Menstrual disorders and infertility caused by inactivating mutations of the luteinizing hormone receptor gene

OBJECTIVE: To review clinical findings, hormone levels, and DNA analyses in genetic males and females with inactivating mutations of the LH receptor gene. DESIGN: Review of reported cases. SETTING: A university hospital. PATIENT(S): Genetic males and females with inactivating mutations of the LH receptor gene. RESULT(S): The clinical presentation in genetic males ranged from female genitalia to male genitalia with micropenis caused by Leydig cell hypoplasia. Genetic females presented with amenorrhea or oligomenorrhea, enlarged cystic ovaries, and infertility. Both males and females had elevated LH levels and LH/FSH ratios. Sequencing of genomic DNA revealed homozygous or compound heterozygous deletions, nonsense mutations, or missense mutations in the LH receptor gene. CONCLUSION(S): This study of patients with inactivating mutations of the LH receptor indicates that in genetic males, the action of hCG and LH is necessary for the normal development of primary and secondary sexual characteristics. In contrast, secondary sexual characteristics develop in genetic females in the absence of LH action, but they fail to ovulate.