Effects of physiologic testosterone therapy on quality of life, self-esteem, and mood in women with primary ovarian insufficiency Androgen levels in adult females: changes with age, menopause, and oophorectomy. Testosterone patch for low sexual desire in surgically menopausal women: a randomized trial. Androgen enhances sexual motivation in females: a prospective, crossover study of sex steroid administration in the surgical menopause. Effects of metformin therapy on hyperandrogenism in women with polycystic ovarian syndrome [Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations]. Effects of transdermal testosterone application on the ovarian response to FSH in poor responders undergoing assisted reproduction technique--a prospective, randomized, double-blind study. Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women. Effect of exercise on serum androgens in postmenopausal women: a 12-month randomized clinical trial. Effect of high-dose isoflavones on cognition, quality of life, androgens, and lipoprotein in post-menopausal women [Ovarian suppression with Diane 35/50]. Androgen replacement therapy in Turner syndrome: a pilot study. Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause. Measurement of total serum testosterone levels using commercially available kits: high degree of between-kit variability. Is Reducing Ovarian Volume in Polycystic Ovarian Syndrome Patients after Administration of Metformin Associated with Improving Cardiovascular Risk Factors? Is aromatase cytochrome P450 involved in the pathogenesis of endometrioid endometrial cancer? Testosterone deficiency in young women with 46,XX spontaneous premature ovarian failure. Clinical, ultrasound and biochemical features of polycystic ovary syndrome in adolescents: implications for diagnosis. Elevated Serum Estradiol and Testosterone Concentrations Are Associated with a High Risk for Breast Cancer Ovarian hyperandrogynism as a result of congenital adrenal virilizing disorders: evidence for perinatal masculinization of neuroendocrine function in women. Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). Anti-Müllerian hormone is highly expressed and secreted from cumulus granulosa cells of stimulated preovulatory immature and atretic oocytes. Influence of body mass index on measured and calculated androgen parameters in adult women with Hirsutism and PCOS.
Objective Women with primary ovarian insufficiency ( POI ) display low and rogen levels , which could contribute to mood and behavioral symptoms observed in this condition . We examined the effects of physiologic testosterone therapy added to st and ard estrogen/progestin therapy on quality of life , self-esteem , and mood in women with POI . Methods One hundred twenty-eight women with 46,XX spontaneous POI participated in a 12-month r and omized , placebo-controlled , parallel- design investigation of the efficacy of testosterone augmentation of estrogen/progestin therapy .  Quality of life , self-esteem , and mood symptoms were evaluated with st and ardized rating scales and a structured clinical interview . Differences in outcome measures between the testosterone and placebo treatments were analyzed by Wilcoxon rank sum tests . Results No differences in baseline characteristics , including serum hormone levels ( P > 0.05 ) , were found . Baseline mean ( SD ) Center for Epidemiologic Studies Depression Scale scores were 10.7 ( 8.6 ) and 9.2 ( 7.8 ) for testosterone and placebo , respectively ( P = 0.35 ) . After 12 months of treatment , measures of quality of life , self-esteem , and mood symptoms did not differ between treatment groups . Serum testosterone levels achieved physiologic levels in the testosterone group and were significantly higher compared with placebo ( P < 0.001 ) . Baseline testosterone levels were not associated with either adverse or beneficial clinical effects . Conclusions A 150-&mgr;g testosterone patch achieves physiologic hormone levels in women with POI . Our findings suggest that augmentation of st and ard estrogen/progestin therapy with physiologic testosterone therapy in young women with POI neither aggravates nor improves baseline reports of quality of life or self-esteem and had minimal effects on mood . Other mechanisms might play a role in the altered mood accompanying this disorder 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 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 & NA ; Various parameters of sexual functioning were assessed in a prospect i ve , crossover investigation of 53 surgically menopausal women . Patients r and omly received either an estrogen‐ and rogen combined preparation , an estrogen‐alone drug , an and rogen‐alone drug , or a placebo .  Also included were a group of women who had undergone hysterectomy and whose ovaries had been left intact . Two treatment phases , each of 3 months ' duration , were separated by an intervening placebo month . Additionally , plasma levels of total estrogens and testosterone were assayed four times during the study concurrent with monitoring of sexual behaviors . It was clear that exogenous and rogen enhanced the intensity of sexual desire and arousal and the frequency of sexual fantasies in hysterectomized and oophorectomized women . However , there was no evidence that testosterone affected physiologic response or interpersonal aspects of sexual behavior . These findings suggest that the major impact of and rogen in women is on sexual motivation and not on sexual activity per se Polycystic ovarian syndrome ( PCOS ) is one of the most common endocrine diseases in women . This syndrome is characterized by hyper and rogenism , chronic anovulation , infertility and obesity . The association between PCOS-related hyper and rogenemia and insulin resistance is well documented in the literature . Insulin resistance and the result ing raised plasma levels of insulin are reported to be responsible for the high and rogen concentration observed in patients with PCOS . In this prospect i ve study , blood sample s for levels of testosterone ( T ) , dehydroepi and rosterone sulfate ( DHEAS ) , luteinizing hormone ( LH ) , follicle-stimulating hormone ( FSH ) , LH/FSH , prolactin and fasting blood sugar ( FBS ) before starting metformin administration were obtained r and omly from 40 women who were apparently obese , had PCOS and had been referred to a university hospital .  