What are the treatment options for a woman experiencing perimenopause?

Perimenopause Treatment

For women experiencing perimenopause, hormone therapy (combined estrogen-progestin for those with a uterus, estrogen-alone for those without) remains the most effective treatment for vasomotor symptoms, reducing hot flashes by approximately 75%, and should be initiated at the lowest effective dose when symptoms are bothersome, with transdermal estradiol 50 μg twice weekly plus micronized progesterone 200 mg nightly as the preferred first-line regimen. 1, 2

Initial Assessment and Risk Stratification

Before initiating any therapy, evaluate for absolute contraindications to hormone therapy including: 2

• History of breast cancer or other hormone-sensitive malignancies
• Active or prior venous thromboembolism or stroke
• Coronary heart disease or myocardial infarction
• Active liver disease
• Antiphospholipid syndrome or positive antiphospholipid antibodies

First-Line Treatment: Hormone Therapy

For Women WITH an Intact Uterus

Transdermal estradiol 50 μg patch (changed twice weekly) PLUS micronized progesterone 200 mg orally at bedtime is the preferred regimen. 1, 2 This combination:

• Reduces vasomotor symptoms by 75% 1
• Provides endometrial protection (reducing endometrial cancer risk by 90%) 2
• Has lower thrombotic and cardiovascular risk compared to oral formulations 1, 2
• Micronized progesterone carries lower breast cancer and VTE risk than synthetic progestins 1

For Women WITHOUT a Uterus (Post-Hysterectomy)

Transdermal estradiol 50 μg patch alone (changed twice weekly) is the preferred regimen. 1, 2 Estrogen-alone therapy:

• Shows NO increased breast cancer risk and may be protective (RR 0.80) 1, 2
• Reduces vasomotor symptoms by 75% 1
• Avoids unnecessary progestin exposure 2

Duration and Monitoring

• Use the lowest effective dose for the shortest duration necessary 1, 2
• Reassess annually for ongoing symptom burden and attempt dose reduction 2
• For perimenopausal women, continue until symptoms resolve or until age 60 (whichever comes first), then reassess 2
• The risk-benefit profile is most favorable for women under 60 or within 10 years of menopause onset 1, 2

Second-Line Non-Hormonal Options

For Vasomotor Symptoms (When HRT Contraindicated or Declined)

SNRIs are the most effective non-hormonal option, reducing hot flash intensity and severity by 40-65%. 1

• Venlafaxine is first-line among SNRIs 1
• SSRIs are alternatives, though avoid paroxetine and fluoxetine in women on tamoxifen due to CYP2D6 inhibition 1

Gabapentin is an effective alternative, particularly for women with nighttime symptoms. 1

• Typical dosing: 300-900 mg daily in divided doses 1

For Genitourinary Symptoms

Low-dose vaginal estrogen is highly effective (60-80% symptom improvement) with minimal systemic absorption. 1

• Options include vaginal rings, suppositories, or creams 1
• Can be used even in women where systemic HRT is contraindicated 1

Non-hormonal alternatives for vaginal dryness: 1

• Silicone-based lubricants (longer-lasting than water-based) 1
• Vaginal moisturizers (50% symptom reduction) 1

Lifestyle and Behavioral Interventions

These should be recommended for ALL perimenopausal women: 3, 1

• Weight loss (≥10% body weight) increases likelihood of eliminating hot flashes 3
• Smoking cessation improves frequency and severity of hot flashes 3
• Cognitive behavioral therapy (CBT) reduces perceived burden of hot flashes 3, 1
• Environmental modifications: cool room temperatures, layered clothing 1
• Regular exercise: while not proven to reduce hot flashes specifically, provides overall health benefits 3

Risk-Benefit Counseling for Hormone Therapy

For every 10,000 women taking combined estrogen-progestin for 1 year: 1, 2

• Risks: 7 additional CHD events, 8 more strokes, 8 more pulmonary emboli, 8 more invasive breast cancers
• Benefits: 6 fewer colorectal cancers, 5 fewer hip fractures, 75% reduction in vasomotor symptoms

The absolute risks are modest but increase with duration beyond 5 years. 1, 2

Critical Pitfalls to Avoid

• Never initiate HRT solely for chronic disease prevention (osteoporosis, cardiovascular disease) in asymptomatic women 1, 2
• Never use custom compounded bioidentical hormones or pellets due to lack of safety and efficacy data 2
• Never continue HRT beyond symptom management needs as breast cancer risk increases with duration 1, 2
• Never use oral estrogen as first-line when transdermal is available due to higher VTE and stroke risk 1, 2
• Never use synthetic progestins (medroxyprogesterone acetate) when micronized progesterone is available due to higher breast cancer and VTE risk 1, 2

Special Populations

Women Over 60 or >10 Years Post-Menopause

• HRT initiation is not recommended in this population 2
• If already on HRT at age 65, reassess necessity and attempt discontinuation 2
• If continuation is essential, use the absolute lowest effective dose 2

Women with Premature Ovarian Insufficiency (Before Age 40)

• HRT should be initiated immediately and continued until at least age 51 2
• This is for health preservation, not just symptom management 2

Contraception Considerations

Perimenopausal women remain at risk for unintended pregnancy and should use effective contraception until menopause is confirmed (12 months of amenorrhea). 4