Objective: To evaluate the clinical significance of the LH consisting of a mutant beta-subunit (Trp8 to Arg8 and Ile15 to Thr15).
Design: Clinical and biochemical studies.
Setting: Fertility center at the University Hospital and its research laboratory.
Patients: Fifty-one patients with menstrual disorders and three homozygote cases and two heterozygote cases of the mutant LH who were reported previously.
Interventions: Nucleotide mutations of the LH beta gene in patients with menstrual disorders were screened using techniques of the polymerase chain reaction and restriction fragment length polymorphism. Immunologic and biologic activities of the mutant LH and endocrinologic profiles in the affected women were evaluated.
Main outcome measures: Serum LH levels measured with different immunoassay kits; serum FSH and LH on the GnRH test; serum thyroid-stimulating hormone, PRL, T, and androstenedione; ultrasound examination of the ovaries; clinical hyperandrogenic symptoms; and biologic activity of LH.
Results: Two cases of homozygotes and four of heterozygotes affected by the LH beta gene mutations were discovered in the current study through screening of patients with menstrual disorders. Serum LH levels in the homozygote cases were undetectable using a LH immunoassay kit, whereas levels in the heterozygote cases showed reduced detectability with the kit. However, the ratio of the mutant LH values in the bioassay to those in the immunoassay was higher in the homozygote group than that in the control subjects. Response patterns of serum gonadotropins to GnRH in the homozygote were similar to those in patients with polycystic ovary syndrome.
Conclusion: The mutations of LH beta-subunit might be related to menstrual disorder in some patients.