Follicular phase hormone levels and menstrual bleeding status in the approach to menopause

OBJECTIVE: (1) Characterize the relationship between follicular phase hormone levels and menstrual bleeding patterns in the approach to menopause; (2) identify racial differences in hormone levels; (3) determine independent contributions of menstrual status, race, age, BMI, and smoking to hormone levels. DESIGN: Randomly identified, population-based cohort, stratified to obtain equal numbers of African American and Caucasian women, prospectively followed for 5 years. SETTING: Women in Philadelphia County, PA, identified by random-digit telephone dialing. PARTICIPANT(S): Women aged 35 to 47 years with regular menstrual cycles at enrollment (N = 436). DATA COLLECTION: Blood sampling twice in each of 7 assessment periods during days 1-6 of the cycle, menstrual dates identified through structured interview and daily symptom reports, anthropometric measures and standardized questionnaires at each assessment period. MAIN OUTCOME MEASURE(S): Serum levels of follicular E(2), FSH, inhibin B, and LH. RESULT(S): The mean levels of E(2), FSH, inhibin B, and LH were differentially associated with the 5 menstrual status groups defined by changes in bleeding patterns. Significant changes in hormone levels occurred prior to missed menstrual cycles for inhibin B, FSH, and LH. All hormones had a highly significant interaction between menstrual status and BMI. African American women had significantly lower levels of E(2) and LH compared to Caucasian women in univariate analyses. The interaction of race, menstrual status, and BMI was highly significant (P<.001) for E(2), with African American women having lower E(2) levels until postmenopause, when E(2) levels were higher in AA women with BMI > or =25 and BMI > or =30. CONCLUSION(S): Levels of E(2), FSH, LH, and inhibin B are significantly associated with menstrual bleeding patterns in late reproductive age women and differentiate the earliest stages of the menopausal transition. Racial differences in mean levels of E(2) appear strongly mediated by BMI.     

Urinary reproductive hormone level differences between African American and Caucasian women of reproductive age

OBJECTIVE: To compare urinary levels of reproductive hormones in African American and Caucasian women. DESIGN: Cross-sectional study. SETTING: Ten United States Air Force (USAF) bases. PATIENT(S): African American (n = 33) and Caucasian (n = 65) women of reproductive age from a larger study of USAF women (n = 170). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Urinary endocrine end points: follicular luteinizing hormone (LH), preovulatory LH, level of LH surge peak, early follicular follicle stimulating hormone (FSH), follicular LH:FSH ratio, midluteal FSH, FSH rise before menses, early follicular estrone 3-glucuronide (E(1)3G), midfollicular E(1)3G, periovulatory E(1)3G peak, midluteal E(1)3G, early follicular pregnanediol 3-glucuronide (Pd3G), follicular Pd3G, rate of periovulatory Pd3G increase, E(1)3G:Pd3G on the day of luteal transition, slope of E(1)3G:Pd3G, and midluteal Pd3G. RESULT(S): Relative to Caucasians, African American women had significantly lower follicular phase LH:FSH ratios (mean +/- SD: 0.7 +/- 0.4 vs. 1.0 +/- 0.6), lower follicular phase Pd3G levels (1.0 +/- 0.5 vs. 1.2 +/- 0.8 microg/mg creatinine), and lower rates of periovulatory Pd3G increase (0.5 +/- 0.7 vs. 1.0 +/- 1.2 microg/mg creatinine). CONCLUSION(S): Findings of this analysis should be considered preliminary evidence of racial differences in hormone levels. Future studies are needed to determine whether these differences have clinical significance.     

Effects of metformin therapy on hyperandrogenism in women with polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrine diseases in women. This syndrome is characterized by hyperandrogenism, chronic anovulation, infertility and obesity. The association between PCOS-related hyperandrogenemia and insulin resistance is well documented in the literature. Insulin resistance and the resulting raised plasma levels of insulin are reported to be responsible for the high androgen concentration observed in patients with PCOS. In this prospective study, blood samples for levels of testosterone (T), dehydroepiandrosterone sulfate (DHEAS), luteinizing hormone (LH), follicle-stimulating hormone (FSH), LH/FSH, prolactin and fasting blood sugar (FBS) before starting metformin administration were obtained randomly 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 resulted 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 hyperandrogenism. These responses also related to the level of adrenal function.     

