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Objective To test the hypothesis that the polycystic ovary syndrome (PCOS) phenotype, or its component features, is less severe in adolescents than in young adult patients, in a referred (clinical) population. Design Cross-sectional study. Setting Tertiary-care academic medical center. Patient(s) Two hundred seventy-four adolescents and young adults aged 13.0–24.9 years with PCOS according to the National Institute of Health 1990 criteria. Patients were categorized as adolescents (AD: 13.0–18.9 years; n=91) and young adults (YA: 19.0–24.9 years; n=183). Adolescents were further categorized as early adolescents (Early-AD: 13.0–15.9 years; n=31) and late adolescents (Late-AD: 16.0–18.9 years; n=60). Intervention(s) History, physical examination, hormonal assays with the use of standardized protocols. Main Outcome Measure(s) Unadjusted and adjusted odds ratios (ORs; adjusted for body mass index [BMI] when applicable) were calculated for biochemical hyperandrogenism (HA), hirsutism (HIR), acne, and degree of oligo/amenorrhea (OA). PCOS phenotypes were classified as HIR+HA+OA, HA+OA, and HIR+OA. Result(s) Our analysis demonstrated minimal significant difference in the prevalence of the three PCOS phenotypes, or component features, between AD and YA patients. The risks for obesity were higher for YA versus AD, and the risk of acne was lower for YA versus AD. There was no significant difference between Early-AD and Late-AD. BMI-adjusted models did not significantly modify the main findings. Conclusion(s) The present study suggests that the PCOS phenotype is established in early adolescence, remains constant into adulthood, and is not related to BMI.

Objective To test the hypothesis that women with polycystic ovary syndrome (PCOS) are distinguishable from those with 21-hydroxylase–deficient nonclassic adrenal hyperplasia on the basis of having polycystic ovaries and metabolic dysfunction. Design Prospective observational. Setting Tertiary care center. Patient(s) Fifty-two lean and 54 obese women with PCOS according to the 1990 National Institutes of Health criteria, 23 women with nonclassic adrenal hyperplasia, and 27 controls. Intervention(s) History and physical examination, blood sampling, ovarian sonography, oral glucose tolerance, and acute adrenocorticotropin stimulation testing. Main Outcome Measure(s) The frequency of clinical, biochemical, and metabolic features. Result(s) Women with PCOS had a higher frequency of oligomenorrhea or amenorrhea than those with nonclassic adrenal hyperplasia. Mean androstenedione and DHEAS levels were highest in nonclassic adrenal hyperplasia. The degree of metabolic dysfunction was greatest in obese women with PCOS; women with nonclassic adrenal hyperplasia and lean women with PCOS did not differ in degree of metabolic dysfunction. Women with nonclassic adrenal hyperplasia had a lower prevalence of polycystic ovaries than those with PCOS. The proportion of patients with an LH/FSH ratio >2 was greater in women with PCOS, compared with those with nonclassic adrenal hyperplasia. Basal 17-hydroxyprogesterone levels >2 ng/mL were found in 87%, 25%, 20%, and 7% of women with nonclassic adrenal hyperplasia, lean women with PCOS, obese women with PCOS, and controls, respectively. Conclusion(s) Nonclassic adrenal hyperplasia should be excluded in all women presenting with hirsutism, with use of a basal follicular phase 17-hydroxyprogesterone level, regardless of the presence of polycystic ovaries or metabolic dysfunction; however, women with nonclassic adrenal hyperplasia have a higher prevalence of normal ovulation and lower likelihood of having an LH/FSH ratio >2 or polycystic ovaries.

Objective To determine the level of plasma soluble CD40 ligand (sCD40L) in patients with polycystic ovary syndrome (PCOS). Design Prospective study. Setting Baskent University School of Medicine in Turkey. Patient(s) Thirty-one patients with PCOS and 31 non-PCOS (control) patients. Intervention(s) Determination of plasma sCD40L and homocysteine levels. Main Outcome Measure(s) Plasma sCD40L, fasting glucose, fasting insulin, homeostatic model assessment insulin resistance index (HOMA-IR), LH, FSH, E 2 , total T, DHEAS, total cholesterol, high- and low-density lipoprotein cholesterol, triglyceride, homocysteine, and high-sensitivity C-reactive protein (hsCRP). Result(s) The mean serum fasting insulin and HOMA-IR levels were significantly higher in the PCOS group. The mean serum homocysteine level was significantly higher in the PCOS group. Despite a trend for higher high-sensitivity C-reactive protein levels in the PCOS group, the difference did not reach statistical significance. The mean plasma sCD40L level in the PCOS group was significantly higher than that in the control group (5.14 ± 3.65 ng/mL vs. 3.45 ± 2.64 ng/mL, respectively). Conclusion(s) Polycystic ovary syndrome is associated with elevated levels of sCD40L and homocysteine.

Objective To test the interdependence between insulin resistance (IR) and gonadotropin dissociation (GD) in polycystic ovary syndrome (PCOS). Design Cross-sectional prospective study. Setting Clinical research center. Patient(s) Thirty-two PCOS patients aged 19–34 years; 16 obese (BMI ≥ 27) and 16 nonobese (BMI Intervention(s) A 75-g oral glucose tolerance test (OGTT) and a 100-μg i.v. GnRH test were performed on different days. Blood was taken at 0, 30, 60, 90, 120, and 180 minutes in each test. Serum glucose, insulin, LH, and FSH were measured. Main outcome measure(s) Area under the curve was calculated for glucose, insulin, and glucose-to-insulin ratio (GIR), and for LH, FSH, and LH-FSH ratio. Result(s) Glucose, insulin, and GIR were not modified significantly during the GnRH test, nor LH, FSH and LH-FSH ratio throughout the OGTT. There were no significant differences in GIR response of patients with and without GD, nor in LH-FSH ratio of patients with and without IR, after OGTT and GnRH test. However, obese patients with IR had a significantly larger ( P Conclusion(s) Insulin resistance and GD do not appear to be related events in PCOS, suggesting that each one might be determined by different genetic disorders. However, IR can affect GD after chronic stimulation in obese patients.

