Objective: To create an evidence-based position statement regarding the role of progestogen in postmenopausal hormone therapy (estrogen plus a progestogen, or EPT) for the management of menopause-related symptoms.
Design: NAMS followed the general principles established for evidence-based guidelines to create this document. Clinicians and researchers acknowledged to be experts in the field of postmenopausal hormone therapy were enlisted to review the evidence obtained from the medical literature and develop a position statement for approval by the NAMS Board of Trustees.
Results: The primary role of progestogen in postmenopausal hormone therapy is endometrial protection. Unopposed estrogen therapy (ET) is associated with a significantly increased risk of endometrial hyperplasia and adenocarcinoma. Adding the appropriate dose and duration of progestogen to ET has been shown to lower that risk to the level found in never-users of ET. The clinical goal of progestogen in EPT is to provide endometrial protection while maintaining estrogen benefits and minimizing progestogen-induced side effects, particularly uterine bleeding. EPT discontinuance correlates with uterine bleeding-women with more days of amenorrhea have higher rates of continuance. All US Food and Drug Administration-approved progestogen formulations will provide endometrial protection if the dose and duration are adequate. Progestogens may diminish the beneficial effects of ET on cardiovascular risk factors. However, no EPT (or ET) regimen should be initiated for the primary or secondary prevention of cardiovascular heart disease. Some progestogens may negatively affect mood. Adding progestogen to ET does not decrease the breast cancer risk, although it does not seem to increase mortality. Progestogen increases mammographic density, which is reversed after discontinuation of use. Progestogen has limited effect on the bone-enhancing action of ET. In general, the side effects of added progestogen are mild, although they may be severe in a small percentage of women.
Conclusions: Progestogen should be added to ET for all postmenopausal women with an intact uterus to prevent the elevated risk of estrogen-induced endometrial hyperplasia and adenocarcinoma. There is no consensus on a preferred regimen for all women. By changing the progestogen type, route, or regimen, clinicians can individualize therapy to minimize side effects, especially uterine bleeding, and limit any effects on ET benefits while providing adequate endometrial protection.