Is There a Difference in Hirsutism Score in Adolescents with Polycystic Ovary Syndrome on the Basis of Ethnicity and Race?

BACKGROUND: The complex correlation between ethnicity and race, clinical hyperandrogenism as signified by hirsutism, and biochemical androgen concentrations in polycystic ovary syndrome (PCOS) is poorly understood. STUDY OBJECTIVE: The aim of this study was to define the correlation between ethnicity/race and hirsutism score in patients with PCOS. METHODS: We conducted a retrospective chart review of a total of 251 patients with PCOS at the time of diagnosis. Patients were categorized by their ethnicity and race into 5 main groups: Asian (n = 19, 7.6%), Black or African American (n = 11, 4.4%), Hispanic or Latino (n = 26, 10.3%), White (n = 177, 70.5), and others (n = 18, 7.2%). A general linear model was applied using BlueSky software. RESULTS: For the entire study population, the mean age at diagnosis was 15.6 ± 1.7, the mean body mass index (BMI) was 30.6 ± 9.8, the mean hirsutism score using the modified Ferriman-Gallwey score chart was 6.2 ± 3.8, and the mean total testosterone was 40.1 ± 20. The hirsutism score was the highest in the Asian population (mean = 9.1, P = .002) and Hispanic or Latino population (mean = 7.8, P = .02), followed by others (mean = 7.4, P = .04) and the Black or African American population (mean = 7.1, P = .2), compared with the White population (mean = 5.4). This correlation remained significant despite accounting for BMI and androgen levels (P < .001). CONCLUSION: There are factors likely related to hair follicle sensitivity or endogenous response to circulating free androgens that differ between ethnicities and races, such that similar biochemical concentrations lead to differing severity of hirsutism, despite accounting for differences in BMI and androgen levels. More research is needed in this realm to understand the pathophysiologic basis of this interaction.

Influence of ethnicity on different aspects of polycystic ovary syndrome: a systematic review.

This systematic review aimed to assess variations in the clinical presentation and treatment outcomes of patients with polycystic ovary syndrome (PCOS) belonging to different ethnicities. A search was performed for studies comparing various clinical aspects of PCOS in two or more different ethnic groups. After screening 2264 studies, 35 articles were included in the final analysis. In comparison with White women with PCOS (wPCOS), East Asian women with PCOS (eaPCOS) were less hirsute, whereas Hispanic women with PCOS (hPCOS), South Asian women with PCOS (saPCOS) and Middle Eastern women with PCOS (mePCOS) were more hirsute. saPCOS had higher androgen and lower sex hormone-binding globulin (SHBG) concentrations, mePCOS had higher DHEAS concentrations, and hPCOS and Black women with PCOS (bPCOS) had lower SHBG and DHEAS measures than wPCOS. Menstrual disturbances were more frequent in eaPCOS. Both saPCOS and eaPCOS had lower body mass index with increased central adiposity. hPCOS and bPCOS were more obese. saPCOS, mePCOS, hPCOS and bPCOS had a higher prevalence of insulin resistance than wPCOS. bPCOS had a better lipid profile but higher blood pressure and cardiovascular risk. Indigenous Australian women with PCOS were more obese and more insulin resistant with higher androgen concentrations. The clinical phenotype of PCOS therefore shows a wide variation depending on ethnicity.

Phenotype and genotype of polycystic ovary syndrome in Asia: Ethnic differences.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women, and ethnic diversity has been reported in its manifestation. This review addressed phenotype and genetic studies in Asian women with PCOS. Generally, East Asians are less hirsute, and the hirsutism score cutoff is lower than the Caucasian counterpart. It is not clear whether there are any significant differences in the prevalence or severity of irregular menstruation (IM) or characteristics of polycystic ovary (PCO) across ethnicities. Interestingly, the IM/PCO subgroup is a relatively common phenotype in East Asian patients but not in Caucasian patients. The prevalence of insulin resistance in PCOS patients varies depending on the index used and the cutoff, but women with PCOS showed a higher degree of insulin resistance than those of controls across ethnicities. Lower body mass index (BMI) and lower prevalence of metabolic syndrome were reported in East Asian patients, but despite lower BMI, a comparative study reported that Asian women with PCOS were more likely to have diabetes compared with Caucasian patients, suggesting they also have metabolic complications. Unlike East Asian patients, South Asian patients showed an increased degree of hirsutism, early onset of symptoms, and severe insulin resistance and metabolic risks compared with Caucasians. Genetic components play important roles in the pathogenesis of PCOS, and genome-wide association studies of PCOS suggest that similar genetic risk factors exist between Asian and Caucasian patients. Continuous comparative studies are needed to standardize the diagnosis and management of PCOS across different ethnicities.

