What are the signs, symptoms, diagnostic tests, and management options for a patient entering menopause?

Menopause: Signs, Symptoms, Diagnosis, and Management

Signs and Symptoms

Menopausal symptoms are diverse and affect multiple organ systems, with vasomotor symptoms (hot flashes/night sweats) occurring in 50-75% of women and genitourinary symptoms affecting more than 50% of women. 1, 2

Vasomotor Symptoms

• Hot flashes and night sweats occur in approximately 46-73% of women 3, 1
• These symptoms typically last more than 7 years and can persist for over a decade 1, 2
• Night sweats can cause significant sleep disruption 3

Genitourinary Symptoms (GSM)

• Vaginal dryness affects approximately 51% of women 3
• Dyspareunia (painful intercourse) occurs in 39% of women 3
• Urinary complaints are common 3
• These symptoms tend to be progressive and often chronic 1

Additional Symptoms

• Sexual dysfunction and decreased sexual desire 3
• Sleep disturbance 3
• Mood disturbance and depression 3
• Cognitive dysfunction 3
• Arthralgias/myalgias and fatigue 3

Diagnostic Criteria and Testing

Menopause is clinically diagnosed after 12 months of amenorrhea without another pathological cause, and laboratory testing is only indicated when the diagnosis is uncertain or in specific clinical scenarios. 3, 4

Clinical Definition

The following criteria establish menopausal status 3:

• Prior bilateral oophorectomy
• Age ≥ 60 years
• Age < 60 years with amenorrhea ≥ 12 months in the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression AND FSH and estradiol in postmenopausal range
• If taking tamoxifen or toremifene and age < 60 years, then FSH and plasma estradiol level in postmenopausal ranges

Laboratory Evaluation

Laboratory testing should include estradiol, FSH, LH, and prolactin as clinically indicated, but FSH alone is not reliable in certain populations. 3

Key testing considerations 3:

• FSH is NOT a reliable marker in women with prior chemotherapy, pelvic radiation, or those on tamoxifen
• Serial estradiol levels are useful for women who become amenorrheic and later develop bleeding to determine return of ovarian function
• Anti-Müllerian hormone (AMH) and inhibin may provide additional information but alone are not reliable to ensure menopausal status
• Rule out other medical causes: thyroid disease and diabetes should be assessed 3

Physical Examination

• Pelvic evaluation should be performed for women with vaginal dryness complaints to assess for vaginal atrophy 3

Management

First-Line Treatment Approach

Nonhormonal pharmacologic options are preferred as first-line therapy for menopausal symptoms, though hormonal therapies remain the most effective treatment and can be used after considering individual risks and benefits. 3

Nonhormonal Pharmacologic Treatment for Hot Flashes

For vasomotor symptoms, SSRIs/SNRIs reduce frequency by approximately 40-65%, while gabapentin and certain antihypertensives are also effective options. 3, 1

Specific agents 3, 1:

• Paroxetine: 7.5 mg daily reduces frequency and severity of vasomotor symptoms and nighttime awakenings
• Other SSRIs/SNRIs: Citalopram, desvenlafaxine, escitalopram, venlafaxine
• Anticonvulsants: Gabapentin
• Neuropathic pain relievers
• Certain antihypertensives

Critical caveat: Pure SSRIs, particularly paroxetine, should be used with caution in women taking tamoxifen due to CYP2D6 inhibition, though evidence on clinical impact is conflicting 3. Alternative therapy is recommended if available.

Hormonal Therapy

Menopausal hormone therapy (MHT) is the most effective treatment for vasomotor symptoms, reducing frequency by approximately 75%, but requires careful patient selection due to specific contraindications. 3, 1

Formulation Selection 3:

• Combination estrogen and progestin for women with intact uterus
• Estrogen alone for women without a uterus
• Oral and transdermal estrogen have similar efficacy 1
• Specialist management of MHT dosing is recommended 3

Absolute Contraindications 3:

• History of hormone-related cancers
• History of abnormal vaginal bleeding
• Active or recent history of pregnancy
• Active liver disease

Risk Profile

Based on WHI data with conjugated equine estrogens (CEE) ± medroxyprogesterone acetate (MPA) 5, 1:

• Increased risk of stroke and venous thromboembolism: approximately 1 excess event per 1000 person-years
• Increased breast cancer risk with CEE plus MPA: approximately 1 excess event per 1000 person-years
• Low-dose CEE plus bazedoxifene shows no increased breast cancer risk (0.25%/year vs 0.23%/year with placebo) 1

Important note: Custom-compounded bioidentical hormones are NOT supported by data showing they are safer or more effective than standard hormone therapies 3.

Treatment for Genitourinary Symptoms (GSM)

Low-dose vaginal estrogen is first-line for GSM, with subjective improvement in symptom severity by 60-80%. 1

Treatment options 3, 1:

• Local estrogen treatments: Vaginal rings, suppositories, creams (60-80% improvement)
• Vaginal prasterone: 40-80% improvement in severity
• Oral ospemifene: 30-50% improvement in severity
• Specialist referral should be considered for management 3

Special Populations

For young women experiencing early menopause, oral contraceptives may be considered for symptom relief. 3

Women with therapy-induced amenorrhea after chemotherapy: Amenorrhea is not a reliable indicator of menopausal status; oophorectomy or serial FSH/estradiol measurements are needed if aromatase inhibitors are considered 3.

Treatment Duration and Monitoring

Doses of antidepressants for vasomotor symptoms are typically much lower than those needed for depression, and response is usually evident within weeks. 3

For hormonal therapy: The timing of initiation relative to menopause onset affects the overall risk-benefit profile, with women aged 50-59 years showing more favorable outcomes 5.