Hypogonadism and pubertal development in Prader-Willi syndrome

Abstract

Genital abnormalities and disorders of pubertal development such as hypogonadism are common in Prader-Willi Syndrome (PWS). Depending on age, PWS patients present genital hypoplasia and delayed or incomplete gonadal maturation. Nevertheless, only a few evaluations have been made of these findings in this syndrome; in the cases previously reported the diagnosis of PWS has often been based only on clinical criteria and not confirmed by genetic analysis. In this paper we describe both external genital findings and spontaneous pubertal development in 84 patients aged from 2.1 to 35.4 (42 males, 42 females) affected by PWS. Diagnosis was made using the Holm and Cassidy criteria and was confirmed by genetic analysis (methylation test and/or FISH). We evaluated the presence of cryptorchidism, scrotal development, length of penis and volume of testis in males and outlook of labia minora and/or clitoris, age of menarche and features of menses (when present) in females; in both sexes we also evaluated the onset of puberty. All recruited males showed cryptorchidism, which was bilateral in 36 out of 42 patients (86%); 38 patients (90%) underwent orchidopexy. Small testes and scrotal hypoplasia were present in 76% and 69% of cases, respectively. In 76% of females, hypoplasia or absence of labia minora and/or clitoris was described. Spontaneous menarche occurred only in 14/32 cases (44%) over the age of 15 years, but menstrual cycles were often a periodical vaginal spotting. Primary amenorrhea was diagnosed in 56% of cases. Isolated premature pubarche was present in six males and in six females (14% of cases) while one male and two females were affected by precocious puberty (3.6%). Conclusion: Hypogonadism represents a common clinical feature in PWS, confirming the importance of such a major diagnostic criterion. Cryptorchidism was consistently present in all our cases. Patients with PWS commonly fail to spontaneously complete puberty, although some patients may have early pubarche or, more rarely, precocious puberty. In older subjects, hormonal replacement therapy is not always necessary and it must be reserved for selected patients.

Prader-Willi Syndrome: Clinical Aspects

“…In males, the penis may be small; more characteristic is a hypoplastic scrotum that is small, poorly rugated, and poorly pigmented. Unilateral or bilateral cryptorchidism is present in 80–90% of males [35, 36]. In females, genital hypoplasia is often overlooked; however, the clitoris and labia, especially the labia minora, are generally small from birth.…”

“…Despite hypogonadism generally causing incomplete, delayed, and sometimes disordered pubertal development, in approximately 15–20% of patients of both sexes, premature adrenarche or precocious puberty often occurs [35, 46]. …”

“…Cryptorchidism is present in over 80% of boys from birth [35, 36]. At present there is no consensus in the literature as to the best treatment to use.…”

“…(b) Precocious sdrenarche and early puberty : Isolated premature pubarche has been reported in 14% and precocious puberty in 4% of males and females [35, 82, 83]. There is no consensus as to the management of either of these conditions.…”

Etiology and Treatment of Hypogonadism in Adolescents

“…In girls, findings may be less remarkable and include hypoplasia of the clitoris or labia minora, primary amenorrhea, and delayed puberty. 33 However, a wide spectrum of hypogonadism exists in PWS, with some women achieving fertility without hormone replacement therapy. 34,35 …”