Metformin was then given at a dose of 500 mg three times a day for 8 weeks , after which time the pretreatment study was repeated . Clinical symptoms of PCOS , including acne and hirsutism score and body mass index ( BMI ) , were assessed before and after the treatment cycle . Metformin therapy result ed in a significant decrease in total testosterone levels and FBS . There was also a significant decline in BMI , length of the menstrual cycle , acne and hirsutism score . There were no significant changes in the levels of DHEAS , prolactin , FSH or LH , or in LH/FSH . The effect of metformin on subjects with elevated DHEAS levels was different to that on individuals with normal DHEAS levels . In the latter group there were only significant improvements in the length of the menstrual cycle , BMI and testosterone and DHEAS levels . It is concluded that metformin therapy in subjects with PCOS results in a decrease in fasting blood sugar and testosterone levels , and leads to a significant improvement in the clinical manifestation of hyper and rogenism . These responses also related to the level of adrenal function Anti and rogens or progestins with an anti and rogenic component usually have only a weak antigonadotropic activity . It is thus possible that the anti and rogenic effect on the cellular level is cancelled or at least reduced by an increased ovarian and rogen production . The aim of the four su bmi tted clinical studies of the progestin and anti and rogen dienogest alone ( 0.5 - 2 mg/day ) or of a combined regimen of ethinylestradiol ( 0.03 mg ) plus dienogest ( 2 mg ) ( EE/DNG ) was to examine the influence on the serum and rogen and SHBG concentrations as well as on the serum FSH , LH , progesterone and 17 beta-estradiol concentrations in young women . Like the progesterone derivatives , dienogest has a relatively low antigonadotropic activity . Inhibition of ovulation is mainly produced by peripheral mechanisms such as the reduction of preovulatory 17 beta-estradiol secretion .  Dienogest alone has no significant effects on the serum SHBG and and rogen concentrations . Unlike this , the combination of EE plus DNG markedly increases SHBG concentrations ( to 2.1 - 3.7 fold the basal levels ) . The decrease in serum and rogens with total testosterone ( by 17 and 40 % ) , free testosterone ( by 48 and 54 % ) and dehydroepi and rosterone sulfate ( by 51 % ) corresponds to the values shown in the literature for other oral contraceptives with modern progestins . EE/DNG does not affect the serum concentrations of 5 alpha-dihydrotestosterone ( DHT ) , although the marker of the peripheral transformation from T to DHT , and rostanediol glucuronide , is distinctly reduced ( by 38 % ) . In a double-blind comparison no differences are found between EE/DNG and a regimen combining 0.02 mg of ethinylestradiol and 0.150 mg of desogestrel . Solely the SHBG concentrations , with EE/DNG , as expected , are significantly higher . In a sequential regimen , dienogest , chlormadinone acetate and desogestrel ( progestins without binding to SHBG ) enhance the inhibitory effect of ethinylestradiol sulfonate on free testosterone , whereas norethindrone acetate and levonorgestrel ( progestins with a strong binding to SHBG ) reduce this effect of the estrogen significantly . These results exclude the possibility that the very distinct anti and rogenic effect of dienogest on a cellular level is neutralised or reduced by an increased systemic supply of and rogen BACKGROUND In primates , and rogens can play a synergistic role with FSH in promoting the early follicular recruitment , which is critical in assisted reproduction technique programmes . OBJECTIVE To assess whether poor responders can benefit from and rogen application . METHODS Inclusion criteria were a previous poor ovarian response to controlled ovarian stimulation and a decreased hormonal ovarian reserve . Selected women were r and omized to receive either transdermal application of testosterone ( n = 24 ) or placebo ( n = 25 ) gel for 15 days before FSH treatment for a second IVF cycle . Similar GnRH analogue and equivalent FSH daily doses were used in both cycles . The primary outcome was the total number of oocytes retrieved . RESULTS Testosterone gel application result ed in a significant increase in plasma testosterone levels but did not significantly improve the antral follicle count . Furthermore , after gel application , the main parameters of the ovarian response ( numbers of pre-ovulatory follicles , total and mature oocytes and embryos ) did not significantly differ between testosterone and placebo-treated patients . CONCLUSION No significant beneficial effects of and rogen administration on the ovarian response to FSH could be demonstrated . However , subsequent clinical trials are needed to determine whether an optimal dose and /or a longer duration of testosterone administration may be helpful 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 Postmenopausal women with elevated circulating and rogen concentrations have an increased risk of developing breast cancer , yet interventions to reduce