Racial and ethnic differences in the polycystic ovary syndrome metabolic phenotype.

BACKGROUND: Women with polycystic ovarian syndrome have a high prevalence of metabolic syndrome and type 2 diabetes mellitus. Blacks and Hispanics have a high morbidity and mortality due to cardiovascular disease and diabetes mellitus in the general population. Since metabolic syndrome is a risk factor for development of type 2 diabetes and cardiovascular disease, understanding any racial and ethnic differences in metabolic syndrome among women with polycystic ovarian syndrome is important for prevention strategies. However, data regarding racial/ethnic differences in metabolic phenotype among women with polycystic ovary syndrome are inconsistent. OBJECTIVE: We sought to determine if there are racial/ethnic differences in insulin resistance, metabolic syndrome, and hyperandrogenemia in women with polycystic ovarian syndrome. STUDY DESIGN: We conducted secondary data analysis of a prospective multicenter, double-blind controlled clinical trial, the Pregnancy in Polycystic Ovary Syndrome II study, conducted in 11 academic health centers. Data on 702 women with polycystic ovarian syndrome aged 18-40 years who met modified Rotterdam criteria for the syndrome and wished to conceive were included in the study. Women were grouped into racial/ethnic categories: non-Hispanic whites, non-Hispanic blacks, and Hispanic. The main outcomes were the prevalence of insulin resistance, metabolic syndrome, and hyperandrogenemia in the different racial/ethnic groups. RESULTS: Body mass index (35.1 ± 9.8 vs 35.7 ± 7.9 vs 36.4 ± 7.9 kg/m2) and waist circumference (106.5 ± 21.6 vs 104.9 ± 16.4 vs 108.7 ± 7.3 cm) did not differ significantly between non-Hispanic white, non-Hispanic black, and Hispanic women. Hispanic women with polycystic ovarian syndrome had a significantly higher prevalence of hirsutism (93.8% vs 86.8%), abnormal free androgen index (75.8% vs 56.5%), abnormal homeostasis model assessment (52.3% vs 38.4%), and hyperglycemia (14.8% vs 6.5%), as well as lower sex hormone binding globulin compared to non-Hispanic whites. Non-Hispanic black women had a significantly lower prevalence of metabolic syndrome (24.5% vs 42.2%) compared with Hispanic women, and lower serum triglyceride levels compared to both Hispanics and non-Hispanic whites (85.7 ± 37.3 vs 130.2 ± 57.0 vs 120.1 ± 60.5 mg/dL, P < .01), with a markedly lower prevalence of hypertriglyceridemia (5.1% vs 28.3% vs 30.5%, P < .01) compared to the other 2 groups. CONCLUSION: Hispanic women with polycystic ovarian syndrome have the most severe phenotype, both in terms of hyperandrogenism and metabolic criteria. Non-Hispanic black women have an overall milder polycystic ovarian syndrome phenotype than Hispanics and in some respects, than non-Hispanic white women.

Adrenal Hyperandrogenism and Polycystic Ovary Syndrome.

BACKGROUND: The prevalence of adrenal hyperandrogenism (AH), as defined by increased circulating dehydroepiandrosterone-sulfate (DHEAS) levels, ranges from 15 to 45% in women with polycystic ovary syndrome (PCOS). METHODS: The aim of this review is to update the pathogenesis and consequences of AH in PCOS, from molecular genetics to the clinical setting. RESULTS: Mounting evidence derived from animal models suggests that genetically or enviromentally determined prenatal androgen excess, by influencing the hormonal and metabolic phenotype of susceptible female fetuses later in life, may be the capital event for the development of AH in PCOS. Because human placental aromatase activity is likely to prevent any deleterious effect of maternal hyperandrogenemia on the fetus, inheritance of the maternal steroidogenic defect is the more likely culprit, even though other factors such as changes in placental steroidogenesis itself or its nutritional efflux may also be involved in the building a deregulated enzymatic pathway from utero to adult life. Anyhow, the most important issue is whether or not AH influences the cardiometabolic risk of women with PCOS. On the one hand, AH has shown a controversial relationship with carbohydrate metabolism and adiposity, and is also associated with abnormalities in blood pressure regulation in these patients. On the other hand, DHEAS may exert a beneficial effect on the lipid profile of both lean and obese patients. Lastly, available studies in women with PCOS cast doubt upon a protective role of DHEAS levels on subclinical atherosclerosis, despite opposite data from the general population. CONCLUSION: AH is frequent in patients with PCOS yet unraveling its consequences for the management of this disorder requires future longitudinal studies.

