Gonadotropin for Precocious Puberty Unrelated to Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) in adult women was not increased by gonadotropin releasing hormone analogue (GnRHa) therapy for precocious puberty received as children. These findings, from a retrospective cohort study, were published in Clinical Diabetes and Endocrinology.

Data from children  (N=51) diagnosed with central precocious puberty (CPP) at the Hadassah Ein-Kerem Medical Center in Israel between 1989 and 2011 were included in the study. Long-term outcomes were assessed on the basis of treatment received.

Children received GnRHa (n=27) or no treatment (n=24) and were aged mean 7.3±0.6 and 7.6±0.6 years at diagnosis, had a bone age at diagnosis of 9.6±1.7 and 10.7±1.7 years, and body mass index (BMI) percentile at diagnosis was 80.5%±19.3% and 75.7%±24.9%, respectively. No baseline features differed significantly between cohorts.

Among the GnRHa recipients, treatment was initiated at aged mean age 8.6±1.1 years  with a treatment duration of 24.3±12.8 months. Menarche occurred 10.0±3.5 months after treatment was discontinued.

At an average follow-up time of 10.9±3.8 years (patient age at follow-up ranged from 15.1 to 38.8 years) two patients successfully conceived within six months. One of the women delivered at term and the other had an early spontaneous miscarriage.

Polycystic ovary syndrome was diagnosed among 19.6% at follow up, 22.2% among the treatment groups and 12.5% among the non-treatment groups  (P =.47).

Oligomenorrhea or amenorrhea occurred among 33.3% overall and at a similar rate among GnRHa and those not treated with GnRHa. Hyperandrogenism was reported in 29.6 of women in the treatment group and 29.2 in the untreated group. (P=.97).

The only significant effect associated with GnRHa therapy for precocious puberty was in height, in which the treatment recipients were taller in adulthood (mean, 160.8 cm vs 154.8 cm; P =.026).

In a univariate analysis of PCOS predictors, including age, BMI percentile and clinical signs of puberty at CPP diagnosis, no significant factors associated with increased risk for PCOS in adulthood when compared to the rest of the cohort were found.

This study was limited by a relatively small sample size and lack of hormonal and sonographic data relevant to PCOS diagnosis. In addition, the cohort of patients was relatively young, making a fertility analysis infeasible.

“We did not find any GnRHa treatment-associated difference in frequency of PCOS, two decades and more after the precocious onset of puberty,” the researchers concluded. “This data supports the overall safety of GnRHa therapy with regard to PCOS occurrence.”

Reference

Karavani G, Chill HH, Schachter-Safrai N, Lomnitz G, Gillis D, Bauman D. Gonadotropin releasing hormone analogue treatment of central precocious puberty is not associated with altered prevalence of polycystic ovary syndrome: a single center cohort study. Clin Diabetes Endocrinol. 2021;7(1):14. doi:10.1186/s40842-021-00129-4