Objective: To establish whether initial screening characteristics of normogonadotropic anovulatory infertile women can aid in predicting live birth after induction of ovulation with clomiphene citrate (CC). Design: Prospective longitudinal single-center study. Setting: Specialist academic fertility unit. Patient(s): Two hundred fifty-nine couples with a history of infertility, oligoamenorrhea, and normal follicle-stimulating hormone (FSH) concentrations who have not been previously treated with any ovulation-induction medication. Intervention(s): 50, 100, or 150 mg of oral CC per day, for 5 subsequent days per cycle. Main Outcome Measure(s): Conception leading to live birth after CC administration. Result(s): After receiving CC, 98 (38%) women conceived, leading to live birth. The cumulative live birth rate within 12 months was 42% for the total study population and 56% for the ovulatory women who had received CC. Factors predicting the chances for live birth included free androgen index (testosterone/sex hormone–binding globulin ratio), body mass index, cycle history (oligomenorrhea versus amenorrhea), and the woman's age. Conclusion(s): It is possible to predict the individual chances of live birth after CC administration using two distinct prediction models combined in a nomogram. Applying this nomogram in the clinic may be a step forward in optimizing the decision-making process in the treatment of normogonadotropic anovulatory infertility. Alternative first line of treatment options could be considered for some women who have limited chances for success.

To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome (PCOS).Prospective pilot study.Outpatient.Twenty-two previously oligoamenorrheic, nondiabetic women with PCOS; 125 women with PCOS who were not currently pregnant and who hador = 1 previous pregnancy while they were not receiving metformin.Metformin, 1.5-2.55 g/day, throughout pregnancy.Rates of first-trimester spontaneous abortion and teratogenicity.Before metformin, 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions (73%). While receiving metformin, these 10 women had 6 normal live births (60%), 1 spontaneous abortion (10%), and 3 normal ongoing pregnancies (30%) (allor = 13 weeks; median gestation, 23 weeks). Among women receiving metformin, including those with live births and normal pregnancy for at least the first trimester, 1 of 10 (10%) had first-trimester spontaneous abortion compared with 73% in 22 previous pregnancies without metformin (P.002). To date, the 19 women receiving metformin have had no adverse maternal side effects, and no birth defects have occurred; 9 (47%) had normal term live births, 2 (11%) had normal and appropriate for gestational age births (one at 33 and one at 35 weeks), 6 (32%) have ongoing normal pregnancies lasting longer than the first trimester, and 2 (10.5%) had first-trimester spontaneous abortions. Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies (median gestation, 23 weeks). Among women who received metformin before conception, reductions in insulin and plasminogen activator inhibitor activity were correlated (r=0.65, P=.04).Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic.

Objective: To evaluate [1] the effects of levels of sex hormone-binding globulin (SHBG), albumin, and total testosterone on the distribution of testosterone between SHBG-bound and non–SHBG-bound fractions; [2] the independent effects of polycystic ovary syndrome (PCOS) and body mass index on serum levels of total testosterone, non–SHBG-bound testosterone, SHBG, and albumin; and [3] the usefulness of levels of total testosterone and non–SHBG-bound testosterone and of the free androgen index in the diagnosis of PCOS. Design: Retrospective clinical study. Setting: An academic research environment. Patient(s): Forty-three women with oligomenorrhea and PCOS. Twenty-five women with regular menstrual cycles and without hirsutism served as controls. Intervention(s): None. Main Outcome Measure(s): Levels of non–SHBG-bound testosterone, total testosterone, SHBG, and albumin in serum. Result(s): Levels of total testosterone and non–SHBG-bound testosterone, and the free androgen index were higher in patients with PCOS than in healthy controls. PCOS did not have an effect on the levels of SHBG or albumin, or on the percentage of non–SHBG-bound testosterone. Levels of SHBG and albumin were inversely related to body mass index. The percentage and concentration of non–SHBG-bound testosterone and the free androgen index were directly related to body mass index. Hirsutism did not have an effect on any outcome measure. Conclusion(s): The distribution of total testosterone into SHBG-bound and non–SHBG-bound fractions is associated with body mass index, not with PCOS. The high levels of non–SHBG-bound testosterone and the high free androgen index in patients with PCOS reflect mainly high levels of total testosterone. Thus, the measurement of levels of non–SHBG-bound testosterone and the calculation of the free androgen index provide no further information in the diagnosis of PCOS beyond that provided by the measurement of levels of total testosterone.

Objective To examine the serum total renin in women with polycystic ovarian syndrome (PCOS) and in controls. Setting Outpatient clinic of reproductive endocrinology at Turku University Central Hospital, Turku, Finland. Patients Forty-four oligomenorrheic women with PCOS (body mass index [BMI] 18.0 to 49.0 kg/m 2 ) and 25 control women with regular menstrual cycles (BMI 18.0 to 53.5 kg/m 2 ). Main Outcome Measures The concentrations of total renin, LH, FSH, T, androstenedione (A), sex hormone-binding globulin (SHBG), and insulin in serum. Results The concentration of total renin in serum was higher in PCOS women than in healthy women independently of BMI, age, or serum insulin. The serum total renin measurement discriminated PCOS patients and control women to a similar extent as the previously used hormonal parameters (LH:FSH, T, A, and T:SHBG) as judged by receiver-operating characteristic analysis. Positive correlations were found between the serum total renin level and LH concentration, LH:FSH ratio, T and A levels, and T:SHBG ratio. Analysis of serum total renin in PCOS patients during oligomenorrhea and after menstruation did not reveal any significant changes. Conclusions The elevated concentration of serum total renin suggests an enhanced activity of ovarian renin-angiotensin system in PCOS. The determination of serum total renin may provide a novel tool in the diagnostics of PCOS, because its serum level is elevated in PCOS women independently of BMI and serum insulin.

Objective To examine the prevalence of the metabolic syndrome (MetS) according to the scientific statement of the American Heart Association and the US National Cholesterol Education Program/Adult Treatment Panel III in middle-aged Swedish women previously diagnosed with polycystic ovary syndrome (PCOS) in comparison with age-matched healthy controls. Design Long-term follow-up study. Setting Department of Obstetrics and Gynecology, Uppsala University. Patient(s) Eighty-four women diagnosed with PCOS between 1987 and 1995; and 87 controls randomly selected from the general population. Intervention(s) Anthropometric measurements and blood tests. Main Outcome Measure(s) Body mass index, waist circumference, blood pressure, lipids, and glucose. Result(s) The prevalence of MetS in women with PCOS (mean ± SD age, 43.0 ± 5.8 years) was 23.8% and in controls was 8.0%, and it did not differ according to PCOS phenotype at the index assessment (polycystic ovaries [PCO], oligomenorrhea, and hirsutism: 10 [22.7%]; PCO and oligomenorrhea: 8 [22.2%]) or according to the persistence of PCOS features at follow-up (persisting PCOS: 25.8%; resolved PCOS: 16.7%). Conclusion(s) The MetS occurred more often in patients with PCOS than in controls and did not depend on phenotypic presentation at the index assessment or the persistence of PCOS at follow-up.

