Perimenopause Treatment
Primary Recommendation
Initiate transdermal estradiol patches (50 μg daily) combined with micronized progesterone (200 mg daily) at symptom onset for women with an intact uterus, or estradiol alone for post-hysterectomy women—this is the most effective treatment for bothersome perimenopausal symptoms. 1
Treatment Algorithm
Step 1: Screen for Absolute Contraindications
Before initiating any hormone therapy, exclude the following absolute contraindications 1:
- History of breast cancer or hormone-sensitive malignancies
- Active or history of venous thromboembolism or stroke
- Coronary heart disease
- Active liver disease
- Antiphospholipid syndrome or positive antiphospholipid antibodies
- Unexplained vaginal bleeding
If any contraindication is present, proceed directly to non-hormonal options (Step 3). 1
Step 2: Initiate Hormone Therapy (First-Line for Eligible Women)
Route Selection: Transdermal is Superior
Always choose transdermal estradiol patches over oral formulations because they bypass hepatic first-pass metabolism, reducing cardiovascular and thromboembolic risks while maintaining physiological estradiol levels. 1, 2
Specific Regimens Based on Uterine Status
For women WITH an intact uterus (progestin is mandatory to prevent endometrial cancer) 1:
- Preferred option: Combined estradiol/progestin patches (50 μg estradiol + 10 μg levonorgestrel daily)
- Alternative: Transdermal estradiol 50 μg daily PLUS oral micronized progesterone 200 mg daily
For women WITHOUT a uterus (post-hysterectomy) 1:
- Transdermal estradiol 50 μg daily alone
Critical Timing Consideration
Do not delay hormone therapy initiation until after menopause is complete—perimenopause is the appropriate time to start treatment for bothersome symptoms. 1 The benefit-risk profile is most favorable for women under 60 years of age or within 10 years of menopause onset. 2
Step 3: Non-Hormonal Alternatives (For Women with Contraindications or Who Decline HT)
For Vasomotor Symptoms and Mood
SSRIs are first-line non-hormonal pharmacologic options 1:
- Paroxetine
- Sertraline
- Citalopram
- Fluoxetine
Gabapentin is recommended for hot flashes, particularly beneficial for nighttime symptoms. 1
Note: A new class of neurokinin B antagonists shows promise for vasomotor symptoms, sleep, and mood issues, though SSRIs remain the established first-line recommendation. 3
For Genitourinary Symptoms
First-line: Vaginal moisturizers and lubricants reduce symptom severity by up to 50% with no systemic absorption. 1
Second-line: Low-dose vaginal estrogen preparations (rings, suppositories, creams) improve symptoms by 60-80% with minimal systemic absorption, but should be avoided in women with hormone-sensitive cancers. 1
Duration and Monitoring Strategy
Use the lowest effective dose for the shortest duration needed to control symptoms, typically continuing therapy through the peak symptom years (4-7 years), then attempt gradual discontinuation. 1
Special exception: For women with premature menopause (before age 45), hormone therapy should be continued until at least age 51 (average age of natural menopause), then reassessed. 1, 2
Risk-Benefit Data for Informed Consent
For every 10,000 women taking combined estrogen-progestin therapy for 1 year 1, 2:
Risks:
- 8 additional invasive breast cancers
- 8 additional strokes
- 8 additional pulmonary emboli
- 7 additional coronary heart disease events
Benefits:
- 6 fewer colorectal cancers
- 5 fewer hip fractures
The absolute increase in risk is modest and should be weighed against the significant quality of life improvements from symptom relief. 1
Critical Pitfalls to Avoid
Never use estrogen without progestin in women with an intact uterus—this increases endometrial cancer risk by failing to provide the approximately 90% risk reduction that progestin confers. 1, 2
Never initiate hormone therapy solely for osteoporosis or cardiovascular disease prevention—the benefits do not outweigh the risks for these indications. 1, 2
Never start systemic hormone therapy in women over 60 or more than 10 years past menopause onset unless using the absolute lowest effective dose for severe persistent symptoms, as cardiovascular and thromboembolic risks substantially increase. 2, 4
Do not use oral estrogen formulations when transdermal options are available—oral routes have less favorable cardiovascular and thrombotic risk profiles due to hepatic first-pass metabolism. 1, 2