Oestrogen Therapy Risks in Postmenopausal Women
All four options (A, B, C, D) represent documented risks of oestrogen therapy, but they differ critically based on whether oestrogen is used alone or combined with progestogen, making options A, C, and D definitively correct depending on the specific regimen.
Thrombophlebitis/Deep Venous Thrombosis (Option A) - CORRECT
Both unopposed oestrogen and combined oestrogen-progestogen therapy significantly increase thrombophlebitis risk. 1
- Unopposed oestrogen is associated with a small but definite increase in DVT risk 1
- Combined oestrogen-progestogen therapy carries convincing evidence of a small increased risk for DVT and pulmonary embolism 1
- Meta-analysis of randomized controlled trials showed venous thromboembolism risk ratio of 2.14 (95% CI 1.64-2.81) with HRT 1
- The risk is highest within the first year of use (RR 3.49,95% CI 2.33-5.59) 1
- Women's Health Initiative confirmed a twofold increased rate of venous thromboembolic disease (RR 2.11,95% CI 1.26-3.55) with combined therapy 1
Hepatic Adenoma (Option B) - NOT DOCUMENTED
The provided evidence does not establish an association between postmenopausal oestrogen therapy and hepatic adenoma. While gallbladder disease is documented as a moderate harm with both unopposed oestrogen and combined therapy 1, hepatic adenoma is not mentioned in the high-quality guidelines reviewed.
Endometrial Cancer (Option C) - CORRECT FOR UNOPPOSED OESTROGEN
Unopposed oestrogen dramatically increases endometrial cancer risk, which is precisely why progestogen must be added for women with an intact uterus. 1, 2
- Unopposed oestrogen significantly increases endometrial cancer risk (RR 2.3,95% CI 2.1-2.5) 1, 2
- Risk escalates dramatically with duration: relative risk reaches 9.5 after 10 years of unopposed oestrogen use 1, 2
- The elevated risk persists for at least 5 years after discontinuation 1, 2
- This is the fundamental reason oestrogen without progestogen has been restricted to women who have had a hysterectomy 1, 2
- Combined oestrogen-progestogen regimens actually reduce endometrial cancer risk (RR 0.4,95% CI 0.2-0.6 in cohort studies) 1
- The WHI trial showed no increase in endometrial cancer with combined therapy (RR 0.83,95% CI 0.29-2.32) 1
Breast Cancer (Option D) - CORRECT FOR COMBINED THERAPY ONLY
Combined oestrogen-progestogen therapy increases breast cancer risk, but unopposed oestrogen paradoxically reduces it. 1, 2
Combined Oestrogen-Progestogen:
- Convincing evidence of a small increase in invasive breast cancer incidence (RR 1.26,95% CI 1.00-1.59) 1, 2
- Translates to 8 additional invasive breast cancers per 10,000 women-years 1
- Adequate evidence of a small increase in breast cancer deaths 1
Unopposed Oestrogen (Women Post-Hysterectomy):
- Adequate evidence shows a small reduction in invasive breast cancer risk 1, 2
- About 8 fewer cases per 10,000 person-years 2
- About 2 fewer breast cancer deaths per 10,000 person-years 2
Critical Clinical Algorithm
For women WITH an intact uterus:
- Must use combined oestrogen-progestogen therapy 1, 2
- Increased risks: thrombophlebitis (A), breast cancer (D) 1, 2
- Decreased risk: endometrial cancer (C) - progestogen is protective 1, 2
For women WITHOUT a uterus (post-hysterectomy):
- Can use unopposed oestrogen 1, 2
- Increased risks: thrombophlebitis (A), endometrial cancer if uterus present (C) 1, 2
- Decreased risk: breast cancer (D) 1, 2
Common Pitfalls to Avoid
- Never assume all oestrogen formulations carry equal risks - the progestogen component fundamentally alters the risk profile, particularly for endometrial and breast cancer 1, 2
- Do not overlook that unopposed oestrogen is contraindicated in women with an intact uterus due to the dramatic endometrial cancer risk (RR up to 9.5 with long-term use) 1, 2
- Recognize that breast cancer risk increases with duration of combined therapy, particularly beyond 5 years 1
- The thrombophlebitis risk is highest in the first year of therapy (RR 3.49), requiring heightened vigilance during initiation 1