Progesterone Administration in Women Without a Uterus
In women who have had a hysterectomy, progesterone is generally not needed and should not be routinely administered, as the primary indication for progesterone is endometrial protection, which is irrelevant without a uterus. 1, 2, 3
Primary Rationale
Progesterone's main role is endometrial protection: The use of estrogen without progestin has been restricted to women who have had a hysterectomy specifically because unopposed estrogen increases the risk for endometrial cancer in women with an intact uterus 1, 2
After hysterectomy, estrogen-only therapy is appropriate: When the uterus is absent, estrogen treatment alone is all that is needed for menopausal symptoms such as hot flashes and genital atrophic symptoms 3
Adding progesterone may cause harm without benefit: Multiple lines of evidence suggest that regimens containing both estrogen and progestogen versus estrogen alone are associated with a greater relative risk of breast cancer without additional improvement in relief of hot flashes or vaginal symptoms 3
Specific Exceptions Where Progesterone May Be Indicated
Residual endometriosis: The primary reason to add a progestogen to an estrogen-only therapy regimen after hysterectomy is to reduce the risk for unopposed estrogen-dependent conditions, chief among which is endometriosis 3
History of endometrial neoplasia: Women with a history of endometrial cancer who have undergone hysterectomy may require progesterone if residual endometrial tissue remains 3
Safety Considerations
Breast cancer risk: The U.S. Preventive Services Task Force found convincing evidence of a small increase in the incidence of invasive breast cancer and adequate evidence of a small increase in breast cancer deaths with combined estrogen and progestin therapy 1
Cardiovascular effects: Data suggest an attenuation of the potential cardiovascular benefit of estrogen therapy when progestogen is added after hysterectomy 3
No additional bone protection: There is no better protection against bone fractures when both estrogen and progestogen are used compared to estrogen alone 3
Clinical Bottom Line
For most patients after hysterectomy, current literature results favor not including a progestogen 3. The decision should involve an individualized risk/benefit analysis, but the default position is estrogen-only therapy unless specific contraindications exist such as residual endometriosis 3.