and rogen levels have not been identified . We examined the effects of a 12-month moderate intensity exercise intervention on serum and rogens . The study was a r and omized clinical trial in 173 sedentary , overweight ( body mass index > or = 24.0 kg/m(2 ) , body fat > 33 % ) , postmenopausal women , ages 50 to 75 years , not using hormone therapy and living in the Seattle , WA area . The exercise intervention included facility-based and home-based exercise ( 45 minutes , 5 days per week of moderate intensity sports/recreational exercise ) . A total of 170 ( 98.3 % ) women completed the study , with exercisers averaging 171 minutes per week of exercise . Women in the exercise and control groups experienced similar , nonsignificant declines in most and rogens . Among women who lost > 2 % body fat , testosterone and free testosterone concentrations fell by 10.1 % and 12.2 % between baseline and 12 months in exercisers compared with a decrease of 1.6 % and 8.0 % in controls ( P = 0.02 and 0.03 compared with exercisers , respectively ) . Concentrations of testosterone and free testosterone among exercisers who lost between 0.5 % and 2 % body fat declined by 4.7 % and 10.4 % . In controls who lost this amount of body fat , concentrations of testosterone and free testosterone declined by only 2.8 % and 4.3 % ( P = 0.03 and 0.01 compared with exercisers , respectively ) . In summary , given similar levels of body fat loss , women r and omized to a 12-month exercise intervention had greater declines in testosterone and free testosterone compared with controls . The association between exercise and breast cancer risk may be partly explained by the effects of exercise on these hormones Context : Recent interventional studies indicate that post-menopausal hormone replacement therapy is associated with an increased risk of cardiovascular mortality and breast cancer .  Isoflavones , a class of plant estrogens , have structural similarities to estradiol . Hence , isoflavones may exert beneficial estrogenic health effects in postmenopausal women with fewer adverse effects . Objective : To evaluate the effect of high-dose isoflavones on self-reported quality of life ( QOL ) , cognition , lipoproteins and and rogen status in post-menopausal women . Design and subjects : Double-blind , r and omized , placebo-controlled , 12-week trial of 93 healthy , ambulatory , post-menopausal women ( mean age 56 yr ) . The study was conducted at a tertiary care center in the United States . Intervention : Participants were r and omly assigned to receive 20 g of soy protein containing 160 mg of total isoflavones vs taste-matched placebo ( 20 g whole milk protein ) . Both soy and the placebo were provided in the form of a powder to be mixed with beverages . Main outcome measures : QOL was judged by the Menopause-specific Quality of Life ( MENQOL ) question naire while cognitive function was assessed with st and ard instruments . Total , free , and bioavailable testosterone , gonadotropins , SHBG , and fasting lipids were measured . Results : Eighty-four women ( 90 % ) completed the study ( active=38 , placebo=46 ) . There was a significant improvement in all 4 QOL subscales ( vasomotor , psychosexual , physical , and sexual ) among the women taking isoflavones , while no changes were seen in the placebo group . No significant changes in cognition , serum and rogens or plasma lipids were seen within any of the groups . However , at the end of the study , a group-by-time interaction was observed such that total testosterone and HDL levels were significantly lower in the isoflavones compared to placebo groups . Conclusion : High-dose isoflavones is associated with improved QOL among women who have become menopausal recently . Hence , the timing of isoflavone supplementation with regards to the onset of menopause appears to be important . The use of isoflavones , as an alternative to estrogen therapy , may be potentially useful and seemingly safe in this group of women who are looking for relief from menopausal symptoms In this study , hormone profiles were studied using Diane 35 and Diane 50 before and after treatment for 4 - 25 months . A comparison of the hormone profiles with Diane 35 or Diane 50 should investigate , if both preparations induce complete ovarian suppression , independent of the given dose of ethinyl oestradiol .  43 patients were treated with Diane 35 and 15 women with Diane 50  over a different lengths of time -- up to a period of 25 cycles . Parallel to the determination of the hormone profiles ( luteinising hormone [ LH ] , follicle stimulating hormone [ FSH ] , prolactin , oestrone [ E1 ] , oestradiol [ E2 ] , progesterone , total testosterone [ T. T. ] , free testosterone [ F. T. ] , dehydroepi and rosterone-sulfate [ DHEA-S ] , delta-4- and rostenedione [ A. ] and sex hormone binding globulin [ SHBG ] ) , observations on the and rogen symptoms before treatment and their course during therapy were made . Moreover , the ratios of LH/FSH and E1/E2 as well as the and rogenic index , the ratio of total testosterone/SHBG were determined as control of treatment effects . The most important hormonal changes , which had been observed during a period up to two years are the following : --LH and FSH suppression -- prolactin with increasing tendency -- decrease of the total and rogens and free testosterone-- decrease of the oestrogens E1 , E2 - -increase of SHBG . The confirmation of the efficacy of the anti- and rogen/oestrogen combination was reflected by the decline of the and rogenic index in all groups . Acne and seborrhoe improved after 3 - 4 cycles ; alopecia after 8 - 9 cycles and hirsutism diminished after 3 cycles of treatment . In spite of different doses of the combined preparations