Nomegestrol acetate: pharmacology, safety profile and therapeutic efficacy

This review summarizes the pharmacology, safety and clinical efficacy of nomegestrol acetate, based on the available published literature, and assesses the pharmacological characteristics that underlie a role in different gynaecological disorders and hormone replacement therapy (HRT), and a potential role in combination estrogen/progestogen oral contraception. Nomegestrol acetate is a potent, orally active progestogen with a favourable tolerability profile and neutral metabolic characteristics. Unlike the majority of older progestogens, which were 19-nortestosterone derivatives synthesized primarily for their antigonadotropic activity as a component of hormonal contraception in combination with an estrogen, nomegestrol acetate is a 19-norprogesterone derivative designed to bind specifically to the progesterone receptor, and is relatively lacking in affinity for other steroid receptors. Nomegestrol acetate exerts strong antiestrogenic effects at the level of the endometrium and has potent antigonadotropic activity, but without any residual androgenic or glucocorticoid properties. At a dosage of 1.25 mg/day, nomegestrol acetate inhibits ovulation while permitting follicle growth, whereas at dosages of 2.5 or 5 mg/day, both ovulation and follicle development are suppressed. The antigonadotropic action of nomegestrol acetate is mediated, like other progestins, at the hypothalamic and pituitary level. Moreover, nomegestrol acetate has partial antiandrogenic activity. Absorption of nomegestrol acetate is rapid after oral administration, reaching a peak serum concentration within 4 hours, with a terminal half-life of approximately 50 hours. Nomegestrol acetate has been used successfully for the treatment of some gynaecological disorders (menstrual disturbances, dysmenorrhoea, premenstrual syndrome) and as a component of HRT in combination with estradiol for the relief of menopausal symptoms; it has been approved in Europe as monotherapy for the treatment of the menopausal syndrome, uterine diseases and menorrhagia, and in combination with an estrogen for the treatment of menopausal symptoms. In vitro data suggest that nomegestrol acetate preserves the beneficial haemostatic effects of estrogen; furthermore, nomegestrol acetate has a neutral or beneficial effect on lipid profiles, and does not adversely affect glucose metabolism or bodyweight. Nomegestrol acetate has shown a lack of profilerative activity in normal and cancerous breast tissue, and does not have a deleterious effect on bone remodelling. These potent antigonadotropic properties, and other beneficial metabolic and pharmacological characteristics, suggest that nomegestrol acetate can be an effective progestogen for use in combination with an estrogen in oral estrogen/progestogen contraceptive treatment and in HRT, while it also provides some non-contraceptive benefits for women's health.