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 g ene. 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 ge nitalia to male genitalia with micropenis caused by Leydig cell hypoplasia. Genetic females presented with amenorrhea or oligomenonrrhea, enlarged cys tic ovaries, and infertility. Both males and females had elevated LH levels and LH/FSH ratios. Sequencing of genomic DNA revealed homozygous or compou nd 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 nece ssary for the normal development of primary and secondary sexual characteri stics. In contrast, secondary sexual characteristics develop in genetic fem ales in the absence of LH action, but they fail to ovulate. (Fertil Steril( R) 1999;71:597-601. (C)1999 by American Society for Reproductive Medicine.) .