with 2 mg cyproteronacetate and 0.035 or 0.050 mg ethinyloestradiol , no difference in ovarian suppression as well clinical effects could be found CONTEXT Women with Turner syndrome ( TS ) have reduced levels of and rogens due to ovarian failure . HYPOTHESES Morbidity associated with TS , such as bone fragility , metabolic changes , obesity , neurocognitive profile , and sexual problems may partly relate to and rogen insufficiency and improve on and rogen replacement therapy ( ART ) . OBJECTIVES The objective of the study was to determine the effect of and rogens on morbidity in TS . DESIGN Fourteen TS women ( aged 17 - 27 yr ) participated in a r and omized , double-blind , placebo-controlled crossover pilot . The study was conducted in a hospital outpatient clinic between December 2001 and July 2004 . INTERVENTION TS patients were on estrogen/progestin replacement therapy .  Subjects received oral 1.5 mg methyl testosterone ( ART ) or placebo for 1 yr and the alternative for another year . MAIN OUTCOME MEASURES The study compared body composition as a primary outcome , and physiology , biochemistry , visceral fat , cognition , and quality of life ( QOL ) as secondary outcomes . RESULTS ART as compared with placebo reduced total cholesterol , triglycerides , and high-density lipoprotein cholesterol . It improved bone mineral density , increased lean body mass , and decreased fat mass .  ART improved attention , reaction time , and verbal memory and had no effect on executive functions and spatial cognition . Patients reported improved QOL , including general health , coping with stress , and sexual desire . CONCLUSIONS And rogen insufficiency plays a role in TS-impaired body composition , neurocognition , and QOL , and these aspects improve with ART , which was safe and effective when given for 1 yr The investigation of estrogen and /or and rogen administration on physical and psychological symptoms in the surgical menopause was carried out in a prospect i ve , double-blind , crossover design . When patients who received either a combined estrogen- and rogen drug or and rogen alone  were compared with those who received estrogen alone or placebo , energy level , well-being , and appetite were increased ( p less than 0.01 ) . The and rogen-containing preparations also induced lower somatic , psychological , and total scores on the menopausal index . Superior functioning in the and rogen-treated groups occurred in association with higher plasma testosterone levels during the treatment phases ( p less than 0.01 ) . These data suggest that reduced levels of circulating testosterone subsequent to bilateral oophorectomy may play an important role in the development of physical and psychological symptoms that are frequent sequelae of this surgical procedure 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 Background Women with polycystic ovary syndrome ( PCOS ) are at increased risk for cardiovascular ( CV ) and metabolic disorders . There is a close relationship between elevated and rogen plasma levels and the ultrasound findings of stromal hypertrophy . In r and omized trials , the administration of metformin has been shown to be followed by an improvement in insulin sensitivity and decrease in and rogen levels in most women . In the present study , we investigate the association between reduced ovarian volume in PCOS patients after administration of metformin with improvement in CV risk factors . Material s and Methods This was a r and omized clinical trial study . A total of 28 women diagnosed with PCOS who referred to the infertility clinic were selected .  Anthropometric characteristics of the patients , mean ovarian volume and plasma levels of fasting blood sugar ( FBS ) , lipid profile , luteinizing hormone ( LH ) , follicle stimulating hormone ( FSH ) , estradiol , testosterone , 17-α-OH progesterone ( 17OHP ) , dehydroepi and rosterone sulfate ( DHEAS ) , C-reactive protein ( CRP ) and homocysteine ( Hcy ) were evaluated before and after treatment with 500 mg metformin , three times daily for three months . Statistics were calculated with the aid of SPSS 16.0 with student ’s paired t- and Pearson ’s correlation coefficient tests . Significance was set at p<0.05 . Results There were significant reductions in mean ovarian volume and body mass index ( BMI ) , in addition to CRP , Hcy , testosterone , FBS , HDL and LDL levels . There was a positive correlation between mean ovarian volume and waist-to-hip ratio (WHR).After treatment , there correlation noted with reduction in mean ovarian volume and decreased BMI , in addition to reductions in CRP , LDL , Hcy and testosterone levels . Conclusion A positive correlation may exist between reduced mean ovarian volume and improvement in CV risk factors  after administration of metformin ( Registeration Number : I RCT 138903244176N1 ) Prospect ively , the relationship between and rogen levels in the utero-ovarian circulation , aromatase activity in endometrial and body fat tissue , and the presence or absence of endometrioid endometrial cancer was studied in postmenopausal women . In 43 women with endometrioid endometrial cancer and 8 women with a benign gynecological condition , a hysterectomy with bilateral salpingo-oophorectomy was performed . Using tritium water-release assays , aromatase activities in endometrial and body fat tissue were determined and related to the steroid levels from the peripheral and the utero-ovarian venous circulation ( estradiol , and rostenedione , testosterone ) and to the presence or absence of endometrial cancer . Significant aromatase activity was found in both benign and malignant endometrial tissue sample s. Aromatase activity in sample s of endometrial tissue and in sample s of body fat