Objective To evaluate the performance of antimullerian hormone (AMH) and inhibin B as ovarian function markers for differentiating common causes of secondary oligoamenorrhea, namely hypogonadotrophic hypogonadism (HH), polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and hyperprolactinemia (HPRL). Design Retrospective analysis. Setting Two university hospitals. Patient(s) A total of 124 women with secondary oligoamenorrhea and 26 women with normal ovulation. Intervention(s) Serum samples from the subjects were analyzed for AMH and inhibin B. Main Outcome Measure(s) Serum AMH and inhibin B concentrations. Result(s) Serum AMH concentration was significantly raised in women having World Health Organization group 2 anovulation, either with or without PCOS, and was significantly decreased to very low levels in POF; the diagnostic accuracy in both conditions was excellent, with areas under the receiver operating characteristic curve (AUC) of 0.913 and 0.977, respectively. The discriminatory performance between HH and PCOS was also good, with AUC 0.861. AMH remained unchanged in HH and HPRL compared with ovulatory control subjects. There were large overlap of serum inhibin B levels in the different conditions, and a significant difference from control subjects existed only in the POF group. Conclusion(s) Serum AMH, but not inhibin B concentration, serves as a useful diagnostic tool in the differential diagnosis of secondary oligoamenorrhea.

Objective To examine the clinical efficacy of low dose spironolactone in hirsute women. Design Retrospective. Setting Outpatient endocrinology clinic. Patients One hundred nine consecutive women prescribed 75 to 100 mg/d spironolactone for at least 4 months in whom adequate follow-up data were available. Results Hirsutism improved in 72% of the women. Women with regular menses, whether or not they used oral contraceptives (OCs), had the highest response rate to spironolactone (78%), whereas women with irregular menses who did not use an OC had the lowest response rate (55%). Favorable responses were associated with increased severity of hirsutism (P = 0.04) and lower serum dehydroepiandrosterone sulfate levels (P = 0.05). Responders and nonresponders did not differ significantly in age (P = 0.10), duration of hirsutism (P = 0.14), pretreatment serum testosterone (T) (P = 0.48), or body mass index (P = 0.11). However, when each parameter was divided into subsets, trends toward decreasing response were observed with increasing age, duration of hirsutism over 15 years, and increasing serum T level. Conclusion Low-dose spironolactone improves hirsutism in a majority of hirsute women, irrespective of age, severity or duration of hirsutism, menstrual status, or serum hormone levels.

Objective To study the differences in clinical and biochemical characteristics between obese and nonobese women with polycystic ovary syndrome (PCOS). Design Retrospective study. Setting University teaching hospital. Patient(s) Four hundred sixty-four Taiwan Chinese women, among whom 295 were diagnosed with PCOS and 169 were non-PCOS controls. Main Outcome Measure(s) Body mass index, average menstrual interval, modified Ferriman-Gallwey score, acne, total T, and waist-to-hip ratio. Result(s) Obese women with polycystic ovary morphology (PCOM) had a greater risk of developing of PCOS (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.5–10.4) than nonobese women with PCOM. Obese women with PCOM had a higher incidence oligomenorrhea (OR, 2.6; 95% CI, 1.6–4.1) and biochemical hyperandrogenemia (OR, 2.5; 95% CI, 1.6–4.0) than nonobese women with PCOM. Obese subjects with PCOS had a higher risk of developing oligomenorrhea (OR, 2.2; 95% CI, 1.3–3.7) and biochemical hyperandrogenemia (OR, 2.6; 95% CI, 1.6–4.2) than nonobese women with PCOS. Moreover, obese women with PCOS had significantly higher serum total T levels and more prolonged menstrual intervals than nonobese women with PCOS. Notably, the obese women with PCOS presented less acne than the nonobese subjects (OR, 0.5; 95% CI, 0.3–0.9). Conclusion(s) Obese women with PCOS had more severe ovulatory dysfunction and higher serum total T levels than nonobese subjects. Moreover, obese women with PCOS had a significantly lower frequency of acne than nonobese subjects.

Objective To determine whether infertile oligomenorrheic women are insulin resistant, using an oral glucose tolerance test (OGTT). Design Retrospective study. Setting National Center for Child Health and Development. Patient(s) One hundred twenty-seven infertile women with oligomenorrhea (oligomenorrheal group) and 177 infertile eumenorrheic women (normal menstrual group) were recruited. Intervention(s) All women underwent an OGTT (75 g glucose). Main Outcome Measure(s) A homeostasis model assessment of insulin resistance (HOMA-IR), area under the curve (AUC) of insulin after the glucose load, and plasma insulin level at 120 minutes after glucose loading (IRI 120) were used as an index of insulin resistance. Result(s) The prevalence of insulin resistance (HOMA-IR ≥1.73) among oligomenorrheic women was 23.8%, which was significantly higher than that of eumenorrheic women, at 14.1%. The glucose AUCs (mean ± SE) in the oligomenorrheal group (13,609 ± 259 mg/min/dL) were similar to those for the normal menstrual groups (13,054 ± 196 mg/min/dL), but the insulin AUCs of the oligomenorrheal group (5333 ± 376 mU·min/L) were significantly higher than those of the normal menstrual groups (4517 ± 266 mU·min/L). Conclusion(s) The prevalence of insulin resistance assessed using an OGTT was significantly higher among infertile oligomenorrheic women with non-polycystic ovary syndrome than it was among women with normal menstrual cycles.

Polycystic ovary syndrome (PCOS) is one of the major causes of adolescent hyperandrogenism and menstrual disorders. Because there is no universal definition for adolescent PCOS, we recommend four out of five criteria: clinical and biologic evidence of hyperandrogenism, hyperinsulinism, oligo-/amenorrhea, and polycystic ovaries on ultrasonography.

