Menopausal Symptoms and Treatment Options

Menopause is a natural phase in a woman's life, marking the end of her reproductive years. While it typically occurs around the age of 51, the journey to menopause, known as the menopausal transition or perimenopause, can begin as early as a decade before the final menstrual period. This transitional phase is characterized by a range of symptoms that can have a significant impact on a woman's quality of life. In this article, we will delve into the prevalence, impact, diagnosis, and various treatment options for menopausal symptoms.

The Prevalence and Impact of Menopausal Symptoms

Early Onset and Variability

Menopausal symptoms often make their debut during the perimenopausal period, sometimes as early as ten years before a woman experiences her last menstrual period. However, the timing can vary widely among individuals. Additionally, approximately 1.0% to 3.7% of women worldwide face premature ovarian insufficiency, leading to menopause before the age of 40. Various factors, including chromosomal abnormalities, autoimmune processes, cancer treatment, surgery, or idiopathic causes, contribute to this condition.

The Complex Nature of Symptoms

Menopausal symptoms are multifaceted and result from intricate interactions between biological, psychological, and social factors. Among these, vasomotor symptoms, such as hot flashes and night sweats, are the most commonly reported and can affect up to 80% of women. While most vasomotor symptoms tend to diminish within seven years after the final menstrual period, 25% of women may experience them for up to a decade, and 10% endure these symptoms for even longer. Furthermore, vasomotor symptoms have been linked to increased cardiovascular risk, bone loss, and heightened bone turnover.

Impact on Quality of Life

Menopausal symptoms, particularly when experienced in abundance, can lead to a significant decline in both mental and physical quality of life. The transition into menopause, regardless of symptomatology, has also been associated with reduced health-related quality of life. These symptoms can adversely affect work productivity and result in increased healthcare utilization and costs.

Diagnosis of Menopause

Age and Symptom Evaluation

For individuals aged 45 or older presenting with menopausal symptoms or amenorrhea, extensive laboratory tests and imaging studies are generally not required unless symptoms suggest alternative diagnoses. However, pregnancy should be ruled out in sexually active patients not using contraception.

Younger Patients

For women under the age of 45 with irregular or absent menstrual cycles, clinicians should order follicle-stimulating hormone (FSH) levels, though FSH levels can vary significantly during perimenopause. Additionally, endocrine disorders such as hyperprolactinemia and hypothyroidism should be ruled out as causes of secondary amenorrhea. Pregnancy should also be excluded in this group. In cases where women under 40 present with irregular cycles and menopausal symptoms, a comprehensive work-up for secondary amenorrhea, including FSH and serum estradiol, is recommended.

Atypical Symptoms

For menopausal patients experiencing vasomotor symptoms that are atypical, more frequent than expected, or associated with unusual accompanying symptoms, healthcare providers should consider alternative diagnoses such as carcinoid syndrome, pheochromocytoma, or hematologic and solid organ malignant diseases. Investigations should be conducted accordingly.

Treatment of Troubling Menopausal Symptoms

Menopausal Hormone Therapy

Leading medical societies, including the Society of Obstetricians and Gynaecologists of Canada and the North American Menopause Society, endorse menopausal hormone therapy as the primary treatment for vasomotor symptoms in both menopausal and perimenopausal patients. This therapy combines estrogen and progestin components, reducing bothersome menopausal symptoms and safeguarding the endometrium against hyperplasia and endometrial cancer. In Canada, systemic estrogens are available in various forms, including oral, transdermal patches, and gels. Progestins come in synthetic and micronized forms, administered orally, transdermally (in combination with estrogen), or via an intrauterine device.

Alternative Treatment Options

For patients who cannot or prefer not to undergo menopausal hormone therapy due to contraindications or personal preferences, alternative nonhormonal options exist. These include certain selective serotonin reuptake inhibitors (SSRIs), serotonin–norepinephrine reuptake inhibitors (SNRIs), gabapentinoids, clonidine, and oxybutynin. Gabapentinoids, when taken at night, can effectively alleviate nocturnal symptoms. Emerging options include neurokinin-3 receptor antagonists, which stabilize the temperature control center in the hypothalamus. While some herbal supplements have shown promise in improving menopausal symptoms, a detailed review of nonpharmacologic treatments is beyond the scope of this article.

