Menopause

May 12, 2021

Menopause

Menopause is a common often frustrating Women's Health condition caused by a woman's permanent cessation of her menstrual period for more than 12 consecutive months. The sudden drop in estrogen, progesterone and testosterone levels from menopause result in hot flashes, night sweats, irritability, insomnia, weight gain, stomach aches, joint pain, hip pain, vaginal dryness, painful intercourse, bladder infections, anxiety, depression and sadness.

While progesterone and testosterone begin to decline for women around age 35 as seen in Perimenopause, Menopause is primarly associated with the deficiency of estrogen hormone. Menopause typically occurs between 40 and 50 years of age, with the average age of menopause being 52 years old.

While, in the United States, studies reported that women at the age of 51 often experience menopause. Further, every year 1.3 million women report menopausal symptoms in the United States. Women with menopause lost the ability to become pregnant naturally. 

Medical studies reported that hormonal disturbances are common in the later stages of life, and the same is the case for the development of menopause. Depletion of estrogen level leads to the high concentration of follicle-stimulating hormone and luteinizing hormone in the body that significantly disrupt the hypothalamic-pituitary-ovarian axis. As a result, endometrial development failures disrupt the regular menstrual cycles and finally develop various menopausal symptoms. Moreover, different surgical procedures such as hysterectomy with bilateral oophorectomy may also cause menopause. Plus, other conditions like cancer chemotherapy and endometriosis with antiestrogens medication can also lead to the development of menopause. [1, 2]

It is important for women not to confuse Perimenopause, Menopause, and Postmenopause. These are all three different conditions. Perimenopause is characterized by irregular periods with the heavier or lighter menstrual flow before menopause. While menopause is the complete absence of menstruation, and the years after menopause are termed Postmenopause.

Signs and Symptoms of Menopause

Menopausal signs and symptoms are divided into the following three main categories. [1, 3]

Vasomotor Symptoms: Studies reported that 75% of menopausal women experience vasomotor symptoms. The vasomotor symptoms include: 

  • Migraine 
  • Hot flashes 
  • Palpitations 
  • Headache 
  • Night sweat

Hot flashes are the prominent symptoms of menopause experiencing by almost 85% of menopausal women. A menopausal hot flash episode often remains for at least three to four minutes. Moreover, different factors such as alcohol, emotional stress, and diet may aggravate hot flashes. Studies reported that the average age of menopausal hot flashes is around 5.2 years. 

Note that the intensity and severity of migraine changes over time. Studies also reported that the migraine without aura commonly occurs during menopause. Remember that although migraine with aura is less common in menopausal women and is highly associated with the risk of stroke. [3, 4]

Urogenital Symptoms

Urogenital symptoms occur in approximately 60% of menopausal women. These symptoms include:

  • Urethral atrophy
  • Vaginal atrophy
  • Sexual dysfunction (such as low libido and sex drive) 

The symptoms such vaginal dryness, pruritus, and dyspareunia (painful intercourse) results from vaginal atrophy. In contrast, urethral atrophy leads to urgency, frequent urination, dysuria, and stress incontinence. [3]

Psychological Symptoms

Around 45% of menopausal women report psychological symptoms. These symptoms include:

  • Anger
  • Irritability 
  • Anxiety
  • Stress 
  • Depression
  • Sleep disturbance
  • Poor concentration
  • Loss of self-esteem
  • Low confidence

Studies also recommend checking and evaluating the weight, blood pressure, and breast appearance evaluation during the examination of menopause. [3] 

Causes of Hot Flashes during Menopause

A hot flash is a feeling of sudden warmth in the upper body parts, experiencing high in the chest, face, and neck region. Sometimes it is accompanied by sweating, plus afterward chills. Medical research studies are still working to explore the exact causes of menopausal hot flashes. However, different studies attributed the hot flashes development to hormonal changes during menopause. Such as the fluctuations in the estrogen or progesterone level, less estrogen production, and modulation of the thermoregulatory system that results in the development of hot flashes. [3, 5]

Also, medical research studies attributed the hot flashes to the estrogen withdrawal and imbalance between estradiol and follicle-stimulating hormone levels. Moreover, studies reported the association between hot flashes and a high concentration of serotonin that triggers changes in the set-point temperature. A low estrogen level modulates the activation of serotonin receptors in the hypothalamus that change the set-point temperature sensitivity and results in hot flashes. [3, 5, 6]

Complications of Menopause

Studies reported that women with menopause are at greater risk of developing certain medical conditions. These conditions include heart and blood vessel diseases, urinary incontinence, osteoporosis, sexual problems, and weight gain. [1, 2]

Menopause Diagnosis and Tests

The diagnosis of menopause involves the evaluation of clinical symptoms and patient age. Generally, there is no need for lab tests to confirm menopause. However, in rare cases, the levels of hormones, including the follicle-stimulating hormone, thyroid-stimulating hormone, and estradiol levels, are analyzed for menopause diagnosis. [1, 2]