Objective To determine whether obese, nonhirsute adolescents with oligomenorrhea exhibit similar increased LH pulse secretion patterns compared with obese girls with polycystic ovary syndrome (PCOS). Design Prospective, observational study. Setting Tertiary university hospital. Patient(s) Nine obese girls with oligomenorrhea, 15 with PCOS, and 10 controls. Intervention(s) Twenty-four-hour IV blood sampling for LH (every 10 minutes); measurement of steroid hormones (every 12 hours); and injection of leuprolide acetate (10 μgm/kg SC). Main Outcome Measure(s) Twenty-four-hour, wake, and sleep LH mean serum concentration, pulse frequency, amplitude; steroid hormones, including free androgen index (FAI); and pre- and post-leuprolide acetate 17-hydroxyprogesterone measurements. Result(s) Twenty-four-hour LH pulse frequency in oligomenorrheic girls (18.6 ± 1.2) (mean ± SE) was comparable to that in girls with PCOS (20.9 ± 0.7) and greater than in normal girls (13.4 ± 0.8). The pulse number during both sleep and wake was identical in oligomenorrheic and PCOS girls and significantly greater than that of normal girls. Mean 24-hour LH level, serum androgen levels, and FAI in oligomenorrheic girls were equivalent to those of normal controls and lower than those of PCOS girls. Conclusion(s) These preliminary results indicate that obese girls with oligomenorrhea exhibit increased LH pulse frequency in the absence of clinical and/or biochemical evidence of hyperandrogenism.

Objective To report the successful use of gadolinium radiologic contrast for hysterosalpingography. Design Case report. Setting Outpatient care in a private practice setting. Patient(s) One female patient entering and finishing study. Intervention(s) Hysterosalpingogram. Main Outcome Measure(s) Interpretability of radiological imaging. Result(s) Visualization of a normal uterine cavity and fallopian tubes with bilateral patency was confirmed during the procedure. Radiologic films were created that document the results. The best visualization of the internal pelvic anatomy was noted during the actual procedure. There was a lighter image noted on the films taken from the use of gadolinium rather than the traditional iodinated contrast. Conclusion(s) Gadolinium is a safe and useful alternative to iodinated contrast for hysterosalpingography in patients with iodine allergy.

To evaluate endocrine mechanisms underlying oligomenorrhea or amenorrhea in female athletes.Cross-sectional study.Women's health clinical research unit at a university hospital.Age- and BMI-matched groups of athletes active in endurance sports with and without menstrual disturbances and regularly cycling sedentary controls.Groups were compared with respect to endocrine status, body composition, and physical performance.Identification of a subgroup of oligomenorrheic or amenorrheic athletes with increased androgen levels and anabolic body composition.A subgroup of 8 of 25 athletes with menstrual disturbances had significantly higher serum levels of free and total testosterone, androstenedione, LH-FSH ratio, and lower SHBG levels than did all other groups. Other oligomenorrheic or amenorrheic athletes had normal values comparable to those in regularly menstruating athletes and controls. The hyperandrogenic subgroup showed a more anabolic body composition, with higher total bone mineral density and upper-lower fat mass ratio than did oligomenorrheic or amenorrheic athletes with normal androgen levels. The hyperandrogenic subgroup had the highest VO2 max and the highest performance values in general.Menstrual disturbances in female athletes are often explained as a consequence of hypothalamic inhibition and caloric deficiency. We suggest that essential hyperandrogenism is an alternative mechanism underlying oligomenorrhea or amenorrhea in some female athletes and may imply an advantage for physical performance.

Objective: To determine the rate of clinically evident polycystic ovary syndrome (PCOS) among first-degree female relatives within families with a proband affected by PCOS. Design: Clinical and biochemical evaluation of the mothers and sisters of 93 patients with PCOS. The diagnosis of PCOS was established by: [1] a history of oligomenorrhea, [2] clinical evidence (i.e., hirsutism) or biochemical evidence (i.e., elevated total or free T) of hyperandrogenism, and [3] the exclusion of related disorders. Setting: Tertiary care university. Patient(s): Patients with PCOS and their mothers and sisters. Intervention(s): Interview, physical examination, and hormonal testing on blood samples were performed for all subjects. Main Outcome Measure(s): The presence of hirsutism and hyperandrogenemia was determined in the mothers and sisters of the patients with PCOS. Result(s): Of the 78 mothers and 50 sisters evaluated clinically, 19 (24%) and 16 (32%) were affected with PCOS, respectively. A higher rate of PCOS was observed when only premenopausal women not taking hormones (i.e., untreated) were considered (i.e., 35% of mothers and 40% of sisters), consistent with amelioration of symptoms with hormonal therapy or aging. These rates of PCOS are significantly higher than that observed in our general population (approximately 4%) and suggest the involvement of a major genetic component in the disorder. Conclusion(s): The rates of PCOS in mothers and sisters of patients with PCOS were 24% and 32%, respectively, although the risk was higher when considering untreated premenopausal women only.

Objective: To characterize how the menstrual cycle pattern relates to fertility regardless of potential biases caused by inappropriate coital timing during the menstrual cycle or early embryonal loss. Design: Prospective follow-up study. Setting: Healthy couples recruited throughout Denmark. Patient(s): Two hundred ninety-five couples who were planning their first pregnancy were followed up from the discontinuation of birth control until a pregnancy was recognized within six menstrual cycles. Early embryonal losses were detected by changes in urinary hCG levels. Intervention(s): None. Main Outcome Measure(s): The probability of pregnancy occurring within one menstrual cycle (fecundity). Result(s): In women who had a cycle length that differed by >10 days from the usual cycle length, fecundity was approximately 25% that of women who had no variation (odds ratio 0.25, 95% confidence interval 0.09–0.68). When the combined effect of cycle variation and cycle length was assessed, cycle variation was a persistent strong predictor of fecundity. Conclusion(s): The mechanisms of the present findings probably are female functional disturbances in ovulation, conception, implantation, or sustained pregnancy, linked with variable menstrual cycle length. Thus, identification of medical and environmental causes of abnormal menstrual cycle patterns may provide clues to the causes of infertility. Moreover, the menstrual cycle pattern also should be taken into consideration in the clinical decision-making process.