Effects of ovarian drilling in middle Black Sea region Turkish women with polycystic ovary syndrome having normal and high body mass indices

AIM: To assess the effectiveness of laparoscopic ovarian drilling (LOD) in women with polycystic ovary syndrome (PCOS) with normal and high body mass indices (BMIs). METHODS: We investigated the effects of LOD process on two different groups of Turkish women with normal (n = 13) and high (n = 12) body mass indices. Three-puncture laparoscopy was performed under general anesthesia. Luteinizing hormone (LH), follicle-stimulating hormone (FSH), dehydroepiandrosterone-sulfate (DHEAS) and total testosterone (total T) levels were measured one menstrual cycle before the operation (in early follicular phase defined as day 3 of the menstrual cycle) and one menstrual cycle after the operation (in early follicular phase defined as day 3 of the menstrual cycle). RESULTS: Ovarian drilling had a positive effect on FSH increase and DHEAS, total testosterone and LH/FSH ratio decrease; but BMI levels had no effect on these hormonal changes, respectively (F = 0.343, P = 0564) (F = 0.790, P = 0383) (F = 0.083, P = 0776) and (F = 0.816, P = 0376). Ovarian drilling had a positive effect on LH decrease and BMIs were effective on this change (F = 6.946, P < 0.05). LH decrease in the group with normal BMI was significantly higher than the obese group with high BMI. Ten of 13 women with normal BMI (76.9%) and eight of 12 women with high BMI (66.6%) started to see regular menses 2 to 3 months after the procedure. CONCLUSION: Ovarian drilling is an effective procedure on PCOS. Women with lower BMI may benefit more from the procedure.     

Metformin therapy in women with polycystic ovary syndrome.

OBJECTIVE: To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters. METHOD: 50 Indian women with PCOS, 25 unmarried and 25 married, infertile women, were enrolled in this prospective clinical study. After a baseline workup, including body mass index (BMI), waist hip ratio (WHR), Ferriman Gallwey hirsutism scoring, menstrual pattern, levels of fasting insulin, lipids, oral glucose tolerance test (OGTT), serum gonadotropins, estradiol (E2), testosterone, androstenedione, sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulphate (DHEAS), patients were given 1000 gm of metformin for 6 months and then reevaluated. RESULT: In 41 of 50 women who completed treatment, significant improvement in BMI, WHR, menstrual cyclicity (80.5%), ovulation rate (66%), and pregnancy rate (28%) was noted. Statistically significant decrease in lutenising hormone (LH) and LH/FSH ratio with an increase in follicle stimulating hormone (FSH) levels were seen. Levels of high-density lipoprotein (HDL) cholesterol (Chol) increased along with a decrease in total cholesterol. Improvement was noted in ovarian volume, stromal thickness, and number of follicles. There was no change in hirsutism, acne, levels of other sex steroid hormones, and lipids. CONCLUSION: A 6-month course of metformin therapy may improve menstrual cyclicity and fertility in women with PCOS.     

Effect of short-term diet and exercise on hormone levels and menses in obese, infertile women

