What are the treatment options for menopause (menopause tx) symptoms?

Treatment Options for Menopause Symptoms

For symptomatic postmenopausal women under age 60 or within 10 years of menopause onset without contraindications, menopausal hormone therapy (MHT) is the most effective treatment, reducing vasomotor symptoms by approximately 75% compared to placebo, but nonhormonal pharmacologic options should be considered first-line for most women due to safety considerations. 1, 2

First-Line Nonhormonal Pharmacologic Treatment for Hot Flashes

Start with gabapentin 900 mg/day at bedtime as first-line therapy for moderate to severe hot flashes, reducing severity by 46% compared to 15% with placebo, with equivalent efficacy to estrogen and no drug interactions. 2

• Gabapentin has no absolute contraindications and is safer than SSRIs/SNRIs in complex medication regimens, making it ideal for patients on multiple medications or taking tamoxifen. 2
• Side effects affect up to 20% of patients but improve after the first week and largely resolve by week 4. 2
• Particularly useful when taken at bedtime for patients whose sleep is disturbed by hot flashes. 2

Alternative: Venlafaxine 37.5 mg daily, increasing to 75 mg after 1 week, reduces hot flash scores by 37-61% and is preferred when rapid onset is prioritized or gabapentin is ineffective. 2

• Venlafaxine is preferred by 68% of patients over gabapentin despite similar efficacy. 2
• Must be tapered gradually on discontinuation to minimize withdrawal symptoms. 2

Paroxetine 7.5-20 mg daily reduces hot flash frequency, severity, and nighttime awakenings by 62-65%. 2

• CRITICAL WARNING: Avoid paroxetine and fluoxetine in women taking tamoxifen due to CYP2D6 inhibition that reduces tamoxifen efficacy. 1, 2
• Also contraindicated with monoamine oxidase inhibitors and should be avoided in bipolar disorder due to risk of inducing mania. 2

Review efficacy at 2-4 weeks for SSRIs/SNRIs and 4-6 weeks for gabapentin; if intolerant or ineffective, switch to another nonhormonal agent. 2

Treatment for Vaginal Symptoms (Genitourinary Syndrome of Menopause)

Vaginal moisturizers, gels, and oils provide effective relief for vaginal dryness and should be used regularly for comfort. 3

• Lubricants should be used specifically for sexual activity to address discomfort during intercourse. 3
• Silicone-based products may last longer than water-based or glycerin-based products. 1
• Topical vitamin D or E can be applied vaginally for additional symptom relief. 3
• These products work through non-hormonal mechanisms and are safe for all women, including those with contraindications to hormonal therapy. 3

For persistent symptoms: Low-dose vaginal estrogen tablets or estradiol vaginal rings are highly effective for vaginal atrophy, with results typically taking 6-12 weeks to become apparent. 1

• Not recommended for women on aromatase inhibitors. 1
• Safety in women with a history of breast cancer is not well established. 1

Nonpharmacologic Approaches

Weight loss of ≥10% of body weight may eliminate hot flash symptoms entirely in overweight or obese women. 3, 1, 2

Acupuncture is safe and effective, with some studies showing equivalence or superiority to venlafaxine or gabapentin. 2

• Not recommended for breast cancer survivors with prior axillary surgery on the affected arm. 2

Cognitive behavioral therapy (CBT) reduces the perceived burden of hot flashes and improves quality of life. 1, 2

Hypnosis showed a 59% decrease in daily hot flashes and significant improvement in work, social activities, sleep, mood, concentration, and sexuality. 2

Paced respiration training and structured relaxation techniques for 20 minutes daily show significant benefit. 2

Lifestyle modifications:

• Smoking cessation improves frequency and severity of hot flashes. 1, 2
• Limiting alcohol intake if it triggers hot flashes. 3, 1
• Environmental modifications: keeping rooms cool, dressing in layers, using fans. 3
• Avoiding spicy foods and caffeine may help reduce hot flash frequency, though results are variable. 3

Menopausal Hormone Therapy (MHT)

MHT is the most effective treatment for vasomotor symptoms, reducing hot flashes by approximately 75% compared to placebo, but should only be used when nonhormonal options fail or for women with severe symptoms affecting quality of life. 2

Use at the lowest effective dose for the shortest duration consistent with treatment goals. 4, 5

Formulation Selection

Transdermal estrogen formulations are preferred due to lower rates of venous thromboembolism and stroke compared to oral formulations. 2

• Start with estradiol gel 0.1%, 0.25 grams applied once daily to the upper thigh, adjusting up to maximum 1.25 grams as needed. 5
• Apply to alternating thighs to avoid skin irritation. 5
• Allow gel to dry before dressing; do not wash application site within 1 hour. 5

For women with an intact uterus: Combination estrogen and progestin is required to reduce endometrial cancer risk. 1, 5

• Micronized progestin may be preferred over medroxyprogesterone acetate due to lower rates of VTE and breast cancer risk. 2

For women without a uterus: Estrogen alone is appropriate. 1, 5

• Exception: Hysterectomized women with history of endometriosis may need a progestogen. 5

Absolute Contraindications to MHT

• History of hormone-related cancers (breast, endometrial). 1, 2, 5
• Undiagnosed abnormal vaginal bleeding. 1, 5
• Active or recent thromboembolic events (DVT, PE, stroke, MI). 5
• Active liver disease. 1, 5
• Pregnancy. 1, 5
• Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders. 5

Timing Considerations

Benefits may exceed risks for symptomatic postmenopausal women under age 60 or within 10 years of menopause onset. 4, 1

• Early initiation of HT close to menopause is more likely to have maximal benefits and lowest risks. 6
• Risks (venous thromboembolism, CHD, stroke) appear within the first 1-2 years of therapy. 4
• Breast cancer risk increases with longer-term use (>3-5 years). 4, 2

Important Safety Warnings

Combined estrogen/progestogen therapy increases breast cancer risk when used for more than 3-5 years, and increases risk of stroke and venous thromboembolism. 2

The WHI trials demonstrated increased risks of PE, DVT, stroke, and MI in women 50-79 years of age receiving daily oral conjugated equine estrogen 0.625 mg plus medroxyprogesterone acetate 2.5 mg. 5

Do not use MHT for prevention of cardiovascular disease or dementia. 4, 5

Reevaluate postmenopausal women periodically as clinically appropriate to determine whether treatment is still necessary. 5

Limited Efficacy Options

Vitamin E 800 IU daily has minimal efficacy but may be reasonable for patients requesting "natural" treatment. 3, 2

• WARNING: Doses exceeding 400 IU/day are associated with increased all-cause mortality and should be avoided. 3, 2

Custom-compounded bioidentical hormones have no data supporting claims of being safer or more effective than standard hormone therapies. 1

• The FDA has not approved any type or class of bioidentical hormone therapy for prevention of chronic diseases. 4

Common Pitfalls to Avoid

• Never prescribe paroxetine or fluoxetine to women taking tamoxifen due to CYP2D6 inhibition. 1, 2
• Do not use MHT in women over age 60 or more than 10 years past menopause onset without careful risk assessment, as risks exceed benefits. 4, 1
• Always add progestin to estrogen in women with an intact uterus to prevent endometrial cancer. 1, 5
• Recognize the robust placebo response (up to 70% in some studies) when evaluating treatment efficacy. 2
• Screen for cardiovascular and breast cancer risk before initiating MHT and recommend the most appropriate therapy depending on risk/benefit considerations. 7