Objectives To investigate the efficacy of hCG in the management of recurrent early pregnancy loss. Design A prospective, randomized, controlled trial. Setting Miscarriage Clinic, Women's Hospital, Liverpool, United Kingdom. Subjects Eighty-one women attending the miscarriage clinic with idiopathic recurrent pregnancy loss were randomized to receive hCG supplementation or placebo in early pregnancy. Main Outcome Measure The success rate or live birth rate. Results In women with regular menstrual cycles it was found that hCG had no beneficial effect, the pregnancy success rate being 86% in both groups. However, women with oligomenorrhea had a pregnancy success rate of 40% in the placebo group but a statistically significant improvement to 86% if hCG was given. Conclusions Human chorionic gonadotropin can be recommended for idiopathic recurrent pregnancy loss in women with oligomenorrhea.

Objective To investigate the effect of dopaminergic drugs on the well being in hyperprolactinemic patients. Design A psychometric test for well being, the SCL-90, was applied at baseline and in the 24th week of a double-blind randomized prospective study comparing the effectiveness and safety of the new dopamine d2 agonist CV 205-502 with bromocriptine. Setting Outpatient department of a university clinic for obstetrics and gynecology. Patients Twenty-four women with hyperprolactinemia, 9 of whom had a prolactinoma. Twenty had been treated before, and 11 were known to react unfavorably to bromocriptine. Results The effectiveness of CV 205-502 was identical to bromocriptine: its tolerability appeared to be better, especially in the initial phase of treatment. At baseline, the mean scores of the SCL-90 were significantly elevated over the reference values. Sixteen patients had normal scores. The elevations were caused by 8 patients with scores in the range found in psychiatric disease (211±30 [SD] [CV 205-502] and 182±32 [bromocriptine]). They were depressed, anxious, and hostile. At 24 weeks, the patients treated with CV 205-502 scored better (130±23.5) in the SCL-90 than the patients treated with bromocriptine (149.5±20). Conclusion The markedly increased well being in patients treated with CV 205-502 cannot be explained by its better tolerability and is probably caused by a specific central activity of CV 205-502. Further research into the antidepressive properties of this compound is warranted.

The present study was undertaken to assess the correlation between and relative predictive value of each of the following variables and progestin-induced withdrawal bleeding: cervical mucus appearance, serum E2 level, patient age, duration of amenorrhea, smoking and exercise habits, and body composition. Of 120 oligomenorrheic and amenorrheic women evaluated, only cervical mucus appearance and serum E2 level were significantly associated with response to progestin challenge. A multivariate logistical regression analysis showed cervical mucus to be the most predictive variable followed by serum E2 level. No absolute E2 level was found to discriminate between those who did and those who did not have withdrawal bleeding after progestin challenge. These data suggest that office examination of cervical mucus may be a useful indicator and guideline in planning therapy.

An extended regimen of clomiphene consisting of 250 mg of clomiphene for 8 days followed by the administration of 10,000 IU of human chorionic gonadotropin (hCG) 6 days later was administered to 13 oligomenorrheic women who had previously failed to ovulate when treated with 250 mg of clomiphene for 5 days and hCG. Eight of these 13 women ovulated. Their postovulatory mean progesterone (P) level 7 days after hCG was 16 +/- 2 ng/ml. Three pregnancies occurred during 25 treatment cycles. Posttreatment estrogen levels were higher when women were treated for 8 days than for 5 days. Women ovulating after 8 days of treatment had increased concentrations of luteinizing hormone (LH) and testosterone (T) prior to hCG administration and higher pretreatment levels of estrogen and T, compared with women who did not ovulate. Changes in the timing of hCG administration may induce ovulation in some women who fail to ovulate when hCG is given on day 14. Because this 8-day regimen of clomiphene and hCG was successful in more than 50% of women failing to ovulate after 5 days, this regimen should be used prior to human menopausal gonadotropin (hMG) therapy.

The effects of endurance running on body composition, menstrual cycles, and gonadotropins were studied in 19 healthy, young, regularly menstruating women. Midfollicular plasma concentrations of unstimulated and gonadotropin-releasing hormone (GnRH)-stimulated luteinizing hormone and follicle-stimulating hormone were examined at baseline and after each subject's weekly mileage had increased 30 miles (delta 30) and 50 miles (delta 50) above baseline. Mean +/- standard error of the mean unstimulated luteinizing hormone and follicle-stimulating hormone did not change significantly. GnRH-stimulated luteinizing hormone was 76.3 +/- 22.0 micrograms/min/ml at baseline and declined to 20.2 +/- 4.5 micrograms/min/ml at delta 50 (P less than 0.02). GnRH-stimulated follicle-stimulating hormone was 28.4 +/- 7.0 micrograms/min/ml at baseline and declined to 9.6 +/- 2.1 micrograms/min/ml at delta 50 (P less than 0.02). There were no significant correlations between changes in body composition and changes in gonadotropin responses. Eighteen subjects developed oligomenorrhea.

Random blood samples were obtained from a group of patients having oligomenorrhea or secondary amenorrhea, who responded to progesterone with uterine withdrawal bleeding, associated with hirsutism (N = 35) or not associated with hirsutism (N = 9). A few blood samples were obtained during the midfollicular phase of normal cycles in age-matched normal females (N = 10) as controls for comparison. Plasma gonadotropins (follicle-stimulating hormone and luteinizing hormone [LH]) and steroid hormones including testosterone (T), androstenedione (A), estradiol (E 2 ), estrone (E 1 ), and progesterone (P) were quantitated by radioimmunoassay. The percentage of free fraction of E 2 and T was determined by equilibrium dialysis at 37° C, and the percentage of T-E 2 -binding globulin (TeBG)-bound fraction of E 2 and T was estimated by the specific steroid displacement-charcoal adsorption technique. The binding capacity of plasma TeBG was measured by the modified Scatchard plot technique. The E 2 :T ratios of concentrations and the binding parameters were also evaluated. The weight (but not height) of hirsute females was significantly higher than that of normal females. Plasma LH, T, A, and E 1 levels were significantly elevated in hirsute females. Plasma T concentrations, including free, index, and total, correlated positively with degree of hirsutism. E 2 :T ratios of concentration also suggested a similar, but negative, correlation. The percentage of free E 2 increased more than the percentage of free T when the percentage of TeBG-bound E 2 decreased more than the percentage of TeBG-bound T in hirsute females. The E 2 :T ratios of the percentage of free and TeBG-bound fractions did not show any correlation with degree of hirsutism. The T-binding capacity of plasma TeBG decreased in hirsute females and was also correlated significantly with degree of hirsutism. The elevated plasma T concentrations (including free, index, and total concentrations) in hirsute females overlapped significantly with that of normal females, thus they failed to discriminate each other.

