What is menopause?

Understanding Menopause

Menopause is defined as 12 consecutive months without menstruation, with natural menopause occurring at a median age of 51 years in the United States (normal range 40-60 years). 1

Definition and Diagnosis

Menopause can be diagnosed through several criteria:

• Age ≥ 60 years
• Amenorrhea for ≥ 12 months in the absence of chemotherapy, tamoxifen, or ovarian suppression
• FSH levels > 40 IU/L and estradiol levels < 30 pg/mL
• Prior bilateral oophorectomy 2, 1

For women under 60 years taking tamoxifen or toremifene, FSH and plasma estradiol levels in the postmenopausal range are required for diagnosis 2.

Physiological Changes

The menopause transition is characterized by:

• Declining ovarian follicle numbers leading to decreased inhibin B production 3
• Rising FSH levels, often beginning years before clinical symptoms appear
• Estradiol levels that remain relatively stable until late perimenopause
• Profound drop in estradiol over a 3-4 year period around final menses 3
• Testosterone levels that may remain stable or even rise after menopause
• Decline in DHEA and DHEAS with age 3

Symptoms and Health Effects

Menopausal symptoms can significantly impact quality of life and include:

• Vasomotor symptoms: Hot flashes/night sweats (occurring in 46-73% of women) 2
• Urogenital symptoms: Vaginal dryness (51%), dyspareunia (39%) 2
• Psychological symptoms: Sleep disturbances, mood changes, cognitive dysfunction
• Physical symptoms: Arthralgias/myalgias, fatigue 2, 4

Long-term health effects include:

• Bone health: Accelerated bone loss (2% per year during first 5 years after menopause, followed by approximately 1% annual loss) 1
• Cardiovascular risk: Early menopause (before age 45) and premature menopause (before age 40) are associated with increased cardiovascular disease risk 1
• Cognitive effects: Potential impact on cognitive function 1

Management Options

Hormone Replacement Therapy (HRT)

For women with bothersome menopausal symptoms, HRT is the most effective treatment option:

• Estrogen options: 17β-estradiol 1-2 mg daily (oral) or 50-100 μg/24h (transdermal) 1
• Progesterone addition: Natural micronized progesterone 200 mg for 12-14 days per month in a sequential regimen for women with an intact uterus 1
• Route considerations: Transdermal estrogen has a lower thromboembolism risk than oral formulations 1

Benefits and Risks of HRT

Benefits:

• Prevention of bone loss and reduction of fracture risk 1, 5
• Relief of vasomotor symptoms
• Potential improvement in cognitive function when started early in menopause 1

Risks:

• Combined estrogen-progesterone therapy carries a small increased risk of breast cancer 1, 5
• Increased risk of venous thromboembolism, stroke, and pulmonary embolism 5
• Potential increased risk of dementia when started in women over 65 years 5

Contraindications to HRT

HRT should not be used in women with:

• History of breast cancer
• Venous thromboembolism
• Stroke
• Coronary heart disease 1

Non-Hormonal Options

For women who cannot or choose not to use HRT:

• SSRIs/SNRIs for vasomotor symptoms and mood changes (with caution when using certain SSRIs with tamoxifen) 1
• Low-dose intravaginal estrogens for vulvovaginal symptoms 1

Special Considerations

Premature Menopause

Women experiencing premature menopause (before age 40):

• Have a 55% increased risk of nonfatal cardiovascular disease 1
• Require careful cardiovascular risk assessment 1
• May benefit from HRT until the average age of natural menopause to reduce these risks

Bone Health Management

• DEXA scan recommended to establish baseline bone mineral density 1
• Regular weight-bearing and resistance exercise 1
• Adequate calcium and vitamin D supplementation 1
• Smoking cessation and reduced alcohol intake 1

Cancer Survivors

Many cancer survivors experience menopausal symptoms without meeting the definition of menopause, particularly those on aromatase inhibitors, with history of oophorectomy or chemotherapy, or males on androgen deprivation therapy 2.

Management should be tailored based on cancer type and treatment history, with careful consideration of HRT risks in hormone-sensitive cancers.