A DOPAMINE D-3 RECEPTOR GENOTYPE IS ASSOCIATED WITH HYPERANDROGENIC CHRONIC ANOVULATION AND RESISTANT TO OVULATION INDUCTION WITH CLOMIPHENE CITRATE IN FEMALE HISPANICS

Objective: To determine if dopamine (D-3) receptor genotypes are assoc iated with anovulation and response to ovulation induction with clomip hene citrate. Design: Clinical and laboratory characteristics of anovu latory 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. Interven tions: Genomic DNAs were extracted from each patient. Polymerase chain reaction with subsequent restriction digest was performed to analyze the D-3 receptor allele status (two possible alleles). Main Outcome Me asures: Menstrual history, serum T, and midluteal serum Ps from sponta neous and clomiphene cycles were correlated with D-3 receptor genotype .Results: Hispanic females with the 22 genotype compared with the othe r genotypes (11 and 12) were more likely to have irregular menses, an elevated serum T (greater than or equal to 70 ng/dL [conversion factor to SI unit, 3.467]), and hyperandrogenic chronic anovulation. These p atients tended to be resistant to ovulation induction requiring a sign ificantly 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 patien t age, weight, or serum T level. Conclusions: Hyperandrogenic chronic anovulation may have a genetic component. Genetic analysis may be usef ul in predicting resistance to ovulation induction with clomiphene.