Clinical aspects of LHRH analogues in gynaecology: a review

Abstract

LHRH agonists are synthetic peptide analogues of hypothalamic luteinizing hormone releasing hormone (LHRH) with superior potency and longer duration of gonadotrophin release. Paradoxically, repeated administration causes pituitary desensitization with diminished gonadotrophin and oestradiol secretion. A state of hypogonadotrophic hypogonadism is reversibly induced; plasma oestrogen can be reduced to castrate levels. LHRH agonists reliably induce anovulation but are unlikely to replace existing contraceptive methods in most normal women. By contrast these agents offer, for the first time, the prospect of inducing a reversible pseudomenopause essentially free of side-effects. LHRH analogues promise to have a profound impact upon the management of a diverse range of oestrogen-dependent gynaecological diseases both benign and malignant. In particular, they may shortly become the gynaecological treatment of choice in endometriosis, as well as becoming part of the management of common gynaecological disorders such as dysfunctional uterine bleeding and uterine fibroids. R.

A new way to induce oestrogen-deficiency osteopaenia in the rat: comparison of the effects of surgical ovariectomy and administration of the LHRH agonist buserelin on bone resorption and composition

“…There is concern that increased long-term use of LHRH analogues may be associated with unwanted sequelae of hypoestrogenism, such as osteopaenia (McLachlan et al 1986;Gudmundsson et al 1987;Henzl et al 1988). Our present findings in the rat con¬ firm, by direct skeletal analysis, work in women which suggests that LHRH agonists cause bone loss (Cann et al 1987;Devogelaer et al 1987;Matta et al 1987).…”

“…Currently, there is widespread con¬ cern that increased prolonged use of these agonists to treat endometriosis will cause sustained oestrogendeficiency bone loss in young women of premenopausal age (McLachlan, Healy & Burger, 1986;Cann, Henzl, Burry et al 1987;Devogelaer, Nagant de Deuxchaisnes, Donnez & Thomas, 1987;Gudmundsson, Ljunghall, Bergquist et al 1987;Matta, Shaw, Hesp & Katz, 1987;Henzl, Corson, Moghissi et ai. 1988).…”

Long‐term follow‐up of patients with uterine fibroids after treatment with the LHRH agonist buserelin

“…We have demonstrated in a longitudinal study that when buserelin was administered intranasally, 400 pg three times daily, to 13 premenopausal women there was an associated small but significant reduction of 6% in their mean lumbar vertebral trabecular bone density at the end of 6 months treatment; this loss was reversed 6 months after discontinuation of therapy (Matta et al 1987;Matta et al 1088h). For the same reason we have reservations about advocating the use of LHRH agonists in perimenopausal symptomatic women (McLachlan et al 1986;Van Leusden 1986;Rolland et al 1986;Friedman et al 1987) with the aim of controlling their symptoms until natural occurrence of the menopause. Accelerated bone loss occurs in oophorectomized premenopausal women and in all postmenopausal women; it is minimized by oestrogen therapy.…”

Uterine fibroids: A clinical review

“…This time of commencement, however, rules out the possibility of accidental administration during pregnancy. When begun in the luteal phase of the menstrual cycle, the elevation of gonadotrophins and sex steroids is restricted to this phase and normal menstruation occurs without a subsequent withdrawal blced in the following cycle (Fraser & Sandow 1985;Hcaly et al 1986;McLachlan et al 1986).…”