Ethnic differences: Is there an Asian phenotype for polycystic ovarian syndrome?

Ethnicity has not been accounted for in the diagnostic criteria for polycystic ovarian syndrome (PCOS). It is increasingly recognised that ethnic differences are likely contributors to the differing manifestations of PCOS. Generally, rates of PCOS may be lower in East Asians. It is clear that East Asians are less hirsute than Caucasians. Hirsutism cut-off thresholds need to be lower in East Asian populations than in Caucasian populations. Despite population-adjusted scoring, Caucasians have higher hirsutism rates among patients diagnosed with PCOS. Rates of hyperandrogenaemia do not appear to differ among PCOS subjects, although serum androstenedione appeared to be higher in Caucasians in one study. Interestingly, higher prevalence of the polycystic ovarian morphology has been reported in East Asian PCOS populations than in Caucasian PCOS subjects. Hence, there is a need for comparative studies across different ethnicities to establish whether epidemiological differences observed reflect a true ethnic difference in the phenotype of PCOS and whether there is an Asian phenotype for PCOS.

Observation of phenotypic variation among Indian women with polycystic ovary syndrome (PCOS) from Delhi and Srinagar.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder that demonstrates ethnic and regional differences. To assess the phenotypic variability among Indian PCOS women, we evaluated clinical, biochemical and hormonal parameters of these women being followed in two tertiary care institutions located in Delhi and Srinagar. A total of 299 (210 PCOS diagnosed by Rotterdam 2003 criteria and 89 healthy) women underwent estimation of T4, TSH, LH, FSH, total testosterone, prolactin, cortisol, 17OHP, and lipid profile, in addition to post OGTT, C-peptide, insulin, and glucose measurements. Among women with PCOS, mean age, age of menarche, height, systolic, diastolic blood pressure, and serum LH were comparable. PCOS women from Delhi had significantly higher BMI (26.99 ± 5.38 versus 24.77 ± 4.32 kg/m(2); P = 0.01), glucose intolerance (36 versus 10%), insulin resistance as measured by HOMA-IR (4.20 ± 3.39 versus 3.01 ± 2.6; P = 0.006) and QUICKI (0.140 ± 0.013 versus 0.147 ± 0.015; P = 0.03) while PCOS from Srinagar had higher FG score (12.12 ± 3.91 versus 10.32 ± 2.22; P = 0.01) and serum total testosterone levels (0.65 ± 0.69 versus 0.86 ± 0.41 ng/ml; P = 0.01. Two clear phenotypes, i.e. obese hyperinsulinaemic dysglycemic women from Delhi and lean hyperandrogenic women from Srinagar are emerging. This is the first report on North Indian women with PCOS showing phenotypic differences in clinical, biochemical and hormonal parameters despite being in the same region.

Characteristics and contributions of hyperandrogenism to insulin resistance and other metabolic profiles in polycystic ovary syndrome.

OBJECTIVE: To investigate the different characteristics in Chinese Han women with polycystic ovary syndrome, and to analyze the significance of hyperandrogenism in insulin resistance and other metabolic profiles. DESIGN: A cross-sectional study. SETTING: Medical university hospital. POPULATION: A total of 229 women with polycystic ovary syndrome aged 18-45 years. METHODS: Women with polycystic ovary syndrome, diagnosed by Rotterdam criteria, were divided into four groups according to the quartile intervals of free androgen index levels. MAIN OUTCOME MEASURES: Comparisons between groups were performed using one-way analysis of variance. Stepwise logistic regression analysis was performed to investigate the association between homeostasis model assessment-insulin resistance and independent variables. RESULTS: Within the four phenotypes, women with phenotype 1 (hyperandrogenism, oligo/anovulation, and polycystic ovaries) exhibited higher total testosterone, free androgen index, androstenedione, low-density lipoprotein, and lower quantitative insulin sensitivity check index (p < 0.05); women with phenotype 4 (oligo/anovulation and polycystic ovaries) showed lower total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance, but higher high-density lipoprotein (p < 0.05). The levels of triglycerides, total cholesterol, low-density lipoprotein, and homeostasis model assessment-insulin resistance significantly increased, but high-density lipoprotein and quantitative insulin sensitivity check index decreased with the elevation of free androgen index intervals. After adjustment for lipid profiles, free androgen index was significantly associated with homeostasis model assessment-insulin resistance in both lean and overweight/obese women (odds ratio 1.302, p = 0.039 in lean vs. odds ratio 1.132, p = 0.036 in overweight/obese). CONCLUSIONS: Phenotypes 1 and 4 represent groups with the most and least severe metabolic profiles, respectively. Hyperandrogenism, particularly with elevated free androgen index, is likely a key contributing factor for insulin resistance and for the aggravation of other metabolic profiles.