did not correlate with steroid levels in peripheral or utero-ovarian venous blood . Aromatase activity in sample s of benign or malignant endometrium did not differ . Remarkably , in four women with mainly poorly differentiated endometrial cancer , very high aromatase activity was found in endometrial tissue . It is likely that multiple pathogenetic pathways exist that eventually lead to the formation of endometrioid endometrial cancer . The local availability of and rogens and the finding that aromatase activity is present in both endometrial cancer and benign endometrial tissue support the hypothesis that aromatase activity in the endometrium may play a role in malignant transformation by converting and rogens into mitogenic estrogens in the endometrial tissue 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 BACKGROUND Diagnosing polycystic ovary syndrome ( PCOS ) in adolescence is clinical ly challenging . The prevalence of clinical , ultrasound and biochemical features of PCOS in a community-based adolescent population using current diagnostic criteria has not previously been described . METHODS This was a prospect i ve cohort study with 244 unselected post-menarchal girls , mean age 15.2 years , of whom 91 % were Caucasian . Subjects were recruited from a large population -based birth cohort ( the Raine cohort ) .  Clinical hyper and rogenism ( HA ) was quantified using Ferriman-Gallwey scores . In the early follicular phase ( Day 2 - 6 ) , we measured circulating and rogens  and  sex hormone-binding globulin  by immunoassay , and ovarian morphology was assessed by transabdominal ultrasound examination .  BMI and waist-hip ratio were measured . RESULTS Normal ranges for early follicular phase and rogens in adolescence were derived for this population . The top 5 and 10 % of circulating free testosterone levels were 45.6 and 34.5 pmol/l , respectively . Fifty-one percent of girls reported menstrual irregularity . Clinical HA was uncommon , being observed in only 3.5 % of girls . Mean ovarian volume was greater than that reported by others in adult women and 35 % of girls had polycystic ovary morphology on transabdominal ultrasound . Taking the upper 5 % of free testosterone as HA , 42 girls ( 18.5 % ) would have met the Rotterdam criteria for PCOS , 11 girls ( 5 % ) the And rogen Excess Society criteria and 7 girls ( 3.1 % ) the National Institutes of Health criteria . CONCLUSIONS Menstrual irregularity is common in adolescence and does not relate to clinical or biochemical HA . Diagnostic criteria for PCOS which include ovarian volume and morphology may be of limited use in adolescence One in eight women in the United States will develop breast cancer , and deaths from breast cancer account for 17 % of all cancer deaths in women in the United States ( 1 , 2 ) . In 1997 , more than 180 000 new cases of breast cancer occurred in women in the United States ( 2 ) ; about half occurred in women 65 years of age or older . About 1 in 14 women aged 60 to 79 years will develop breast cancer compared with 1 in 26 women aged 40 to 59 years ( 2 ) . Endogenous estrogens may play an important role in the development of breast cancer ( 3 ) . Some ( 4 - 8 ) but not all ( 9 - 12 ) prospect i ve studies have found statistically significant positive associations between endogenous concentrations of estrogens and subsequent risk for breast cancer . Two recent review s concluded that increasing evidence supports a relation between estrogen concentrations and risk for breast cancer ( 3 , 13 ) . Women with higher bone mineral density , which is a cumulative measure of endogenous estrogen , have an increased risk for breast cancer ( 14 - 16 ) . Elevated endogenous serum concentrations of and rogens may also be related to an increased risk for breast cancer ( 5 , 7 , 17 ) , but this relation may not be independent of serum estrogens ( 8 , 18 , 19 ) . The best estrogen fraction with which to predict risk has not been identified ( 3 ) . Most studies have included measurements of total hormone levels ; the concentrations of free hormones may have even stronger associations . Most of the women in these studies were postmenopausal and younger than 65 years of age . Two r and omized trials ( 20 , 21 ) have shown a reduction in the occurrence of primary breast cancer in patients who have received tamoxifen and raloxifene .  In the Breast Cancer Prevention Trial ( 20 ) , 4 years of tamoxifen use led to a 45 % reduction in breast cancer incidence in 13 388 women . Women in this study were considered to be at high risk for breast cancer on the basis of the presence of certain risk factors , including age of 60 years or older ; about 30 % of women were 60 years of age or older . The Multiple Outcomes of  Raloxifene Evaluation ( MORE ) trial ( 21 ) found a 70 % reduction in risk for breast cancer , especially cases of estrogen receptor-positive cancer , after 33 months of treatment with raloxifene ( 21 ) . About 80 % of the 7704 women in this trial were older than 60 years of age . Because treatment with tamoxifen or raloxifene entails costs and risk ( 20 - 22 ) , it is important to identify women who are at greatest risk for breast cancer and are therefore most likely to benefit from antiestrogen therapies . Our study tests the hypothesis that serum concentrations of estradiol and testosterone , measured an average of 3 years before the clinical diagnosis of breast cancer , are related to risk for breast cancer in women 65 years of age or older . We hypothesized that measurements of serum hormones could be used to identify women at high risk for developing breast cancer . We used a case-cohort approach to compare serum hormone concentrations in 97 incident case- patients with breast cancer and 244 