Benefits and Risks of Menopausal Hormone Therapy

Benefits

Menopausal hormone therapy can significantly alleviate vasomotor symptoms, reducing them by as much as 90% in patients with moderate-to-severe hot flashes. It also improves sleep quality and mood disturbances. Evidence suggests that it may help manage genitourinary syndrome of menopause, though this can also be addressed with lubricants, moisturizers, vaginal estrogens, or oral selective estrogen receptor modulators.

Metabolic Benefits

Menopausal hormone therapy offers metabolic benefits, including improved lipid profiles (increased high-density lipoprotein and decreased low-density lipoprotein and lipoprotein [a]). Some studies even hint at enhanced insulin sensitivity and a potential reduction in diabetes risk. These benefits are more pronounced with oral estrogen therapy due to its hepatic first-pass effects.

Osteoporosis Prevention

Consistent evidence indicates that menopausal hormone therapy reduces the incidence of osteoporosis-related fractures. For instance, the Women's Health Initiative study reported a 34% reduction in hip fractures, a 34% reduction in vertebral fractures, and a 23% reduction in other osteoporotic fractures among women who took hormone therapy compared to those who did not.

Risks

While numerous studies have associated menopausal hormone therapy with an increased risk of breast cancer, it's essential to interpret these findings in the context of individual patient characteristics. For those aged 50–59 or starting treatment within the first 10 years of menopause, the additional risk of breast cancer is estimated at only 3 additional cases for every 1000 women using combined menopausal hormone therapy for 5 years. Moreover, estrogen alone appears to carry a lower risk of breast cancer than combined therapy, with synthetic progestins associated with a higher risk.

Cardiovascular and Thromboembolic Risks

Recent data suggest that the risk of cardiovascular events and thromboembolic events is primarily elevated in older patients (aged > 60 years) who initiate hormone therapy after a 10-year postmenopausal window. Younger patients (aged < 60 years) face a lower absolute risk of stroke from standard-dose hormone therapy. Transdermal estrogen formulations are associated with a reduced risk of venous thromboembolic events compared to oral treatments.

Considerations for Initiating Menopausal Hormone Therapy

For average-aged menopausal or perimenopausal patients without contraindications for menopausal hormone therapy and no specific risk factors, no single hormone regimen is preferred. When starting therapy, clinicians should consider the patient's individual disease risk, mode of delivery (oral vs. transdermal, combined vs. separate dosing), need for uterine protection, and cost. Patients with specific risk factors, such as breast cancer, should be offered individualized regimens, such as tissue selective estrogen complexes (TSECs) or estrogen alone. Similarly, those at risk for venous thromboembolic events should consider low-dose transdermal therapy.

Common Adverse Effects

Menopausal hormone therapy can lead to adverse effects like vaginal bleeding, mastalgia, and headache. Unexpected vaginal bleeding is the most frequent adverse event, and further investigations may be needed if it persists beyond 4-6 months or if risk factors for endometrial cancer are present.

In conclusion, understanding menopausal symptoms, their impact on women's lives, and the array of available treatment options is crucial for healthcare providers and patients alike. Menopausal hormone therapy remains a powerful tool for symptom management, but it should be tailored to individual patient characteristics and preferences. Nonhormonal alternatives also provide valuable options for those who cannot or choose not to pursue hormone therapy. Ultimately, the goal is to empower women to make informed decisions about their menopausal health, ensuring the best possible quality of life during this natural transition.

This comprehensive guide to menopausal symptoms and treatment options aims to provide valuable insights and empower both healthcare professionals and women going through this transformative phase in life.

Reference

CMAJ May 15, 2023 195 (19) E677-E682; DOI: https://doi.org/10.1503/cmaj.221438

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