Does a postmenopausal female patient without a uterus (having undergone a hysterectomy) require progesterone therapy?

No, Women Without a Uterus Do Not Need Progesterone

Women who have undergone a hysterectomy should receive estrogen-alone therapy and do not require progesterone supplementation. 1, 2

The Fundamental Principle: Progesterone's Sole Purpose in HRT

The only reason progesterone is added to estrogen therapy is to protect the endometrium from cancer risk. 1, 2

Why Progesterone is Required (Only With an Intact Uterus)

• Unopposed estrogen dramatically increases endometrial cancer risk with a relative risk of 2.3 (95% CI 2.1-2.5), escalating to 9.5-fold after 10 years of use 2
• The elevated endometrial cancer risk persists for at least 5 years after discontinuing unopposed estrogen 2
• Adding progesterone reduces endometrial cancer risk by approximately 90% compared to unopposed estrogen 1, 2
• This endometrial protection is the fundamental reason estrogen without progestin has been restricted to women who have had a hysterectomy 2

Why Progesterone Should Be Avoided (Without a Uterus)

Progesterone actually increases health risks when there is no uterus to protect:

• Combined estrogen-progestin therapy increases invasive breast cancer risk (RR 1.26,95% CI 1.00-1.59) with 8 additional cases per 10,000 women-years 2
• Estrogen-only therapy paradoxically shows a small reduction in invasive breast cancer risk (about 8 fewer cases per 10,000 person-years) and breast cancer deaths (about 2 fewer deaths per 10,000 person-years) 2
• Combined estrogen-progestin carries convincing evidence of increased risk for DVT and pulmonary embolism beyond estrogen alone 2

Clinical Algorithm for Progesterone Decision-Making

Step 1: Determine uterine status

• Hysterectomy performed? → No progesterone needed 1, 2
• Uterus intact? → Progesterone mandatory 1, 2

Step 2: If uterus is absent

• Prescribe estrogen-alone therapy (transdermal estradiol 50 μg patch twice weekly preferred) 1
• Never add progesterone - it only increases risks without providing benefit 2

Step 3: If uterus is present

• Must add progesterone to prevent endometrial cancer 1, 2
• Preferred: Micronized progesterone 200 mg orally at bedtime (superior breast safety profile) 1
• Alternative: Medroxyprogesterone acetate 2.5 mg daily continuous or 10 mg for 12-14 days per month 1

Critical Clinical Pitfall to Avoid

Never prescribe progesterone to women who have had a hysterectomy - this is a common error that unnecessarily increases breast cancer and thrombotic risks without providing any benefit, since there is no endometrium to protect. 2

The American College of Obstetricians and Gynecologists explicitly states that estrogen-alone therapy is appropriate only for women who have had a hysterectomy, and women with an intact uterus require progestin addition to prevent endometrial cancer. 1