Clinical Evidence That Hyperinsulinaemia Independent of Gonadotropins Stimulates Ovarian Growth

Objective: Ovarian enlargement is a constant feature of syndromes of extreme insulin resistance. The objective of this study is to show the role of insulin on ovarian growth in the presence of low gonadotropin levels.

Patients: Seven young patients with syndromes of extreme insulin resistance (five with lipodystrophy, one with Type B syndrome and one with Rabson-Mendenhall syndrome) were studied.

Measurements: Baseline LH concentrations and luteinizing hormone releasing hormone (LHRH) tests were performed. Total testosterone, insulin and C-peptide values were measured. Pelvic ultrasounds were performed.

Results: Four patients were prepubertal (age range 7-10 years old) and had prepubertal gonadotropin levels, and 2 of the 4 who were tested did not respond to LHRH (NIH 10 and RM-PAL). Three patients were Tanner stage 4 (age range 13-17 years old) and had low gonadotropins that did not respond to LHRH stimulation test. All seven patients had marked hyperinsulinaemia and 6 of 7 had at least one enlarged ovary. Testosterone values were increased in 4 of 7 patients.

Conclusion: This represents the first example of the pathologic role of insulin to stimulate ovarian growth with low circulating gonadotropins. Thus, while ovarian growth and steroidogenesis are normally stimulated by gonadotropins at puberty, hyperinsulinaemia stimulates pathologic growth of the ovary and an androgenic steroid profile that is active at all ages. We suggest that these patients constitute a model to separate the effect of insulin from gonadotropin in stimulating ovarian growth and/or steroidogenesis.