The fertility in previously sterile women who conceived at least once following hMG/hCG-induced ovulation is investigated. The study comprises 141 women. The cumulative spontaneous pregnancy rate (CSPR) was calculated using life table analysis and was found to be 30.4% after 5 years. The CSPR for subsequent pregnancies reached 91.3% after 5 years. This figure is similar to that of normal parous women, although the study group (previously infertile women) requires a larger exposure period to attain the figure. The spontaneous abortion rate in the hMG/hCG-induced pregnancies was 29%; whereas in subsequent spontaneous pregnancies this rate was 8.8%. This difference in rate was found to be statistically significant, and the possible reasons are discussed.

Twenty-one women 18 to 36 years old, presenting with chronic anovulation, were compared with 10 normally cycling women. The patients were characterized by low progesterone (P) levels (0.93 +/- 0.14 ng/ml versus 15.5 +/- 1.4 in controls), whereas 17 beta-estradiol (E2) was moderately decreased (110.2 +/- 8.3 pg/ml versus 162.8 +/- 14.5 in controls) realizing a relative hyperestrogenism. Basal prolactin (PRL) levels were not elevated (12.1 +/- 0.97 ng/ml versus 9.2 +/- 0.7 in controls), but after thyrotropin-releasing hormone (TRH) stimulation an exaggerated response was observed (114.5 +/- 7 ng/ml versus 55.8 +/- 9 in controls). Patients were treated with bromocriptine (1.25 mg 2 times a day) for 3 months. Fifteen responded with ovulatory cycles, and five became pregnant. Progesterone increased significantly (10.2 +/- 1.3 ng/ml), whereas in patients who did not ovulate P increased only slightly (1.56 +/- 0.18 ng/ml). The particular endocrine profile of these patients (P/E2 imbalance) realizing relative hyperestrogenism may be responsible for the exaggerated PRL response to TRH. Bromocriptine, in reducing this transient, or masked, hyperprolactinemia, allows in many patients the return to ovulatory cycles. This mechanism may be one of the possible pathways leading to chronic functional or organic hyperprolactinemia.

The hormonal profiles and the effect of oral contraceptives (OCs) on 16 oligomenorrheic and 10 regularly menstruating adolescent girls were studied. Testosterone, androstenedione, dehydroepiandrosterone, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex-hormone-binding globulin were determined on blood samples obtained during a control cycle, during OC treatment, and during the follow-up cycle after discontinuation of OC use. The oligomenorrheic girls had significantly higher concentrations of androstenedione and total and free testosterone than regularly menstruating girls during the control cycle. Sex-hormone-binding globulin concentrations were significantly lower in the oligomenorrheic group. Both in oligomenorrheic and regularly menstruating girls OC treatment caused a decrease in the mean concentrations of all hormones, except prolactin, to similar levels. For 2 to 4 weeks after treatment the oligomenorrheic girls had significantly lower levels of androstenedione, total and free testosterone, and luteinizing hormone than before treatment. In the control group there were no significant differences between pretreatment and posttreatment hormone concentrations. The risks and benefits of prescribing OCs for oligomenorrheic adolescent girls are discussed.The hormonal profiles and effect of oral contraceptives (OCs) on 16 oligomenorrheic and 10 regularly menstruating adolescent girls were studies. Testosterone, androstenedione, dehydroepiandrosterone, estradiol, progesterone, luteinizing hormone, follicle stimulating hormone, prolactin, and sex hormone binding globulin were determined on blood samples obtained during a control cycle, during OC treatment, and during the follow-up cycle after OC discontinuation. The oligomenorrheic girls had significantly higher concentrations of androstenedione and total and free testosterone than regularly menstruating girls during the control cycle. Sex hormone binding globulin concentrations were significantly lower in the oligomenorrheic group. Both inoligomenorrheic and regularly menstruating girls, OC treatment caused a decrease in the mean concentrations of all hormones, except prolactin, to similar levels. For 2-4 weeks after treatment, the oligomenorrheic girls had significantly lower levels of androstenedion, total and free testosterone, and luteinizing hormone than before treatment. In the control group, there were no significant differences between pretreatment and posttreatment hormone concentrations. The risks and benefits of prescribing OCs for oligomenorrheic adolescent girls are discussed.

Competitive swimmers were followed over a 2-year period when they trained at different levels of exercise which coincided with distinct changes in their menstrual history. Oligomenorrhea was identified in 5 of 13 of these athletes when they swam approximately 100,000 yards per week. Weight and percentage of body fat were not significantly different between the period of oligomenorrhea and regular menstrual function (P = 0.24). Mean and median levels of luteinizing hormone, follicle-stimulating hormone, prolactin, and 17beta-estradiol were decreased and catechol estrogens and beta-endorphins were increased in serum during the strenuous, when compared with the moderate, training period. The serum levels of the steroid and protein hormones were similar to those of normal cycling, nonexercising control subjects during moderate exercise (60,000 yards per week). The significant differences between beta-endorphins and catechol estrogens during periods of strenuous exercise suggest an explanation for oligomenorrhea in female athletes. These hormonal changes result in hypothalamic anovulation, which appears to be reversible, because the hormone levels and menstrual cycles return to normal when the exercise is reduced.

Thirteen anovulatory oligomenorrheic, hyperandrogenic, and normoprolactinemic women were treated with spironolactone (aldactone) throughout six consecutive menstrual cycles in a dosage of 100 to 150 mg/day. During this treatment a significant decrease in serum luteinizing hormone (LH), testosterone, prolactin, and 17-ketosteroid values were observed that were accompanied by ovulation in 11 women (85%), according to basal body temperature (BBT) and progesterone values. In addition, improvement of hirsutism was observed in 9 (70%) and restoration of regular cycles in 11 (85%) of the patients. The side effects observed were mild and did not lead to interruption of the treatment. Our data suggest that the antiandrogenic properties of spironolactone render it a suitable agent in the treatment of anovulatory, oligomenorrheic, and hyperandrogenic women.

