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 (≥ 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.