Menopause Treatment History

Different interventions from opium to acupuncture were used for the management of menopausal symptoms till 1942. Then Wyeth pharmaceutical introduced Premarin containing estrogen obtained from pregnant-mare urine for the treatment of menopause. And the sales of Premarin spiked until the 1970s reports, linking it with a high risk of breast cancer. During that time, the formulation was modified with the addition of progestin to ensure safety and efficacy. But the 1984 National Institutes of Health assertion backed that estrogen is an effective agent for hot flashes, bone loss prevention, night sweat, and other menopausal symptoms. [7]

Moreover, by the 1990s, the American Heart Association, the American College of Physicians, and the American College of Obstetricians and Gynecologists recommended estrogen for both heart conditions and bone loss. As a result, estrogen use soared up again among menopausal women until the Women’s Health Initiative (WHI) in July 2002. The Women’s Health Initiative (WHI) conducted a study on around 17,000 postmenopausal women. The study revealed that the combination of estrogen and progestin increased the mortalities in postmenopausal women due to increased risk of blood clotting, heart attack, stroke, breast cancer, and ovarian cancer. This report changed the whole scenario of hormone replacement therapy for more extended periods. Later, multiple research studies confirmed the WHI reports and found a high incidence of heart conditions and cancer with hormone therapy. The risk of these morbidities is prevalent in women older than 60 years. Moreover, women who abruptly stopped the hormone therapy intervention also showed a significant risk of death or comorbidities. Thus, the prescription of hormone therapy depends on the patient medical condition, duration of therapy and previous history. [7]

Present therapeutic recommendation about Hormone replacement therapy

The current studies and experts suggest the use of hormone therapy for a short period. Yes, hormones are effective and drugs of choice in the treatment of menopausal symptoms. Plus, it is advised to always consider the evaluation of family cancer history before administering hormones. Moreover, weigh the benefit-risk ratio of hormone therapy and recommend a symptomatic approach to treat menopausal symptoms. Don’t use hormones for more extended periods or during any severe medical conditions like coronary disease or cancer. [7]

Treatment of Menopause

Various treatment interventions help the management of menopausal symptoms and prevent the risk of severe medical conditions. These treatment options include:

Hormone Replacement Therapy

Hormone therapy is considered the most effective approach to treat menopausal symptoms. It helps prevent both vasomotor symptoms, urogenital symptoms, and improves lipoproteins level, and reduces the risk of osteoporosis. The hormonal agents include systemic estrogen, estrogen-progestin combination, progestin alone, estrogen-bazedoxifene combination, or progestin combined with oral contraceptives. [1-3]

Hormonal replacement therapy helps treat hot flashes, improves sleep disturbance, prevents bone loss, and helps urogenital atrophy. It is important to know that estrogen alone is not recommended in women with uterus as it can cause uterine hyperplasia and cancer in such women. It is usually recommended for menopausal women with hysterectomy. The combination of estrogen and synthetic progestin is mainly prescribed to menopausal women with an intact uterus. [1-3]

Note that always use hormonal agents for a short-term duration at their lowest therapeutic doses. Because the long-term use of hormone replacement therapy is associated with a high risk of coronary heart diseases, thromboembolism, breast cancer, stroke, and ovarian cancer. Side effects of hormones involve bleeding between periods, gastrointestinal symptoms, and breast tenderness. The [1-3]

Alternative to Oral estrogen

Medical research studies reported the following alternative to oral estrogen formulations. [3, 7]

  • Transdermal estrogen: For topical application over the skin.
  • Localized estrogen: Vaginal application for urogenital symptoms. 
  • SSRIs: Oral administration of SSRIs as antidepressant agents.
  • Localized DHEA: Vaginal application of Dehydroepiandrosterone (non-estrogenic hormone) for vaginal dryness and tissue strengthening.

Localized Estrogen Therapy

Estrogen intended for vaginal administration helps urogenital symptoms, including vaginal dryness, vaginal atrophy, intercourse discomfort, and other urinary symptoms. Different dosage forms such as creams, rings, and suppositories deliver estrogen to the vaginal tissues. The localized estrogen therapy is associated with a bit of risk of venous thromboembolism. Alternative to vaginal estrogen, hormone-free remedies, including plant oils and lubricant, are also helpful in managing vaginal dryness. [1-3]

Non-Hormonal Treatment

Non-hormonal treatment involves using antidepressants, anti-seizure, and antihypertensive agents for a short duration, usually up to a few months. The antidepressant, including both serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in low doses, helps the management of both vasomotor (hot flashes) and psychological symptoms (poor mood). Paroxetine is the only FDA-approved SSRI for the treatment of hot flashes. Besides, Gabapentin, an anti-seizure agent, also helps reduction of menopausal hot flashes. Clonidine is an antihypertensive agent that might help both high blood pressure and hot flashes during menopause. [1-3]