The plasma concentrations of sex hormones were measured in 45 oligomenorrheic and 28 regularly menstruating adolescent girls. Testosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone-binding globulin levels were determined in blood samples collected during one menstrual cycle. The oligomenorrheic girls had significantly higher concentrations of luteinizing hormone, androstenedione, dehydroepiandrosterone-sulfate, and free testosterone than regularly menstruating girls. Sex hormone-binding globulin concentrations were significantly lower in the oligomenorrheic group. The oligomenorrheic girls were not obese. Signs of acne or hirsutism were absent or mild. Sixty-six percent of the oligomenorrheic cycles were ovulatory. The significance of the hormonal findings is discussed.

Luteinizing hormone-releasing hormone (LH-RH), at a dose level of 10 mug, was administered intravenously to 31 patients, 9 with oligomenorrhea and 22 with secondary amenorrhea. A serum luteinizing hormone level higher than 45 mIU/ml at 30 or 45 minutes after injection was considered to be a "positive response" to LH-RH. All 9 patients in the oligomenorrheic group and 11 of the 22 patients with secondary amenorrhea had a "positive" response. The patients were then treated with increasing doses of clomiphene citrate until an ovulatory dose was reached. Eight of the nine patients with oligomenorrhea ovulated with doses of up to 150 mg of clomiphene daily for 5 days. Of the 11 patients in the group with secondary amenorrhea who had a "positive" response to LH-RH, 7 ovulated at a dose of 150 mg (or less) of clomiphene citrate, while only 1 of the 11 patients with a "negative" response ovulated while receiving a similar dosage of clomiphene. These results suggest that a simplified LH-RH test might be of value in selecting the level of therapy for ovulation induction.

Women with Wilson's disease may have severe oligomenorrhea or amenorrhea whose cause is unknown. The endocrine profile of four such cases was investigated by measuring basal values and the response to dynamic tests of hypothalamic, pituitary, thyroid, and adrenal function, which all proved normal. Ovarian function was disturbed, as witnessed by low estradiol, high total testosterone (T) levels with normal free T, and mildly elevated androstenedione. An interference of ovarian follicular aromatase activity possibly due to copper intoxication could explain these findings as the cause of the ovulatory disturbances of Wilson's disease.

Chlorpromazine (CPZ, Thorazine) administration has been found to result in an increase in peripheral serum levels of prolactin (hPRL) in both men and women. Normal menstruating women were found to have at least a doubling of serum hPRL (100% increase) over basal values within 150minutes of the intramuscular administration of CPZ (0.7mg/kg). Thirty-nine women with oligomenorrhea or amenorrhea with normal or elevated basal levels of serum hPRL were evaluated by this testing modality. Their responses were compared with those of normal women as well as those of 18 women with elevated serum hPRL levels and roentgenographic evidence of pituitary microadenoma. Women with oligomenorrhea or amenorrhea and normal serum hPRL levels generally had a normal response to CPZ (9 of 16 [56.3%]). A smaller percentage of normal responses was found in women with elevated hPRL levels but no overt evidence of pituitary microadenoma (7 of 21 [33%]). Women with elevated hPRL levels and evidence of pituitary microadenoma uniformly failed to have a normal hPRL response following CPZ administration. Although the group with microadenomas did not show a significant hPRL response to CPZ, this test does not unequivocally differentiate between women who have evidence of pituitary adenoma and those who do not. Suggestive, but not conclusive, evidence of hypothalamic dysfunction as the cause of the oligomenorrhea or amenorrhea is presented.

Four women with unexplained infertility and two anovulatory oligomenorrheic women who experienced repeated premature luteinization when treated with human menopausal gonadotropin (hMG) or gonadotropin-releasing hormone (GnRH) were given the gonadotropin-releasing hormone agonist (GnRHa), luprolide acetate, in order to effect medical hypophysectomy. This was followed by hMG for induction of ovulation. Four of the six patients had hMG-only cycles, which were compared with the luprolide acetate/hMG cycles. The luprolide acetate/hMG cycles resulted in normal folliculogenesis with presumptive ovulation. In luprolide/hMG cycles, significantly more hMG was needed for induction of ovulation than in hMG-only cycles. Premature luteinization was abolished with luprolide acetate treatment.

Life-table analysis was performed for the cumulative spontaneous pregnancy rate (CSPR) of 56 patients with oligomenorrhea and anovulatory cycles who had been treated with gonadotropin for ovulation induction between 1963 and 1985. Twenty-seven had at least one spontaneous pregnancy, giving rise to a CSPR of 66.4% (95% confidence limit [CL] 42.4% to 90.4%) at 115 months for the first spontaneous pregnancy, which is significantly lower than the cumulative induced pregnancy rate (CIPR) of 88.6% at 23 months for the first course of gonadotropin therapy (P less than 0.0001). This fertility potential was not affected by the baseline estrogen and follicle-stimulating hormone levels, diagnosis, result of gonadotropin therapy, and age and menstrual pattern during exposure to spontaneous pregnancy by Cox regression analysis. More multiple births occurred in the induced pregnancies than in the spontaneous pregnancies (P = 0.005).

Three hundred seventy-six infertile women in whom there was evidence of ovulatory dysfunction were compared to fertile controls to determine if being excessively under or overweight at the time of planned conception was associated with an increased risk of infertility. In nulligravid women (n = 204), body weight for height 85% or less than "ideal" was associated with a 4.7-fold increase in risk (95% confidence interval = 1.5 to 14.7) of infertility associated with ovulatory dysfunction. Nulligravid women who were 120% or more over their ideal weight were also at increased risk for ovulatory infertility (relative risk = 2.1, 95% confidence interval = 1.0 to 4.3). Neither association was seen among women who had been previously pregnant. The presence of abnormalities of endocrinologic reproductive function in underweight and overweight women argues that the associations we have noted in nulligravid women represent cause-and-effect relationships. If so, we estimate that 6% of primary infertility in which ovulatory dysfunction is present results from being excessively underweight, and another 6% from being excessively overweight.

Eight highly competitive swimmers were followed over a 9-month period during a vigorous training schedule. When compared, four oligomenorrheic (group I, greater than 60 days without menses) and four eumenorrheic (group II) swimmers were not significantly different for age, years of training, body fat, intensity of training, and baseline estradiol (E2) levels. Both groups were challenged during the peak of their training schedule with 10 mg of naloxone and 10 mg of metoclopramide. The naloxone infusion revealed a significant increase in baseline luteinizing hormone (LH) levels in the oligomenorrheic swimmers when compared with the eumenorrheic swimmers. During the metoclopramide infusion prolactin (PRL) increased in all subjects, with a slightly higher increase in PRL in the eumenorrheic swimmers. The study suggests the menstrual dysfunction observed in these strenuously training swimmers to be related to the abnormalities of endorphin physiology as revealed by the elevation in LH after a naloxone infusion.