Phenotypic comparison of Caucasian and Asian women with polycystic ovary syndrome: a cross-sectional study.

OBJECTIVE: To determine whether manifestations of polycystic ovary syndrome (PCOS), particularly androgen excess, differ between Caucasian and Asian women in the San Francisco Bay Area. DESIGN: Cross-sectional study. SETTING: Multidisciplinary PCOS clinic at a tertiary academic center. PATIENT(S): 121 Caucasian and 28 Asian women, aged 18-44, examined between 2006 and 2011 with PCOS verified by a reproductive endocrinologist and dermatologist according to the Rotterdam criteria. INTERVENTION(S): Transvaginal ultrasounds, comprehensive dermatologic exams, and serum testing. MAIN OUTCOME MEASURE(S): Hirsutism defined as a modified Ferriman-Gallwey (mFG) score ≥ 8, acne, androgenic alopecia, and biochemical hyperandrogenism. RESULT(S): Caucasian and Asian women had a similar prevalence of all measures of androgen excess. Both groups had similar total mFG scores and site-specific mFG scores, except Asian women had a lower site-specific mFG score for the chest. Although Asian women were more likely to use laser hair removal, the results were unchanged when the women with a history of laser hair removal were excluded. CONCLUSION(S): Caucasian and Asian women with PCOS living in the same geographic region had a similar prevalence of hirsutism as well as other markers for androgen excess. Further studies are necessary to evaluate the need for ethnic-specific mFG scores in women with PCOS.

Clinical characteristics, metabolic features, and phenotype of Chinese women with polycystic ovary syndrome: a large-scale case-control study.

AIM: The Rotterdam criteria extend the phenotypic spectrum of polycystic ovary syndrome (PCOS). The study was to investigate the clinical and biochemical features of a large-scale clinic based on the samples of Chinese women and to evaluate the value of Rotterdam criteria on Chinese PCOS women. METHODS: One thousand four hundred and four Chinese women were involved in our study, among whom, 719 cases were diagnosed as PCOS based on 2003 Rotterdam criteria, and 685 women without history of hyperandrogenism and with regular menstrual cycles were recruited as control. Clinical features, ultrasonographic (ovarian follicle number and volume), hormonal and metabolic parameters were commenced as outcome measures. RESULTS: Among 719 PCOS women, 6.1 % had hirsutism, 13.3 % had acne, 21.1 % had hyperandrogenism, 94.2 % had polycystic ovaries on ultrasonographic examination, and 88.6 % had menstrual abnormality. About one-third of the total PCOS patients were insulin resistant. The most frequent PCOS phenotype is the non-hyperandrogenic phenotype (O + P). Total testosterone, LH/FSH ratio, body mass index (BMI), and Ferriman and Gallwey scores (F-G) were all significantly higher in PCOS groups compared with non-PCOS group. Women with PCOS and obesity had higher serum testosterone, fasting insulin, longer menstrual cycle and larger ovarian follicle number, and LH/FSH ratio, estradiol or ovarian volume were similar between obese and normal BMI women. The LH level was statistically lower in the obese PCOS group. CONCLUSIONS: Rotterdam criteria are generally applicable to Chinese population. Chinese women with PCOS showed lower rates of hyperandrogenemia, hirsutism, obesity, and insulin resistance. Obesity aggravates menstrual irregularity and increases the follicle number and serum total testosterone level.

The reproductive and metabolic effect of rosiglitazone on Chinese women with polycystic ovarian syndrome--a double-blind randomized placebo-controlled study.

