GNRH analog therapy in girls with early puberty is associated with the achievement of predicted final height but also with increased risk of polycystic ovary syndrome

Abstract

Objective: GNRH analog (GNRHa) therapy has not been supported by beneficial effects on adult stature in girls with early puberty. Furthermore, an increased prevalence of polycystic ovary syndrome (PCOS) has been described in girls treated for central precocious puberty. Women with PCOS are at increased risk of cardiometabolic dysfunctions and infertility. Our aim was to assess GNRHa effectiveness on reaching adult stature and the risk of PCOS in girls with early puberty. Design: Longitudinal study of GNRHa-treated and GNRHa-untreated girls at baseline and at final height. Methods: Twenty-five GNRHa-treated girls and 55 controls were compared. Insulin resistance (IR; homeostasis model assessment of IR (HOMA-IR) and glucose-to-insulin ratio (G/I)), the effect of GNRHa on final height, and the prevalence of PCOS were assessed. Results: In GNRHa-treated girls, no significant difference was found between predicted final height and final height, whereas a significant difference was detected in untreated girls (PZ0.0001). At final height, GNRHa-treated girls showed higher HOMA-IR and lower G/I (PZ0.03 for both) as well as higher DHEAS and androstenedione levels (PZ0.02 and PZ0.01 respectively) than untreated girls. The prevalence of PCOS and hyperandrogenemia was significantly higher in GNRHa-treated adolescents than in untreated adolescents (36 and 14.5% respectively, PZ0.04; 56 and 23.6% respectively, PZ0.01). Finally, gonadotropin-suppressive therapy was significantly related to PCOS during adolescence (PZ0.03). Conclusions: In girls with early puberty, GNRHa therapy is associated with the achievement of predicted final height; nevertheless, this treatment seems to act as an independent risk factor for the development of PCOS already during adolescence.

Metabolic Outcomes, Bone Health, and Risk of Polycystic Ovary Syndrome in Girls with Idiopathic Central Precocious Puberty Treated with Gonadotropin-Releasing Hormone Analogues

“…Our results demonstrated that neither CPP nor GnRHa therapy influence BMI 2 or more years after menarche. Moreover, we found no differences for lipid profile, fasting glucose, or fasting insulin between the 2 groups, but a significantly greater HOMA-IR in the GnRHa-treated patients, confirming previous data [48, 49]. …”

Bilateral Oophorectomy and the Risk of Incident Diabetes in Postmenopausal Women

“…Since women who have undergone BSO have lower androgen levels than women with intact ovaries, we began this study with the hypothesis that BSO would reduce diabetes risk. Correction of androgenicity among women with polycystic ovary syndrome by laparoscopic ovarian cautery did not improve insulin sensitivity (32), and reduction in ovarian sex steroid production by gonadotropin-releasing hormone analogs in girls with early puberty increased insulin resistance later in life (33). Thus, ovarian androgens are unlikely to explain our results.…”

The Influence of GnRH Analog Therapy on Growth in Central Precocious Puberty

“…Chiavaroli et al analyzed the effect of GnRHa therapy on adult height in girls with early puberty (onset between the ages of 8 to 10) and found that the treatment had no positive impact on the girls' final height. Additionally, they noted that girls with early puberty have an increased risk of polycystic ovarian syndrome [16].…”