Hypogonadism in Prader–Willi syndrome from birth to adulthood: a 28-year experience in a single centre

Abstract

Background: Hypogonadism is a key feature of Prader–Willi syndrome (PWS) but clear strategies for hormone replacement are lacking. Objective: To evaluate the gonadal status and outcome in patients attending a Scottish PWS clinic from 1991 to 2019. Methods: In 93 (35F:56M) patients, median follow-up 11.2 years, gonadal and pubertal status were assessed clinically. Pelvic ultrasound findings and basal/stimulated gonadotrophins were compared with age-matched controls. Results: Females: of 22 patients aged > 11, 9 had reached B4–5, while 5 were still at B2–3, and 6 remained prepubertal. Eight patients experienced menarche aged 9.8–21.4 years, none with a normal cycle. Uterine length and ovarian volumes were normal but uterine configuration remained immature, with low follicular cou nts. Gonadotrophins were unremarkable, serum oestradiol 129 (70–520) pmol/L. Only 5 patients received oestrogen replacement. Males: fifty-four (96%) patients were cryptorchid (9 unilateral). Weekly hCG injections resulted in unilateral/bilateral descent in 2/1 of 25 patients. Of 37 boys aged > 11, 14 (9 with failed/untreated bilateral cryptorch idism) failed to progress beyond G1, 15 arrested at G2–3 (testes 3–10 mL), and 8 reached G4–5. Gonadotrophins were unremarkable except in boys at G2–5 in whom FSH was elevat ed: 12.3/27.3 vs 3.25/6.26 U/L in controls (P 13, testosterone was 3.1 (0.5–8.4) nmol/L. Androgen therapy, given from 13.5 to 29.2 years, was st opped in 4/24 patients owing to behavioural problems. Conclusion: Despite invariable hypogonadism, few females and only half the males with PWS in this study received hormone replacement. Double-blind placebo-controlled crossover trials of sex steroids are required to address unproven behavioural concerns.

Keywords

• prader–willi syndrome
• central hypogonadism
• primary hypogonadism
• cryptorchidism
• orchidopexy
• pelvic ultrasound
• gonadotrophins
• human chorionic gonadotrophin
• puberty
• oestrogen therapy
• testosterone therapy