEA treatment period ( p = 0.02 ) . CONCLUSION DHEA does not improve quality of life , pain , fatigue , cognitive function , mood , or functional impairment in FM OBJECTIVES Combined oral contraceptives ( COCs ) decrease and rogen levels , including testosterone ( T ) , which may be associated with sexual dysfunction and mood complaints in some women . We have shown that ' co-administration ' of dehydroepi and rosterone ( DHEA ) to a drospirenone (DRSP)-containing COC restored total T levels to baseline and free T levels by 47 % . Here we describe the effects on sexual function , mood and quality of life of such an intervention . STUDY DESIGN This was a r and omized , double-blind , placebo-controlled study in 99 healthy COC starters . A COC containing 30 mcg ethinylestradiol ( EE ) and 3 mg DRSP was used for three cycles , followed by six cycles of the same COC combined with 50 mg/day DHEA or placebo . Subjects completed the Moos Menstrual Distress Question naire ( MDQ ) , the McCoy Female Sexuality Question naire and the short form of the Quality of Life Enjoyment and Satisfaction Question naire ( Q-LES-Q ) . Safety and tolerability , including effects on skin , were evaluated . RESULTS The addition of DHEA induced small but significant improvements compared to placebo in the MDQ score for autonomic reactions during the menstrual ( -2.0 vs. 0.71 ; p=0.05 ) and the premenstrual phase ( -3.1 vs. 2.9 ; p=0.01 ) and for behavior during the intermenstrual phase ( -1.4 vs. 3.6 ; p=0.02 ) . A significant difference was found in the MDQ score for arousal during the premenstrual phase in favor of placebo ( -5.0 vs. 1.0 ; p=0.01 ) . There were no statistically significant differences between groups for the MSFQ and Q-LES-Q scores .  DHEA ' co-administration ' result ed in an acceptable safety profile . DHEA negated the beneficial effect of the COC on acne according to the subjects ' self- assessment . CONCLUSIONS ' Co-administration ' with DHEA did not result in consistent improvements in sexual function , mood and quality of life indicators in women taking EE/DRSP . Retrospectively , the 50 mg dose of DHEA may be too low for this COC . IMPLICATION S A well-balanced judgment of the clinical consequences of normalizing and rogens during COC use may require complete normalization of free
There is no evidence that DHEA  improves quality of life but there is some evidence that it is associated with and rogenic side effects .
There is uncertainty whether DHEA decreases menopausal symptoms , but DHEA may slightly improve sexual function compared with placebo
BACKGROUND During menopause a decreasing ovarian follicular response generally causes a fluctuation and eventual decrease in estrogen levels .
This can lead to the development of various perimenopausal and postmenopausal symptoms ( for example hot flushes , night sweats , vaginal dryness ) .
Dehydroepi and rosterone ( DHEA ) is one of the main precursors of and rogens , which in turn are converted to testosterone and estrogens .
It is possible that the administration of DHEA may increase estrogen and testosterone levels in peri- and postmenopausal women to alleviate their symptoms and improve general wellbeing and sexual function ( for example libido , dyspareunia , satisfaction ) .
Treatment with DHEA is controversial as there is uncertainty about its effectiveness and safety .
This review should clearly outline the evidence for DHEA in the treatment of menopausal symptoms and evaluate its effectiveness and safety by combining the results of r and omised controlled trials .
OBJECTIVES To assess the effectiveness and safety of administering DHEA to women with menopausal symptoms in the peri- or postmenopausal phase .