Management of Perimenopause Symptoms Related to Estrogen Deficiency
Menopausal hormone therapy (MHT) is the most effective treatment for managing vasomotor symptoms in perimenopausal women, with estrogen-progestin combinations for women with an intact uterus and estrogen alone for those without a uterus. 1
Understanding Perimenopause Symptoms
Perimenopause is characterized by:
- Vasomotor symptoms (hot flashes, night sweats)
- Vaginal dryness and sexual dysfunction
- Sleep disturbances
- Mood changes and cognitive dysfunction
- Arthralgias/myalgias
- Fatigue
- Changes in menstrual patterns
These symptoms significantly impact quality of life and are primarily related to fluctuating and eventually declining estrogen levels.
Treatment Options
First-Line: Menopausal Hormone Therapy (MHT)
MHT is the most effective option for vasomotor symptoms and should be used at the lowest effective dose for the shortest time needed 1:
For women with intact uterus: Combined estrogen-progestin therapy
- Conjugated equine estrogen (0.625 mg/day) with medroxyprogesterone acetate (2.5 mg/day) OR
- Transdermal estradiol (0.025-0.0375 mg/day patch) with micronized progesterone (200 mg orally for 12-14 days per month)
For women without uterus: Estrogen-only therapy
- Conjugated equine estrogen (0.625 mg/day) OR
- Transdermal estradiol (0.025-0.0375 mg/day patch)
Contraindications to MHT 1, 2:
- History of hormonally mediated cancers
- Abnormal vaginal bleeding
- Active or recent thromboembolic events
- Active liver disease
- Pregnancy
- History of stroke or heart attack in the past year
Non-Hormonal Pharmacologic Options
For women with contraindications to MHT or those who prefer non-hormonal approaches 1:
SSRIs/SNRIs (e.g., venlafaxine, paroxetine, desvenlafaxine)
- Effective for reducing hot flash frequency and severity
- Note: Side effects are common but usually manageable
Gabapentin
- Effective alternative for vasomotor symptoms
- Particularly useful for women with sleep disturbances
Clonidine
- Less effective than other options but may benefit some women
Vaginal Symptoms Management
For vaginal dryness, itching, and sexual discomfort 1:
- Vaginal moisturizers for regular use
- Lubricants for sexual activity
- Low-dose local estrogen preparations (rings, suppositories, creams) for more severe symptoms
- These have minimal systemic absorption and may be considered even in some cases where systemic MHT is contraindicated
Newer Treatment Options
Fezolinetant, a Neurokinin-3 receptor antagonist, is now available for treating vasomotor symptoms in postmenopausal women with contraindications to or aversion against steroid hormones 3. It works by modulating the thermoregulation center in the hypothalamus.
Special Considerations
Hormone Replacement After Cancer
For women with a history of germ cell ovarian cancer, hormone replacement therapy may be used safely 4. However, HRT should be avoided in women with hormone-dependent cancers such as ovarian granulosa cell tumors and other sex cord-stromal malignancies 4.
Duration of Treatment
Perimenopausal symptoms often last longer than previously thought - up to 11.8 years for women who experience symptoms beginning in early perimenopause 3. Regular follow-up (every 3-6 months) is recommended to evaluate continued need for therapy, compliance, and monitor for side effects 1, 2.
Mood Symptoms
Depressive symptoms may improve with estrogen therapy in perimenopausal women with mild symptoms, but those with moderate to severe depression typically require antidepressant therapy 5. The relationship between perimenopause and mood is complex, with some evidence suggesting a positive association between depressive symptoms and perimenopause, particularly in women with a prior history of depression 6.
Monitoring and Follow-up
Annual follow-up is recommended to evaluate:
- Continued need for therapy
- Compliance
- Blood pressure
- Weight
- Lipid profile
Risks of MHT
Combined estrogen-progestin therapy carries risks including:
- Increased risk of cardiovascular events (stroke, pulmonary embolism)
- Breast cancer
- Blood clots
- Dementia (particularly in women aged 60+ or >10 years post-menopause)
These risks must be weighed against the benefits in symptom relief and quality of life improvement.