GnRH analogue use in postmenopausal hyperandrogenism: long-term remission

Abstract

To the Editor, The medical therapy of postmenopausal hyperandrogenism remains poorly described. The effectiveness of short-term GnRH analogues in suppressing androgens is generally indicative of the ovarian origin of the androgen production, and its benign nature [1–3], although very rarely adrenal tumours secreting androgen responsive to GnRH agonist have been reported [4]. Here we report a rare case of longterm GnRH analogue-induced suppression of androgens of ovarian origin. A 78-year-old woman was referred for investigation of severe hyperandrogenism. She had noticed the progressive appearance of hirsuties over her face and body over a period of 3–4 years, her face becoming plethoric, with concomitant deepening of her voice which became more husky, and increasing temporal recession. She had gained around 10 kg in weight, and reported increased libido for 2 years. She was treated for hypertension with agents not considered to be causative of hirsutism. Clinical examination confirmed significant hirsutism: both her serum testosterone and androstenedione levels were markedly elevated at 21.3 nmol/l (NR \ 2.9) and 17.8 nmol/l (normal 3–8), respectively, with a normal serum DHEAS. Serum testosterone failed to suppress on a low-dose dexamethasone suppression test (16.8 nmol/l at 48 h, with normal suppression of cortisol). Her serum gonadotrophins were appropriately elevated for the menopause (FSH 40.2 U/l, NR [ 25; LH 21.9 U/l, NR [ 16), and her estradiol appropriately low (157 pmol/L, NR 18.4–201). Basal 17-hydroxyprogesterone was normal, excluding the common form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Imaging (CT scanning, MRI) did not show any adrenal or ovarian abnormality, while a transvaginal US scan showed a slightly bulky uterus without thickening of the endometrium. The most likely diagnosis at this stage was either bilateral ovarian hilar cell hyperplasia or hyperthecosis, or a small Leydig cell tumour in one or both ovaries. Ovarian venous catheterisation was not considered as we have previously noticed the lack of utility of this procedure in this situation [5]. A single longacting 10.8 mg subcutaneous injection of goserelin (Zoladex LA, AstraZeneca) was given which induced the suppression of the serum testosterone level to 0.7 nmol/l 2 months later. The GnRH dependence of androgen secretion was taken to be indicative of an ovarian origin. Treatment with the GnRH agonist was continued for 17 months (subcutaneous injections every 3 months), and her serum testosterone levels remained within the normal range (0.9 and 1.6 nmol/l) for a further 27 months off treatment. Significant improvement of her symptoms was noticed; 11 months later the patient died from overwhelming sepsis due to methicillin-resistant S. aureus unrelated to her endocrine condition. In this case, in addition to representing a functional diagnostic tool, the use of GnRH analogues offers a valuable therapeutic approach which is a particularly useful mode of therapy in patients for whom surgical intervention is not appropriate for diverse reasons. Indeed, only rare M. Gueorguiev Department of Endocrinology, St Bartholomew’s Hospital, London EC1A 7BE, UK