Menopause

Menopause Overview

Menopause is a natural biological process characterized by the cessation of menstruation and is often associated with various physical and emotional changes. There are several commonly referenced aspects or symptoms of menopause that can be humorously termed as the "Seven Dwarves of Menopause": Itchy, Bitchy, Sweaty, Sleepy, Bloated, Forgetful, and Psycho.

Historical Context

Two centuries ago, it was uncommon for women to live long enough to experience menopause, with fewer than 30% reaching this stage. In modern times, women can expect both a better quantity and a potentially improved quality of life as they navigate menopause.

Menopausal Transition

Approximately 95% of women experience menopause between the ages of 45 and 55, with the average age being 51. Menopause is defined as the absence of menses for 12 consecutive months. It is preceded by a transitional phase known as perimenopause, which generally starts about four years before the final menstrual period and encompasses various physiological changes that can significantly affect a woman's quality of life.

Hormonal Changes

Progesterone

Progesterone levels typically undergo the first significant changes during menopause, leading to symptoms such as excessive bleeding.

Estrogen

Estrogen is a vital hormone with receptors throughout the body. Its decline during menopause can occur unevenly, resembling a roller coaster effect. Typical symptoms associated with decreased estrogen levels include:

  • Hot flushes

  • Vaginal dryness

  • Sleep disturbances
    These symptoms serve as crucial signals indicating hormonal changes within the body.

Comprehensive Symptoms of Hormonal Changes

The withdrawal of estrogen brings about several symptoms:

  • Hot flashes

  • Night sweats

  • Sleeplessness

  • Palpitations

  • Mood swings

  • Fatigue
    The lack of estrogen also leads to consequential health issues such as:

  • Cognitive decline (affecting brain function)

  • Osteoporosis (bone densitancy loss)

  • Joint tightness

  • Atherogenesis (blood vessel health deterioration)

  • Loss of libido and dryness in genitalia.

Management of Vasomotor Symptoms

Lifestyle Changes:

  • Engage in regular exercise

  • Limit intake of caffeine and alcohol

Supplements:

  • Black cohosh, soy, red clover are suggested.

Medications:
Hormone replacement therapy (HRT) is among the treatment options available.

Addressing Weight Gain

Women should:

  • Make healthier food choices

  • Take multivitamins regularly

  • Consume higher calories earlier in the day

  • Practice portion control

  • Avoid fad diets

  • Incorporate consistent exercise into their lifestyle as a permanent habit.

Abnormal Uterine Bleeding

Irregular cycles during menopause are linked to fluctuations in serum follicle-stimulating hormone (FSH). Typically, this transition is marked by reduced menstrual bleeding. However, some women may encounter heavier or prolonged bleeding due to anovulatory cycles or prolonged unopposed estrogen exposure. Notably, women with obesity or uterine fibroids are at a heightened risk of experiencing heavy bleeding.

Psychological Symptoms

Includes:

  • Mood swings

  • New onset depression

Cardiovascular Health

Post-menopausally, there is a noted average rise of about 6% in low-density lipoprotein (LDL) levels, translating into increased cardiovascular risk. However, this risk does not escalate to a point where hormone therapy poses significant cardiovascular disease risks.

Cognitive Effects

Symptoms can include:

  • Memory loss

  • Concentration difficulties
    These cognitive challenges may be exacerbated by sleep disturbances.

Loss of Libido

Libido loss can be attributed to various factors:

  • Physiological causes such as vaginal atrophy

  • Multifaceted psychological reasons
    There is generally no quick remedy for this issue, reinforcing the need for supportive therapies.

Evaluation and Diagnosis

Women over 45 displaying irregular menstrual cycles alongside menopausal symptoms likely indicate they are in transition. New endocrine disorders are relatively rare in this demographic; therefore, extensive testing like FSH evaluation may not be required and can often be misleading. It is recommended to check for TSH and prolactin levels in cases where symptoms hint at other health issues, such as galactorrhea, goiter, or tachycardia.

Understanding Perimenopause

It is crucial to remember that perimenopause is a natural life stage, not a disease. Medical intervention is not always necessary, but if the mental, physical, and emotional impacts are severe enough to hinder life quality, palliative therapy may be warranted.

