Progestogens as a component of menopausal hormone therapy: the right molecule makes the difference

Optimizing menopausal hormone therapy (MHT) requires an awareness of the benefits and risks associated with the available treatments. This narrative review, which is based on the proceedings of an Advisory Board meeting and supplemented by relevant articles identified in literature searches, examines the role of progestogens in MHT, with the aim of providing practical recommendations for prescribing physicians. Progestogens are an essential component of MHT in menopausal women with a uterus to prevent endometrial hyperplasia and reduce the risk of cancer associated with using unopposed estrogen. Progestogens include natural progesterone, dydrogesterone (a stereoisomer of progesterone), and a range of synthetic compounds. Structural differences and varying affinities for other steroid receptors (androgen, glucocorticoid, and mineralocorticoid) confer a unique biological and clinical profile to each progestogen that must be considered during treatment selection. MHT, including the progestogen component, should be tailored to each woman, starting with an estrogen and a progestogen that has the safest profile with respect to breast cancer and cardiovascular effects, while addressing patient-specific needs, risk factors, and treatment goals. Micronized progesterone and dydrogesterone appear to be the safest options, with lower associated cardiovascular, thromboembolic, and breast cancer risks compared with other progestogens, and are the first-choice options for use in ‘special situations,’ such as in women with high-density breast tissue, diabetes, obesity, smoking, and risk factors for venous thromboembolism, among others.