OBJECTIVE: To improve serum metabolic and endocrine measures known to influence fecundity. STUDY DESIGN: Twelve infertile, obese women were enrolled in a 12-week program of diet and exercise. Subjects underwent baseline testing for estrone (E1), estradiol (E2), testosterone (T), luteinizing hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), prolactin, fasting leptin, dehydroepiandrosterone sulfate (DHEAS), C-reactive protein (CRP) and total cholesterol. Glucose and insulin levels were measured fasting and 2 hours after a 75-g glucose load. Subjects attended three 1-hour exercise sessions per week and received instructions for a 1,200- to 1,300-kcal/day diet. Serum tests and body mass index (BMI) were remeasured after 12 weeks. Intermenstrual intervals were also recorded. At 24 weeks, subjects rated compliance with diet and exercise. Main outcome measures included change in serum variables, BMI and intermenstrual interval. RESULTS: BMI, total cholesterol and E1/E2 ratio significantly decreased over 12 weeks (mean difference +/- SEM, 2.06 +/- 0.51 kg/m2, 25.91 +/- 4.33 mg/dL and 0.7 +/- 0.22, respectively). No significant differences were noted for all other measures. Ten of the 12 subjects (83%) showed menstrual improvement, with 8 becoming eumenorrheic. CONCLUSION: Favorable metabolic and menstrual changes are possible in obese, infertile women after 12 weeks of diet and exercise.     

Breast cancer size in postmenopausal women is correlated with body mass index and androgen serum levels.

Our objective was to investigate the effects of age, weight, body mass index (BMI), sex steroid receptor status and serum parameters such as estradiol, testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and leptin on the size of a malignant breast tumor. A total of 62 premenopausal (median age 44.0 years) and 151 postmenopausal (median age 59.1 years) Caucasian women undergoing lumpectomy or mastectomy for invasive breast cancer were examined. Patient parameters (age, body weight, BMI), tumor parameters (tumor size, estrogen and progesterone receptor status) and serum parameters (estradiol, testosterone, androstenedione, DHEAS and leptin) were measured. An increase of BMI and DHEAS levels was associated with larger tumors by partial correlation (rp) analysis (rp = 0.418, p = 0.008; and rp = 0.329, p = 0.041, respectively), whereas higher androstenedione levels corresponded with smaller tumors. Furthermore, BMI, androstenedione and DHEAS levels were correlated: an increase in DHEAS was associated with higher androstenedione serum concentrations (rp = 0.603, p < 0.001), but was also associated with a lower BMI (rp = -0.378, p < 0.001). BMI and androstenedione serum concentrations were also associated (rp = 0.242, p = 0.009), thus closing a circle of mutual interactions. We conclude that, although breast cancer progression is characterized by autonomous growth that has become independent of growth regulatory mechanisms, tumor size at the time of detection is influenced by a complex system of counter-regulatory feedback mechanisms that might represent the body's physiological attempt to control the size of a malignant tumor.     

Serum leptin concentrations in pre- and postmenopausal women on sex hormone therapy.

AIM: The aim of the present study was to investigate the influence of endogenous estradiol and estrogen and estrogen-progestin therapies on concentration in pre- and postmenopausal women. MATERIALS AND METHODS: The study groups consisted of 26 women with surgical menopause (mean+/-standard deviation (SD): age 51.8+/-2.6 years, body mass index (BMI) 26.45+/-4.56 kg/m(2)), 54 with natural menopause (mean+/-SD: age 50.5+/-3.0 years, BMI 25.75+/-4.09 kg/m(2)) and 40 premenopausal controls (mean+/-SD: age 48.3+/-2.3 years, BMI 26.23+/-4.12 kg/m(2)). The group with surgical menopause received estradiol transdermally (50 microg/day) and those with natural menopause received additionally medroxyprogesterone acetate (5 mg/day) for the last 12 days of the cycle. Before and after 4 months of therapy, body weight, waist and hip circumferences and blood pressure were measured, and BMI and waist-to-hip ratio (WHR) were calculated. Serum leptin, follicle-stimulating hormone (FSH), estradiol (E(2)), testosterone, prolactin and dehydroepiandrosterone sulfate (DHEAS) were measured prior to and after treatment. RESULTS: Leptin concentrations did not differ statistically among the groups. No correlations between leptin and E(2), FSH, prolactin, testosterone and DHEAS concentrations were found in any of the groups before and after treatment. Leptin level correlated positively with body mass, BMI and hip and waist circumferences in all groups. There were no correlations between leptin and WHR in the pre- and postmenopausal groups. In the premenopausal group and in some postmenopausal groups, serum leptin level correlated with blood pressure. CONCLUSIONS: Endogenous E(2) and androgens in premenopausal women and estrogen and estrogen-progestin therapies in postmenopausal subjects do not influence serum leptin concentrations. Leptin level is related to body mass and BMI, but not to sex hormone status. The distribution of adipose tissue and the type of obesity (android or gynoid) have no influence on serum leptin concentration. The correlation between serum leptin level and blood pressure requires further investigation.     

Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy

OBJECTIVE: To determine serum parameters reflective of androgen status in postmenopausal women using two types of hormone replacement therapy (HRT). DESIGN: Randomized, double-blind, prospective 1-year trial of two oral HRT regimens. SETTING: University hospital, department of obstetrics and gynecology, menopause clinic. PATIENT(S): 100 postmenopausal women > or = 45 years. INTERVENTION(S): Daily use of the progestogen tibolone (2.5 mg; n = 50) or continuous combined 17-beta-estradiol (2 mg) and norethindrone acetate (E+NA, 1 mg; n = 50). MAIN OUTCOME MEASURE(S): Measurements of total testosterone (total T), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), FSH, and sex-hormone-binding globulin (SHBG), and calculations of free testosterone (free T). Assessment of changes from baseline within and between groups after 6 and 12 months. RESULT(S): We found significant differences (% changes) in the tibolone group compared to baseline within the groups after both 6 and 12 months, respectively. Levels of free T doubled, total T decreased slightly, and SHBG decreased by half; DHEAS increased by approximately 20%; and FSH decreased. In the E+NA group, levels of free T, total T, androstenedione, and FSH all decreased, and SHBG increased. Pre-trial levels of DHEAS, A, and total T were significantly higher in the E+NA group. Between groups throughout the study, the changes from baseline were significant due to the different extent of FSH reduction, and opposite changes of free T, SHBG, and DHEAS. CONCLUSION(S): Both regimens modify plasma androgens, DHEAS, and SHBG differently. Tibolone decreased the levels of SHBG, and substantially increased free T and to a lesser extent increased DHEAS; this may reflect a modification of adrenal androgen production. Continuous combined estradiol and norethindrone acetate HRT suppressed the peripheral plasma androgens mediated by increased levels of SHBG.     

Basal hormone levels in women with recurrent pregnancy loss.

The potential role of endocrine abnormalities during the follicular phase in women with unexplained recurrent pregnancy loss was investigated in a retrospective study. Eighty women with recurrent pregnancy loss underwent routine work-up to exclude known associations with the condition. Following investigation, 58 women failed to reveal an identifiable cause, and were therefore classified as having unexplained recurrent pregnancy loss. The control group consisted of women with known causes of abortions, such as uterine septum and parental chromosomal abnormalities. Mean age, gravidity, parity, presence of infertility, previous number of miscarriages and duration of marriage were similar in both groups. Day-3 serum levels of follicle stimulating hormone (FSH), estradiol, luteinizing hormone (LH) prolactin, total testosterone, dehydroepiandrosterone sulfate (DHEAS) and thyroid stimulating hormone (TSH) were compared in the two groups. FSH, estradiol, LH, prolactin and DHEAS concentrations were significantly higher in the unexplained recurrent pregnancy loss group than in the explained recurrent pregnancy loss group, although serum concentrations of all hormones were within the normal range (p < 0.01). TSH and total testosterone levels were similar in the two groups (p > 0.05). There were no differences in the frequency of abnormal levels of hormones between the two groups (p > 0.05). We conclude that endocrine abnormalities in the follicular phase are not associated with recurrent pregnancy loss.     