OBJECTIVE: To investigate whether an insulin sensitizer has any effect on amenorrhea and clinical and biochemical hyperandrogenism in Chinese women with polycystic ovarian syndrome (PCOS). DESIGN: Randomized controlled double-blind trial. SETTING: A tertiary referral center, Hong Kong. PATIENT(S): Chinese women who fulfilled the Rotterdam criteria of PCOS (n = 70). INTERVENTION(S): Rosiglitazone 4 mg daily for the first month followed by 4 mg twice daily for 11 months. MAIN OUTCOME MEASURE(S): Menstrual status as well as clinical and biochemical hyperandrogenism. RESULT(S): There is a significantly higher rate of regular menses among the treatment arm (16 [50.0%] of 32 vs 4 [11.8%] of 34) at 6 months and the improvement appeared to be sustained (10 [41.7%] of 24 vs 6 [20.0%] of 30) at 12 months. There was no change in the acne and hirsutism scores as well as serum T levels in both arms. CONCLUSION(S): We found a possible benefit in menstrual cyclicity but a lack of improvement in hyperandrogenism in our Chinese population. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR-TRC-09000670 (Chinese Clinical Trial Registry).

Prominent role of low HDL-cholesterol in explaining the high prevalence of the metabolic syndrome in polycystic ovary syndrome.

BACKGROUND AND AIMS: The main objective was to evaluate the prevalence of the metabolic syndrome in Caucasian women with PCOS, using either of the currently proposed definitions (NCEP/ATPIII, IDF and AHA/NHLBI) and, therefore, to estimate the concordance between these three classifications. Secondary objectives were to evaluate: i) which individual criterion of the metabolic syndrome is most strongly associated with PCOS; and ii) whether the severity of hyperandrogenemia, hyperinsulinemia and insulin resistance may influence the presence of the metabolic syndrome in PCOS women. METHODS AND RESULTS: The metabolic syndrome was assessed in 200 Caucasian women with PCOS and in 200 Caucasian controls, matched for age and BMI, considering the NCEP/ATPIII, IDF and AHA/NHLBI definitions. PCOS women had an increased prevalence of the metabolic syndrome compared with controls: 32 versus 23% with the NCEP/ATPIII, 39 versus 25% with the IDF and 37 versus 24% with the AHA/NHLBI, respectively (Cohen's Kappa index between the three classifications, P < 0.001). Multivariate logistic regressions revealed that among the individual criteria of the metabolic syndrome, only low HDL-cholesterol levels were significantly associated with PCOS (P < 0.001) which, in turn, are related to insulin(AUC) (P = 0.029) but not to androgens. CONCLUSION: This case-control study indicates a high prevalence of the metabolic syndrome in Caucasian PCOS women that is independent of the diagnostic classification used. Furthermore, it shows that low HDL-cholesterol is the criterion which best explains the high prevalence of the metabolic syndrome in PCOS subjects which, in turn, is influenced by hyperinsulinemia, rather than by hyperandrogenemia.

Higher metabolic risk in Chinese women fulfilling the NIH diagnostic criteria for polycystic ovarian syndrome.

Only about 63% of Chinese women with polycystic ovarian syndrome (PCOS) as diagnosed by the 2003 Rotterdam criteria fulfilled the 1990 National Institutes of Health (NIH) diagnostic criteria. Although the NIH criteria are not generally applicable to the Chinese population, women fulfilling the NIH criteria have higher metabolic risk than those who do not and so carry the most clinical significance.

Body shape and size and insulin resistance as early clinical predictors of hyperandrogenic anovulation in ethnic minority adolescent girls.

PURPOSE: To determine whether key associated features of hyperandrogenic anovulation (HA) in predominately Caribbean Hispanic (CH) adolescent girls can be combined to improve the early diagnosis of HA. METHODS: Unselected observational sample of females aged 12 to 21 years (mean 17.5 +/- 2.4 years), (64% CH, 28% African American). One hundred twenty subjects provided a menstrual history, had a physical examination, and a follicular phase fasting blood drawn for LH, FSH, testosterone, sex hormone binding globulin (SHBG), 17-OH progesterone (17-OHP), androstenedione (Delta(4)A), glucose, and insulin. We prospectively categorized subjects into four groups: G I (n = 42) had normal menses and normal physical exam; G II (n = 41) had normal menses and abnormal physical exam, that is, signs indicating possible hyperandrogenism and/or insulin resistance, including at least one of obesity, hirsutism, acne, or acanthosis nigricans; G III (n = 15) had abnormal menses and normal physical exam, and G IV (n = 22) had HA with BOTH abnormal menses and abnormal physical exam, that is, girls most likely to develop polycystic ovary syndrome. Hormonal levels and additional clinical and physical characteristics of interest were compared among the four groups. RESULTS: Group IV subjects had significantly higher waist circumference measurements, independent of overweight status, than all other groups. As hypothesized, Group IV subjects had significantly higher androgen levels and significantly lower SHBG levels than all other groups. FAI, SHBG, and waist circumference had the highest diagnostic accuracy for predicting Group IV status (i.e., HA phenotype). CONCLUSIONS: Markers of insulin resistance and hyperandrogenemia, including waist circumference, FAI, and SHBG, best associate with irregular menstrual cycles and the HA phenotype in ethnic minority adolescent girls.

