Progestogen intolerance and compliance with hormone replacement therapy in menopausal women

It is vital that we maximize compliance if patients are to receive the full benefits from hormone replacement therapy (HRT). One of the main factors for reduced compliance is that of progestogen intolerance. Progestogens have a variety of effects apart from the one for which their use was intended, that of secretory transformation of the endometrium. Endometrial effects vary between individuals and between different progestogens, leading to bleeding problems. Symptoms of fluid retention are produced by the sodium-retaining effect on the renin-aldosterone system. The nor-testosterone-derived progestogens can have adverse effects on skin, lipids, vasculature and insulin resistance. Negative mood effects are produced by most progestogens due to the effect on neurotransmitters via central nervous system progesterone receptors. Manipulation of the dosage and duration of progestogen, continuous administration of a low dose of progestogen and a reduction in the number of progestogenic episodes can be used to improve compliance. The progestogen and progesterone releasing coils and vaginal progesterone gel minimize systemic side effects and bleeding. Adverse effects can also be avoided by making use of the progesterone receptor-specific progestogens such as the pregnanes (e.g. cyproterone), nor-pregnanes (e.g. nomegestrol) and progesterone itself. Hysterectomy remains an option for the severely progestogen-intolerant woman. In the future, progestogen intolerance may not be an issue if selective oestrogen receptor modulators provide a complete alternative to HRT.