r and omly selected controls . Methods Study Sample All women were participants in the Study of Osteoporotic Fractures , a prospect i ve study of 9704 white , community-dwelling women who were at least 65 years of age and were recruited at four clinical centers across the United States ( 23 ) . Women were excluded from the study if they reported a bilateral hip replacement or the inability to walk without the assistance of another person . During 3.2 years of follow-up , we confirmed 121 cases of breast cancer , including 4 cases of carcinoma in situ , through review of medical records by a physician-epidemiologist ( 14 ) . We excluded women who reported current estrogen replacement therapy at baseline ; remaining were 97 confirmed cases of incident breast cancer . Using a case-cohort approach , we chose as controls a r and om sample of 247 women who survived to the first annual visit , denied a history of breast cancer , and did not report use of estrogen at baseline . Three of these women subsequently developed incident breast cancer and were included in the case-patient group . This study was approved by the biomedical institutional review board at each of the participating institutions . All participants provided informed consent . Sex-Steroid Hormones Serum specimens were obtained from all participants at a baseline examination in 1986 to 1988 . All participants were instructed to adhere to a fat-free diet during the night and morning before the examination to minimize lipemia that might interfere with assays . Blood was drawn between 8:00 a.m. and 2:00 p.m. , and serum was immediately frozen to 20 C. Within 2 weeks , all sample s were shipped to a central repository and stored in liquid nitrogen at 190 C until the assays were performed . We measured total estradiol , bioavailable estradiol or estradiol that was not bound by sex hormone-binding globulin ( SHBG ) , free estradiol , estrone , estrone sulfate , and rostenedione , dehydroepi and rosterone sulfate , total and free testosterone , and SHBG . All assays were done by Corning Nichols Institute ( San Juan Capistrano , California ) ; research ers were blinded to participants ' breast cancer status . The sensitivity of the assays refers to the lower limit of detection . Assays were performed concurrently on serum specimens from case- patients and controls . The intra-assay and total assay variability is expressed as a coefficient of variation . In this study , a range of coefficient of variation includes values for a low-concentration quality -control sample to those of a high-concentration quality -control sample . When no range is reported , the coefficient of variation was similar for both low- and high-concentration quality -control sample s. Total estradiol was measured by using liquid-liquid organic extraction , column chromatography , and radioimmunoassay ( coefficient of variation for intra-assay and total assay , 4 % to 12 % and 9 % to 11 % , respectively ; sensitivity , 7.3 pmol/L ) . Free estradiol was measured by using equilibrium dialysis and calculated by using the percentage of dialyzable estradiol and total estradiol ( coefficient of variation for intra-assay and total assay , 3 % to 4 % and 5 % , respectively ; sensitivity , 0.37 pmol/L ) . Percentage of non-SHBG-bound estradiol or bioavailable estradiol was measured by ammonium sulfate precipitation of SHBG-bound steroids ( coefficient of variation for intra-assay and total assay , 3 % and 6 % , respectively ) . The amount of estradiol that was non-SHBG-bound was then calculated as the product of the total amount of estradiol and the percentage of nonbound estradiol . Estrone was measured by using extraction , chromatography , and radioimmunoassay ( coefficient of variation for intra-assay and total assay , 6 % to 12 % and 8 % to 17 % , respectively ; sensitivity , 37 pmol/L ) . Estrone sulfate was measured by using organic extraction , enzymatic hydrolysis , celite chromatography , and radioimmunoassay ( coefficient of variation for intra-assay and total assay , 6 % to 7 % and 7 % to 8 % , respectively ; sensitivity , 143 pmol/L ) . And rostenedione was measured by using a radioimmunoassay after preparation for analysis by organic extraction and chromatography ( coefficient of variation for intra-assay and total assay , 6 % to 10 % and 7 % to 16 % , respectively ; sensitivity , 0.10 nmol/L ) . Dehydroepi and rosterone sulfate was measured by using radioimmunoassay after preparation for the analysis by serial dilution ( coefficient of variation for intra-assay and total assay , 6 % to 11 % and 9 % to 12 % , respectively ; sensitivity , 0.17 mol/L ) . Total testosterone was measured by using radioimmunoassay with chromatographic purification ( coefficient of variation for intra-assay and total assay , 6 % to 14 % and 5 % to 13 % , respectively ; sensitivity , 0.03 nmol/L ) . Free testosterone was measured by using equilibrium dialysis . Calculation of free testosterone was adjusted for albumin concentration ( coefficient of variation for intra-assay and total assay , 5 % and 5.4 % , respectively ; sensitivity , 34.7 pmol/L ) . Sex hormone-binding globulin was measured by using radioimmunoassay ( coefficient of variation for intra-assay and total assay , 7 % and 7.8 % , respectively ; sensitivity , 5.0 nmol/L ) . We formed the ratio of estrone sulfate to estrone to test the hypothesis suggested by Dorgan and coworkers ( 5 ) that women who develop breast cancer may be less able than other women to metabolize estrone to a less active form . We determined the reproducibility of selected hormone measurements in 20 postmenopausal women by assaying hormone levels in duplicate in different batches . Pearson correlations ( all significant at P<0.001 ) between the two measures were as follows : total testosterone , r=0.98 ; free testosterone , r=0.97 ; total estradiol , r=0.56 ; non-SHBG-bound estradiol , r=0.83 ; estrone , r=0.67 ; estrone sulfate , r=0.70 ; and rostenedione , r=0.77 ; dehydroepi and rosterone sulfate , r=0.97 ; and SHBG , r=0.97 . Initial and repeated mean values were similar . Variables Weight ( in lightweight clothing with shoes removed ) was recorded with a balance-beam scale . Self-reported height at 25 years of age was used to calculate the modified body mass index because women with low bone mass experience height loss secondary to vertebral fractures . A reproductive history , obtained by question naire and interview , included information on ages at menarche , menopause , and first birth ; parity ; and family history of breast cancer . Participants were asked about past use of estrogen replacement therapy , current and lifetime use of cigarettes and alcohol , and whether they walked for exercise .  We calculated the number of alcoholic drinks per week ; nondrinkers were coded as having zero intake . Statistical Analyses Characteristics of case- patients and controls were compared by t-test ( continuous variables ) or by chi-square test ( categorical variables ) . Sex-steroid hormone levels were not normally distributed . The nonparametric ( Wilcoxon two- sample ) test was used to compare the distribution of Women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency often have a polycystic ovary-like syndrome , consisting of hyper and rogynism , infertility , menstrual irregularities , and elevated LH levels . This is generally considered secondary to poor control of the congenital adrenal hyperplasia . However , our experience led us to suspect that ovarian hyper and rogenism occurs even when congenital adrenal hyperplasia is well controlled on glucocorticoid therapy . Therefore , we tested the hypothesis that congenital adrenal virilizing disorders result in ovarian hyper and rogenism . We studied eight women with congenital adrenal virilizing disorders , seven with well controlled classic 21-hydroxylase deficiency and one with congenital virilizing adrenal carcinoma removed at 1.7 yr of age . We also studied six women with late-onset 21-hydroxylase deficiency , without signs of congenital virilization . An ovarian source of and rogens was assessed after suppressing adrenal function with dexamethasone and then testing pituitary-ovarian function by a GnRH agonist ( nafarelin ) test . Five women with congenital adrenal virilizing disorders ( four with classic 21-hydroxylase deficiency and one with congenital virilizing adrenal carcinoma ) and one women with late-onset 21-hydroxylase deficiency had ovarian hyper and rogenism as determined by subnormal suppression of free testosterone after dexamethasone and /or by increased 17-hydroxyprogesterone response to nafarelin while on dexamethasone . All women with congenital adrenal virilization and ovarian hyper and rogenism had elevated LH levels after dexamethasone or elevated early LH response to nafarelin , which suggests that LH excess is the cause of their ovarian hyper and rogenism . This was not the case for the late-onset 21-hydroxylase-deficient woman . Our data are compatible with the hypothesis that congenital adrenal virilization programs the hypothalamic-pituitary axis for hypersecretion of LH at puberty . This is postulated to frequently cause ovarian hyper and rogenism even when adrenal and rogen excess is subsequently controlled by glucocorticoid therapy BACKGROUND Contrasting etiologic hypotheses about the role of endogenous sex steroids in breast cancer development among premenopausal women implicate ovarian and rogen excess and progesterone deficiency , estrogen excess , estrogen and progesterone excess , and both an excess or lack of adrenal and rogens ( dehydroepi and rosterone [ DHEA ] or its sulfate [ DHEAS ] ) as risk factors . We conducted a case-control study nested within the European Prospect i ve Investigation into Cancer and Nutrition cohort to examine associations among premenopausal serum concentrations of sex steroids and subsequent breast cancer risk . METHODS  Levels of DHEAS , ( Delta4- ) and rostenedione , testosterone , and sex hormone binding globulin ( SHBG )  were measured in single prediagnostic serum sample  s from 370 premenopausal women who subsequently developed breast cancer ( case patients ) and from 726 matched cancer-free control subjects .  Levels of progesterone , estrone , and estradiol  were also measured for the 285 case patients and 555 matched control subjects who had provided information about the day of menstrual cycle at blood donation . Conditional logistic regression models were used to estimate relative risks of breast cancer by quartiles of hormone concentrations . All statistical tests were two-sided . RESULTS Increased risks of breast cancer were associated with elevated serum concentrations of testosterone ( odds ratio [ OR ] for highest versus lowest quartile = 1.73 , 95 % confidence interval [ CI ] = 1.16 to 2.57 ; P(trend ) = .01 ) , and rostenedione ( OR for highest versus lowest quartile = 1.56 , 95 % CI = 1.05 to 2.32 ; P(trend ) = .01 ) , and DHEAS ( OR for highest versus lowest quartile = 1.48 , 95 % CI = 1.02 to 2.14 ; P(trend ) = .10 ) but not SHBG . Elevated serum progesterone concentrations were associated with a statistically significant reduction in breast cancer risk ( OR for highest versus lowest quartile = 0.61 , 95 % CI = 0.38 to 0.98 ; P(trend ) = .06 ) . The absolute risk of breast cancer for women younger than 40 followed up for 10 years was estimated at 2.6 % for those in the highest quartile of serum testosterone versus 1.5 % for those in the lowest quartile ; for the highest and lowest quartiles of progesterone , these estimates were 1.7 % and 2.6 % , respectively . Breast cancer risk was not statistically significantly associated with serum levels of the other hormones . CONCLUSIONS Our results support the hypothesis that elevated blood concentrations of and rogens are associated with an increased risk of breast cancer in premenopausal women This study investigated anti-Müllerian hormone ( AMH ) expression and secretion from cumulus granulosa cells ( GC ) and steroidogenesis in follicular fluids ( FF ) with relation to oocyte maturational stages and fertilization capacity in large preovulatory follicles . This prospect i ve study included 53 ovulatory women undergoing intracytoplasmic sperm injection .  