Serum levels of 3alpha-androstanediol glucuronide in young women with polycystic ovary syndrome, idiopathic hirsutism and in normal subjects

OBJECTIVE: The study objective was to assess the role of 3alpha-androstanediol glucuronide (3alpha-diolG) as the marker of peripheral androgen action in the young women with hirsutism diagnosed as polycystic ovary syndrome (PCOS), in patients with idiopathic hirsutism (IH) and in normal non-hirsute women. STUDY DESIGN: Fifty-nine young women with mean age 21.90+/-3.52 years suffered from hirsutism were included in the study. Among these 59 hirsute women 31 women with mean age 21.60+/-3.56 years were diagnosed as PCOS and 28 women with mean age 22.20+/-3.59 years were classified as idiopathic hirsutism patients. Twenty-seven normal women, age-matched (mean age 22.60+/-2.90 years), without signs of hirsutism and with normal menstrual cycle served as control for this study. Serum was collected from women with hirsutism (due to PCOS or idiopathic hirsutism) and from non-hirsute women. Serum levels of 3alpha-androstanediol glucuronide (3alpha-diolG), main androgens such as: testosterone, free testosterone, dehydroepiandrosterone (DHEAS) and also others hormones such as follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2) and sex hormone-binding globuline (SHBG) were measured using radioimmunoassay (RIA) method in the study and control group. Hirutism was assessed using modified Ferriman-Gallwey method. Serum 3alpha-diolG levels in PCOS women were significantly higher than in controls. RESULTS: There were no significant differences between serum 3alpha-diolG levels in PCOS group and IH group. Similarly, there were significant differences between serum 3alpha-diolG levels in IH group and control subjects. CONCLUSION: We conclude that 3alpha-diolG is not useful as the marker for peripheral androgen metabolism and for differentiation between idiopathic hirsutism and PCO-related hirsutism.     

Endocrine, neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women.

Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (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, androstenedione, 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, androstenedione, 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.     

Effect of soy supplementation on endogenous hormones in postmenopausal women

AIM: The purpose of this study was to investigate the effect of soy supplementation with isoflavones on plasma hormone levels in postmenopausal women. METHODS: 16 postmenopausal women (mean age 56.21 +/- 5.01 years) were assigned to 24 weeks of dietary soy supplementation. A defined soy protein amount per day (20 g) with a low dosage of isoflavones (20 mg) was used. Plasma samples were analyzed for estradiol, FSH, LH, prolactin, testosterone and DHEAS. RESULTS: After 24 weeks of soy supplementation, plasma levels of estradiol did not increase. Gonadotropins, prolactin and the measured plasma androgens remained unchanged. We did not see any significant treatment effects. CONCLUSIONS: In the postmenopausal hypoestrogenic situation, soy protein consumption with low isoflavones does not influence endogenous hormone levels of estradiol and gonadotropins.     

The androgenic profile of women with non-insulin-dependent diabetes mellitus

OBJECTIVE: To evaluate the androgenic profile of women with non-insulin-dependent diabetes mellitus. STUDY DESIGN: This case-control study evaluated the clinical, hormonal and ultrasonographic characteristics of women of reproductive age with non-insulin-dependent diabetes mellitus and compared them with those of age- and weight-matched controls. Radioimmunoassays were used for total testosterone, estradiol, dehydroepiandrosterone sulfate (DHEAS) and androstenedione. Sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and follicle stimulating hormone (FSH) were analyzed by fluoroimmunoassays. Ovarian appearance and volume were assessed by transvaginal or transabdominal ultrasonography. RESULTS: The prevalence of polycystic ovary syndrome was higher in diabetic patients than in the general population as reported earlier. Hirsutism was also more prevalent in diabetic patients (p < 0.05). The serum levels of FSH, LH, estradiol, total testosterone, androstenedione and DHEAS were significantly higher in diabetic patients than in the control group (p < 0.05). In contrast, the levels of SHBG were lower in diabetic patients (p < 0.05). The rates of ultrasonographically apparent polycystic ovaries and greater ovarian volumes were also higher in diabetic patients (p < 0.05). CONCLUSION: Women with non-insulin-dependent diabetes mellitus seem to have biochemical and clinical hyperandrogenism when compared with nondiabetic controls.     