Selective Estrogen Receptor Modulators (SERMs)

Selective estrogen receptor agents modulate the estrogen action without interfering with the endometrial growth. These agents include raloxifene, ospemifene, and bazedoxifene that help prevention of osteoporosis and improve lipoprotein level. Also, estrogen combined with these modulators significantly helps vasomotor symptoms and prevent hot flashes. Among these modulators, the ospemifene is highly effective in the management of vaginal dryness. [1-3]

Osteoporosis

Osteoporosis-specific treatment in menopausal women involves the intervention of the administration of denosumab, bisphosphonates, and supplementation of calcium and vitamin D. Both denosumab and bisphosphonates inhibit the activity of osteoclasts and resorption of bones that increase bone density and prevent the risk of fractures. The supplementation of Vit D and calcium strengthen the bones and improve bone mineralization. [1-3]

Nonprescription Remedies

Complementary and alternative treatments include phytoestrogens, vitamin E, and omega-3 fatty acids. Vitamin E and omega-3 fatty acids have been used to treat the vasomotor symptoms of menopause. They are generally safe; however, studies have shown that they are no better than placebo. [1-3]

Certain plants contain a high concentration of plant-based estrogen, known as a phytoestrogen. These plants include soybeans, whole grains, lentils, legumes, flaxseed, chickpeas, and various fruits and vegetables. They are rich sources of the main types of phytoestrogens, including Isoflavones and Lignans. [1-3]

Role of Bioidentical hormones in the management of menopausal symptoms

Bioidentical hormones are referred to the manmade hormones obtained from plant sources that share a similar chemical structure with the human testosterone, progesterone, and estrogen hormones. Examples of bioidentical hormones include 17 beta-estradiol, estrone, progesterone, and estriol. They are available in different dosage forms, including patches, oral pills, topical gels, vaginal capsules, and topical creams. Bioidentical hormones are either made by pharmaceutical companies or by pharmacies according to a physician's order. They help treat various menopausal symptoms, including hot flashes, mood disturbances, night sweats, sleep problems, low libido, and weight gain. The bioidentical hormones made in a pharmacy, known as compounded bioidentical hormones, are not approved by FDA. They are marketed as safe and effective bioidentical hormones, but they may possess serious health risks. The side effects of bioidentical hormones include fatigue, excessive facial hair growth, bloating, mood swings, and acne. It is important to mention that FDA recommends low doses of hormone replacement therapy for short-term use. 

https://www.health.harvard.edu/newsweek/What-are-bioidentical-hormones.htm

Natural treatment of menopause

Medical research studies reported a significant positive impact of the following herb on menopausal symptoms. 

Lifestyle modifications:

Various lifestyle interventions can also ease the menopausal signs and symptoms. [3] These include:

  • Avoid consuming alcohol, smoking, hot beverages, warm weather, spicy foods, and stress.
  • Use cold fluids, light dress and spend more time or live in a cool room.
  • Avoid caffeine and other foods that disrupt the sleep cycle. Ensure a well-balanced diet. 
  • Get enough sleep, do regular exercises, including pelvic floor muscle exercise, yoga, and meditation. Also, practice other relaxation techniques such as massage, deep breathing, and guided imagery.

References

  1. Peacock K, Ketvertis KM. Menopause. [Updated 2021 Feb 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507826/
  2. Cologne, Germany: Institute for Quality and Efficiency in Health Care (IQWiG); 2006-. Menopause: Overview. [Updated 2020 Jul 2]. Available from: https://www.ncbi.nlm.nih.gov/books/NBK279311/
  3. Santoro, N., Epperson, C. N., & Mathews, S. B. (2015). Menopausal Symptoms and Their Management. Endocrinology and metabolism clinics of North America, 44(3), 497–515. https://doi.org/10.1016/j.ecl.2015.05.001
  4. Johnson, A., Roberts, L., & Elkins, G. (2019). Complementary and Alternative Medicine for Menopause. Journal of evidence-based integrative medicine, 24, 2515690X19829380. https://doi.org/10.1177/2515690X19829380
  5. Bansal, R., & Aggarwal, N. (2019). Menopausal Hot Flashes: A Concise Review. Journal of mid-life health, 10(1), 6–13. https://doi.org/10.4103/jmh.JMH_7_19
  6. Freedman R. R. (2014). Menopausal hot flashes: mechanisms, endocrinology, treatment. The Journal of steroid biochemistry and molecular biology, 142, 115–120. https://doi.org/10.1016/j.jsbmb.2013.08.010
  7. Jennifer Wolff, AARP the Magazine, “A Brief History of Treating Menopause;”How estrogen therapy got a bad name — and why doctors now say it shouldn't have”. August/September 2018. https://www.aarp.org/health/conditions-treatments/info-2018/menopause-symptoms-treatment-estrogen-hrt.html

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