Clinical and metabolic findings in adolescent females with hyperandrogenism.

BACKGROUND: The purpose of this study was to characterize the population of adolescent females with laboratory evidence of hyperandrogenism and to explore clinical and laboratory features that may facilitate the diagnosis and management of this condition. We further investigated these characteristics by race, weight, and type of androgen abnormality. METHODS: A 4-year retrospective chart review was undertaken. Female patients were included if they attended Adolescent Medicine Clinic and had at least one abnormal laboratory parameter on a testing panel that included total and free testosterone, calculated percent free testosterone, and sex hormone binding globulin levels. RESULTS: Our final sample included 154 females, 70% of whom were white, 28% African-American and 2% of other ethnicities. The mean age was 16.1 years (range 11-23). The mean body mass index (BMI) was 30.4, ranging from 16.6 to 45.0, and 78% were obese (BMI>95th percentile for age). Initial reason for visit included irregular menses in 75.3%, acne or hirsutism in 7.1%, and other reason in 17.5%. Non-whites were more likely than whites to present with other reason for visit (28 vs. 13%, P<0.05). Non-white patients had a higher chronologic and gynecologic age at presentation than whites. Total testosterone was elevated in 82.6% of the non-white compared to 62.0% of the white patient group (P<0.05). There was no difference in BMI or obesity between whites and non-whites. The subgroup of adolescents with an isolated elevated testosterone was leaner, had a younger gynecologic age, and was more likely to have an abnormal glucose to insulin ratio than were those girls with other androgen abnormalities. Of those tested for other metabolic abnormalities, 55% had at least one abnormal lipid value, and 68% had an abnormal glucose to insulin ratio. CONCLUSIONS: Adolescent females with hyperandrogenism are at risk for other metabolic abnormalities. The higher gynecologic age and higher testosterone levels in our non-white patient group may reflect a delay in referral. Primary care physicians need to be sensitive to signs and symptoms of hyperandrogenism in the non-white population and in lean adolescents.

A dopamine D3 receptor genotype is associated with hyperandrogenic chronic anovulation and resistant to ovulation induction with clomiphene citrate in female Hispanics.

OBJECTIVE: To determine if dopamine (D3) receptor genotypes are associated with anovulation and response to ovulation induction with clomiphene citrate. DESIGN: Clinical and laboratory characteristics of anovulatory patients and ovulatory controls were compared with findings at the DNA level. SETTING: An outpatient clinic at an university medical center. PATIENTS: One hundred eighty human Hispanic female volunteers (130 of these with documented ovulatory status) were studied. INTERVENTIONS: Genomic DNAs were extracted from each patient. Polymerase chain reaction with subsequent restriction digest was performed to analyze the D3 receptor allele status (two possible alleles). MAIN OUTCOME MEASURES: Menstrual history, serum T, and midluteal serum Ps from spontaneous and clomiphene cycles were correlated with D3 receptor genotype. RESULTS: Hispanic females with the 22 genotype compared with the other genotypes (11 and 12) were more likely to have irregular menses, an elevated serum T (> or = 70 ng/dL [conversion factor to SI unit, 3.467]), and hyperandrogenic chronic anovulation. These patients tended to be resistant to ovulation induction requiring a significantly higher dose of clomiphene to achieve an ovulatory response (22 genotype [mean +/- SEM] [140.0 +/- 19.0 mg] versus 11 [77.1 +/- 17.5 mg] or 12 [69.2 +/- 13.1 mg]). This effect was independent of patient age, weight, or serum T level. CONCLUSIONS: Hyperandrogenic chronic anovulation may have a genetic component. Genetic analysis may be useful in predicting resistance to ovulation induction with clomiphene.