Menopause

Background

• Menopause is a physiologic event characterized by loss of ovarian activity and permanent cessation of menses, diagnosed after 12 consecutive months of amenorrhea. This process occurs naturally, but can also be induced by medications, gynecologic surgery, chemotherapy, or radiation, often with sudden onset of symptoms in these circumstances.
• The mean age of onset of natural menopause is 51 years in North America, with perimenopausal (transitional) symptoms often seen in women aged 40-58 years.
• Symptoms associated with menopausal transition vary in duration and severity, and may include vasomotor symptoms (hot flashes) in > 50% of perimenopausal women, night sweats, insomnia, vaginal atrophy, and sexual dysfunction.
• Occurrence of vasomotor symptoms peaks about 1 year after the final menstrual period, with symptoms lasting an average of 4-10 years. Symptoms spontaneously cease within 5 years of onset for most women.
• About 50% of women are reported to have recurrent vasomotor symptoms after discontinuation of hormone replacement therapy.

Evaluation

• Testing beyond history and physical is not typically needed for diagnosis, but may help identify the stage of menopausal transition (Strong recommendation).
• Estradiol levels appear stable in early perimenopausal women but may decrease in late perimenopausal and postmenopausal women. Estradiol levels < 20 pg/mL may indicate menopause.
• Follicle-stimulating hormone (FSH) appears to have limited reliability for determining the start of perimenopause in women. FSH levels > 30-40 milliunits/mL may indicate menopause.
• Vaginal pH > 4.5 may indicate perimenopause or menopause.

Management

• Lifestyle modifications may help reduce menopausal symptoms, including diet, exercise, and mind-body therapies (Strong recommendation).
• Vasomotor symptoms of menopause may improve with environmental modifications, hormonal therapies (systemic or local), and nonhormonal therapies.
  • Layering of clothing, maintaining a lower ambient temperature, and consumption of cool drinks may help improve vasomotor symptoms associated with menopause (Strong recommendation).
  • Hormonal therapy with estrogen alone or in combination with progestin (for women with intact uterus) is the most effective treatment for vasomotor symptoms (Strong recommendation).
    • Low-dose and ultra-low-dose estrogen therapy is associated with fewer adverse effects than higher doses, and may reduce vasomotor symptoms in some women (Strong recommendation).
    • Transdermal or vaginal estrogen should be considered for vasomotor symptom relief in women with hypertension, hypercholesterolemia, or at increased risk of cholelithiasis (Strong recommendation).
  • Progestin-only medications, testosterone, and compounded bioidentical hormones have limited evidence to support their use for treatment of vasomotor symptoms (Weak recommendation).
  • Nonhormonal therapies for alleviation of vasomotor symptoms include selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), clonidine, and gabapentin.
    • Paroxetine 7.5 mg orally once daily is an FDA-approved nonhormonal therapy for treatment of menopause-related vasomotor symptoms (Strong recommendation).
    • Fezolinetant (Veozah) 45 mg orally once daily is FDA approved for treatment of moderate-to-severe vasomotor symptoms due to menopause.
    • Several biologically based therapies might help reduce hot flashes, but evidence is limited.
• Urogenital symptoms may be treated with hormonal and nonhormonal therapies.
  • Local estrogen therapy is recommended to alleviate symptoms associated with vaginal atrophy in women without concurrent vasomotor symptoms (Strong recommendation).
  • Systemic estrogen therapy is recommended for women with concurrent vasomotor and urogenital symptoms (Strong recommendation).
  • Nonestrogen water-based or silicone-based vaginal lubricants and moisturizers may alleviate vaginal symptoms (Strong recommendation).
• Overview of risks associated with HRT
  • long-term use of combined estrogen/progestin (HRT) has more risks than benefits in healthy postmenopausal women
  • long-term use of estrogen alone has benefits that do not outweigh risks overall
• For discontinuation of hormone replacement therapy
  • There is insufficient evidence to recommend tapering over abrupt discontinuation to prevent recurrence of symptoms (Weak recommendation).
  • Routine discontinuation of systemic estrogen at age 65 years is not recommended, as some women aged ≥ 65 years may require continued systemic therapy for management of vasomotor symptoms (Strong recommendation).