Endocrine,neuroendocrine and behavioral effects of oral dehydroepiandrosterone sulfate supplementation in postmenopausal women

Aging in women and men is characterized by a progressive decline of circulating dehydroepiandrosterone (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 β-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 μg/patch) and the third with transdermal estradiol alone (n = 6) (50 μg/day). Before and after 1 ,2 and 3 months of therapy ,the following circulating steroid and protein hormone levels were evaluated: DHEA ,DHEAS ,androstenedione ,testosterone ,estrone ,estradiol ,17-hydroxyprogesterone ,sex hormone-binding globulin (SHBG) ,follicle-stimulating hormone (FSH) ,luteinizing hormone (LH) ,β-endorphin ,growth hormone (GH) and Cortisol ,and a Kupperman score was performed. Before and after treatments ,plasma β-endorphin levels were evaluated in response to three neuroendocrine tests: (a) clonidine ,an a₂-presynaptic adrenergic agonist (1.25 mg IV); (b) naloxone ,an opioid receptor antagonist (4 mg IV) and (c) fluoxetine ,a serotonin selective reuptake inhibitor (30 mg PO).

In both groups of women treated with DHEAS ,mean basal serum DHEA ,DHEAS ,androstenedione ,and testosterone levels significantly increased after treatment ,while no changes were shown in the group receiving estradiol alone. Serum estradiol ,estrone ,GH and plasma β-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 β-endorphin levels. After each of the treatments ,the β-endorphin response was completely restored and was similar ,independent of the kind of therapy.

Restoration of the β-endorphin response to specific stimuli suggests that DHEAS and/or its active metabolites modulates the neuroendocrine control of pituitary β-endorphin secretion ,which may support the therapeutic efficacy of the DHEAS on behavioral symptoms.     

Basal hormone levels in women with recurrent pregnancy loss

The potential role of endocrine abnormalities during the follicular phase in women with unexplained recurrent pregnancy loss was investigated in a retrospective study. Eighty women with recurrent pregnancy loss underwent routine work-up to exclude known associations with the condition. Following investigation ,58 women failed to reveal an identifiable cause ,and were therefore classified as having unexplained recurrent pregnancy loss. The control group consisted of women with known causes of abortions ,such as uterine septum and parental chromosomal abnormalities. Mean age ,gravidity ,parity ,presence of infertility, previous number of miscarriages and duration of marriage were similar in both groups. Day-3 serum levels of follicle stimulating hormone (FSH) ,estradiol ,luteinizing hormone (LH) prolactin ,total testosterone, dehydroepiandrosterone sulfate (DHEAS) and thyroid stimulating hormone (TSH) were compared in the two groups. FSH ,estradiol ,LH ,prolactin and DHEAS concentrations were significantly higher in the unexplained recurrent pregnancy loss group than in the explained recurrent pregnancy loss group ,although serum concentrations of all hormones were within the normal range (p < 0.01). TSH and total testosterone levels were similar in the two groups (p > 0.05). There were no differences in the frequency of abnormal levels of hormones between the two groups (p > 0.05). We conclude that endocrine abnormalities in the follicular phase are not associated with recurrent pregnancy loss.     

A relationship between sex hormone binding globulin and dehydroepiandrosterone sulfate in normally menstruating females

Blood samples were collected from 120 normally menstruating women throughout the menstrual cycle. Serum was assayed for sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), estradiol (E2) and testosterone (T). There was an inverse relationship between SHBG and DHEAS, but no relationship between T or E2 and SHBG levels. There is at present no model which readily explains this inverse relationship between SHBG and DHEAS in normal subjects.     

High levels of serum allopregnanolone in women with premature ovarian failure

The endocrine characteristics of patients with premature ovarian failure (POF) have not been fully elucidated. The aim of the present study was to evaluate whether steroidogenic activity in women with POF is different with respect to fertile and postmenopausal subjects.