Hypercarotenemia has been associated with anorexia nervosa and hypothalamic amenorrhea. With the emergence of a spectrum of menstrual dysfunction, including anovulation in women runners, the hypothesis of hypothalamic amenorrhea in these patients has been formulated. Other authors have proposed exercise-associated amenorrhea to be distinct from hypothalamic amenorrhea based on endocrine profiles. Using carotene as an index test of hypothalamic amenorrhea, we have studied female long-distance runners (greater than 25 miles/week) and have found no difference in the carotene levels between ovulatory (midfollicular) and anovulatory runners. These data support other evidence that exercise-associated amenorrhea is distinct from hypothalamic amenorrhea.

Daily plasma hormones, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1), estradiol (E2), progesterone, androstenedione, and testosterone (T), were measured in 16 anovulatory patients for a span of 3 to 4 weeks. The clinical diagnoses in this group of patients included the following: anovulation-eumenorrhea (n = 5), anovulation-polymenorrhea (n = 1), anovulation-oligomenorrhea (n = 3), congenital adrenal hyperplasia (n = 1), polycystic ovarian disease (n = 4), severe hypothalamic amenorrhea (n = 1), and postpartum amenorrhea-galactorrhea (n = 1). Follicular activity was evident in polymenorrheic and oligomenorrheic patients, and menstruation occurred in these patients following estrogen withdrawal. No follicular maturation was noted in the group of patients with anovulation-eumenorrhea, and menstruation in these patients was considered breakthrough bleeding. Low FSH levels were observed in anovulatory patients with eumenorrhea, polymenorrhea, and oligomenorrhea. Significantly high LH values were noted in both classic and non-classic polycystic ovarian disease. Extremely low E1 and E2 levels were found in patients with severe hypothalamic amenorrhea and postpartum amenorrhea-galactorrhea. Slightly elevated progesterone levels were observed in polymenorrheic and oligomenorrheic patients prior to menstruation; this was frequently associated with an LH surge or elevation. Elevated T levels were consistently associated with hirsutism but not with obesity.

Two primary amenorrheic sisters were diagnosed as 46,XX pure gonadal dysgenesis. Their brother, a normal phenotypic and genotypic male, was azoospermic due to primary germinative failure. Parental consanguinity was observed, suggesting an autosomal recessive inheritance. This is the first reported family in which both an otherwise healthy male and two females were affected by gonadal germinative failure. Endocrine studies showed impaired gonadal function in the three affected siblings. The two females with gonadal dysgenesis and the azoospermic male shared one human leukocyte antigen haplotype; the second haplotype, however, was different. The common haplotype was also found in the oligomenorrheic sister whose gonadotropin- releasing hormone test was compatible with normal ovarian function, in the mother, and in one of her offspring who had a normal spermiogram. Hence, linkage between human leukocyte antigens and gonadal failure in this family had been excluded. The possible etiology of familial, chromosomally competent, gonadal failure is discussed.

Gonadotropin levels and secretory patterns were studied in 28 oligomenorrheic patients with various types of polycystic ovary disease (PCO). On the basis of ovarian morphology and histology, the patients PCOuld be separated into two distinct categories arbitarily designated "typical" (type I) and "atypical" (type II) PCO. Although no differences were noted in symptomatology or 17-ketosteroid, testosterone, or follicle-stimulating hormone levels, the 12 type I patients demonstrated widely fluctuating, but markedly elevated, luteinizing hormone (LH) levels, while the 16 type II patients demonstrated lower and less fluctuating LH levels which were comparable to those found during the normal follicular phase. It is likely that type I PCO is a distinct entity similar to that described by Stein and Leventhal, while type II co represents a heterogenous spectrum of disorders, many of which remain obscure.

Serum measurements of bioactive (bio) luteinizing hormone (LH), immunoreactive (i) LH, iLH/follicle-stimulating hormone (FSH) ratios, serum androgens and estradiol (E2) were determined in 20 women with the clinical diagnosis of the polycystic ovary syndrome (PCO), and compared with the levels of 10 women with chronic anovulation (CA) and 10 control subjects in the early follicular phase. Women with CA and control subjects had similar levels of E2, androgens, bioLH, iLH, and iLH/FSH ratios. Fourteen of 20 women with PCO had levels of iLH exceeding 3 standard deviations (SD) of the levels of control women (21 mIU/ml), and 13 of 20 had iLH/FSH ratios above 3.2 (3 SD of control levels). Nineteen of 20 women, however, had bioLH levels above 70 mIU/ml (3 SD of control levels). Mean levels for bioLH were 131 +/- 18 in PCO, 39 +/- 3 in control subjects, and 40 +/- 3 in women with CA. The ratio of bioLH/iLH was 3.5 +/- 0.4 in control subjects and 3.2 +/- 0.3 in women with CA but significantly elevated in PCO (4.6 +/- 0.4, P less than 0.05). There was, however, a significant positive correlation between bioLH and iLH values in PCO (r = 0.64, P less than 0.01). A significant correlation was found between bioLH and serum testosterone as well as between bioLH and serum dehydroepiandrosterone sulfate (DHEA-S) (P less than 0.05), although no correlation was found between iLH and serum DHEA-S. Weight and obesity also did not correlate with either iLH or bioLH in women with PCO and CA. These data suggest that bioLH may be an important hormonal marker in the clinical diagnosis of PCO.

We have found the mean levels of combined serum testosterone and dihydrotestosterone (T+DHT) and the free index (FI) to be significantly higher and the mean dihydrotestosterone precipitation index (DHT-PI) to be significantly lower in hirsute women than in normal women. Although the mean T+DHT values of the different groups of hirsute patients were comparable, the FI value of the oligomenorrheic and/or obese patient was higher than that of the nonobese, normally menstruating group. In addition, the mean DHT-PI level of obese patients was significantly lower than that of nonobese patients. The lowest androgen binding was found in obese patients with oligomenorrhea. In our experience, hirsutism is associated with T+DHT values of 150 ng/dl or lower. Measurement of androgen binding and androgen levels in unchromatographed serum extracts provides valuable information in the treatment of hirsute women.