FF and cumulus GC from 140 large preovulatory follicles were individually obtained during oocyte retrieval . Main outcome measures were oocyte maturation , fertilization and embryo quality . FF were assayed for AMH , progesterone , 17β-oestradiol and testosterone  . Cumulus GC were assayed for AMH mRNA expression . AMH mRNA expression and secretion in cumulus GC in preovulatory follicles containing germinal-vesicle ( GV ) and metaphase-I ( MI ) oocytes were significantly higher than follicles containing MII oocytes ( P<0.01 and P<0.0001 , respectively ) . In addition , FF AMH concentrations from atretic oocytes were significantly higher than from MII oocytes . No correlation was found between AMH expression and secretion to fertilization or embryo quality . FF of MI and GV oocytes had higher concentrations of testosterone and lower progesterone/oestradiol ratios than MII oocytes , and FF of atretic oocytes contained higher testosterone concentrations than FF of MII oocytes . AMH is highly expressed in and secreted from cumulus GC of preovulatory follicles containing premature and atretic oocytes . Anti-Müllerian hormone ( AMH ) is produced in the female exclusively by granulosa cells . AMH has recently been shown to be one of the most important markers of ovarian reserve and it is highly associated with ovarian follicular development . This study investigates AMH expression and secretion from cumulus granulosa cells ( GC ) and steroidogenesis in the follicular fluids ( FF ) with relation to oocyte maturational stages , and fertilization capacity in large preovulatory follicles . We conducted a prospect i ve study with 53 ovulatory women undergoing intracytoplasmic sperm injection . FF and cumulus GC from 140 large preovulatory follicles were individually obtained during oocyte retrieval . The main outcome measures were oocyte maturation , fertilization and embryo quality . FF were assayed for AMH , progesterone , 17β-oestradiol and testosterone . Cumulus GC were assayed for AMH mRNA expression . AMH mRNA expression in cumulus GC and AMH concentrations in FF of preovulatory follicles containing premature oocytes ( germinal vesicle ( GV ) and metaphase I ( MI ) ) were significantly higher than preovulatory follicles containing mature oocytes ( MII oocytes ) . In addition , FF AMH  concentrations of atretic oocytes were significantly higher than FF AMH of MII oocytes . No correlation was found between AMH expression and secretion for fertilization or embryo quality . FF of preovulatory MI and GV oocytes had higher levels of testosterone and lower progesterone/oestradiol ratios than MII oocytes , and FF of atretic oocytes contained higher testosterone levels than FF of MII oocytes . This study shows that  AMH  is highly expressed in and secreted from cumulus GC of preovulatory follicles containing premature and atretic oocytes There is growing evidence that obesity in women lead to a more severe form of hyper and rogenism and other endocrine abnormalities which may have some health implication s later in life . Obese females are at higher risk for metabolic syndrome due to severe hyper and rogenemia . Calculated values for free testosterone are equivalent to those obtained by equilibrium dialysis , which is one of the reference measurement procedures ( RMP ) for estimation of free testosterone and may be capable of replacing values estimated using RMP 's . For adult women correlations of body mass index ( BMI ) with calculated free ( cFT ) and bioavailable testosterone ( cBT ) are still rare , while these data are reported for peripubertal and adolescent girls . In this study we aim ed to investigate the association between BMI and different and rogen parameters ( including calculated free and bioavailable testosterone , free and rogen index , and sex hormone-binding globulin [ SHBG ] ) in adult women with Hirsutism and with PCOS . In hirsute women with BMI > or = 25 kg/m2 measured total testosterone ( TT ) was significantly higher , SHBG was significantly lower and the calculated and rogen parameter ( FAI , cFT and cBT ) were significantly higher compared to women with BMI < 25 kg/m2 . In PCOS women with BMI > or = 25 kg/m2 TT was significantly higher , SHBG was significantly lower and the calculated and rogen parameter ( FAI , cFT and cBT ) were also significantly higher compared to women with BMI < 25 kg/m2 . In both the Hirsutism and PCOS-group there was a positive correlation between BMI and TT , cFT , and cBT , while BMI was negatively correlated with SHBG . In summary , in adult women with Hirsutism and PCOS obesity is associated with increased levels of TT and decreased levels of SHBG result ing in significant elevated calculated free and bioavailable testosterone levels . Obesity might lead to a more severe form of hyper and rogenism with elevated calculated free and bioavailable testosterone in the study population
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 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 .