In particular, circulating levels of allopregnanolone, a neuroactive steroid involved in modulation of reproductive function in rats, have been evaluated and correlated with serum levels of Δ4 precursor (dehydroepiandrosterone sulfate (DHEAS)), A5 intermediates (androstenedione, 17-hydroxyprogesterone (17-OHP), progesterone) and final products (estradiol and testosterone) of androgens. Levels of luteinizing hormone (LH), follicle stimulating hormone (FSH) and sex hormone binding globulin (SHBG) were also determined. In all cases specific radioimmunological assays were used. Women with POF showed statistically significantly lower concentrations of 17-OHP, androstenedione and testosterone when compared to fertile controls, while no differences were found between women with POF and postmenopausal women. Serum DHEAS levels were similar in POF patients and in fertile controls and higher with respect to postmenopausal women. Serum allopregnanolone levels were significantly higher in women with POF than in postmenopausal and infertile women. A significant inverse correlation between allopregnanolone levels and menopausal age in patients with POF was observed while no significant correlation was found between allopregnanolone and progesterone, androstenedione, 17-OHP and testosterone levels. In conclusion, allopregnanolone is scarcely influenced by the reduction of ovarian and adrenal activity observed in POF.     

Role of the follistatin gene in women with polycystic ovary syndrome

OBJECTIVE: To search for mutations in the coding exons of the follistatin gene of women diagnosed with polycystic ovary syndrome (PCOS). DESIGN: Controlled clinical study.Setting: Tertiary institutional hospital. PATIENT(S): Thirty-four women diagnosed with PCOS and 15 healthy control women. INTERVENTION(S): Whole blood and serum samples were collected during the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURE(S): Circulating total testosterone (T), sex hormone-binding globulin (SHBG), calculated free T (FT), androstenedione (A), dehydroepiandrosterone-sulfate (DHEAS), LH, FSH, E2, and basal and adenocorticotropic hormone (ACTH)-stimulated 17-hydroxyprogesterone (17-OHP) were determined. Insulin resistance was estimated from fasting glucose and insulin levels, using the homeostasis model assessment. The coding regions of the follistatin gene were studied by heteroduplex analysis after polymerase chain reaction amplification. RESULT(S): Women with PCOS presented with higher body-mass index, insulin resistance, T, FT, A, and ACTH-stimulated 17-OHP serum concentrations and lower SHBG serum levels, as compared with controls. No differences were observed among the groups in serum DHEAS, basal 17-OHP, E(2), LH, and FSH. No mutations were found in coding regions of the follistatin gene, with the exception of a G to A change at cDNA position 951, resulting in a silent mutation. This change was present in 2 (5.9%) of 34 patients and 1 (6.7%) of 15 controls. CONCLUSION(S): Mutations in the coding regions of the follistatin gene do not appear to be related to PCOS.     

Bone mineral density in women with idiopathic hirsutism.

Idiopathic hirsutism is relatively uncommon, affecting approximately 6% of hirsute women. In the present study we compared the bone mineral density (BMD) of women with idiopathic hirsutism with controls. A group of 20 women diagnosed with idiopathic hirsutism was evaluated with respect to BMD and the findings were compared to those of a control group consisting of 10 normal women. Hirsutism was graded according to the Ferriman-Gallwey score and threshold was considered to be a score more than 4. There was no statistically significant difference with respect to patients' mean age, BMI and body fat composition. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), androstenedione, testosterone, free testosterone, 17 alpha-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone binding globulin (SHBG) and estradiol were assessed in both groups and no statistically significant differences were found. There was no statistically significant difference with respect to bone turnover--which was evaluated by determining the serum levels of parathyroid hormone, calcium, alkaline phosphatase and osteocalcin as well as the urinary secretion of calcium and hydroxyproline, corrected for the creatinine values--between the two groups. Statistical analysis was performed using the t test for unpaired data to compare age, BMD and biochemical data, and Wilcoxon's rank test was used to compare physical activity and calcium intake. Statistical significance was defined as p < 0.05. The BMD at the level of the 2nd to 4th lumbar vertebrae (L2-L4) and the total BMD were higher in women with idiopathic hirsutism compared to those in the control group, suggesting a possible direct effect of androgens on the osseous tissue of hirsute women.