Hormone Replacement Therapy (HRT)

Estrogen Considerations

Estrogen treatment for postmenopausal women helps manage symptoms but has associated risks. Specifically, using estrogen alone can elevate the risk of endometrial hyperplasia and carcinoma. Therefore, women with a uterus should receive a combined therapy of estrogen and progestin to mitigate these risks.

Using Estrogen

Estrogen is typically recommended as a short-term solution, except for individuals with specific contraindications, including:

  • History of breast cancer

  • Coronary heart disease

  • History of deep vein thrombosis (DVT) or cerebrovascular accident (CVA)

  • Active liver disease

  • Other high-risk conditions for these complications.

Benefits of Estrogen

The benefits of estrogen include:

  • Reduced symptoms of depression

  • Improved mood

  • Maintenance of skin thickness and collagen

  • Diminished osteoarthritis risks

  • Reduced risks associated with hot flashes, night sweats, vaginal dryness, sleep deprivation, and urinary issues.

Women’s Health Initiative (WHI)

The WHI study, initiated in 2002, prompted a shift in clinical practices regarding hormone therapy. Prior to this, estrogen therapy was standard; however, findings revealed significant risks associated with combined estrogen/progestin therapy, such as increased coronary heart disease events, stroke, and breast cancer. Benefits included reductions in fractures and colorectal cancer risks. Notably, adverse outcomes were not found in the group receiving unopposed estrogen.

WHI Participant Profile

Among the WHI participants:

  • 4% had a prior myocardial infarction (MI)

  • 3% had prior coronary artery bypass graft (CABG)

  • 40% were smokers

  • Others had histories of cerebrovascular accidents, DVT, or diabetes

  • The mean age was 63

  • 34% had a BMI greater than 30.

Recommendations from the North American Menopause Society

The North American Menopause Society recommends utilizing the lowest effective dose of hormone therapy for the shortest duration possible, typically no longer than five years.

Hormonal Regimens

The various hormone regimens available for managing menopause symptoms include:

  • Continuous-combined: Daily estrogen plus progesterone in a single tablet.

  • Cyclic-combined: Estrogen taken for 25 days, with a hormone-free interval of 3-6 days; progestin administered in the last 10-14 days of the cycle.

  • Continuous-cyclic: Daily estrogen coupled with progestin taken for 10-14 days each month.

  • Intermittent-combined: Daily estrogen with cycles of 3 days on/3 days off for progestin.

  • Continuous-long cycle: Daily estrogen with progestin added every 2-6 months.

Hormonal Preparations

Common preparations for hormone therapy include:

  • Oral: Premarin, Estrace

  • Transdermal patches: Climara, Vivelle

  • Vaginal rings: Estring, Femring

  • Topical sprays: Evamist

  • Creams and gels: Estrogel

Other Options for Menopausal Symptoms

Duavee

This medication combines conjugated estrogen (0.45mg) with bazedoxifene (20mg) and is indicated for treating vasomotor symptoms and osteoporosis prevention. Bazedoxifene mitigates the risk of endometrial hyperplasia typically associated with estrogen use alone. The contraindications mirror those of estrogen therapy.

Selective Estrogen Receptor Modulators (SERMs)

Osphena (Ospemifene) acts as an estrogen agonist specifically in the vagina without major estrogenic effects on the endometrium or breast tissue. It is especially effective for vulvovaginal atrophy, dyspareunia, and vaginal dryness but may cause hot flushes and has potential thrombotic side effects.

SSRIs and SNRIs

Low-dose Paxil, marketed as Brisdelle, is found to be effective, along with other medications like venlafaxine, fluoxetine, escitalopram, and desvenlafaxine. Care should be taken when prescribing to women on adjuvant tamoxifen therapy, as SSRIs can potentially diminish tamoxifen's efficacy.

Veozah (Fezolinetant)

A novel neurokinin 3 receptor antagonist (NK3R) that affects the thermoregulatory center in the hypothalamus. Two dosages (30mg and 45mg) are available and have demonstrated reductions in hot flashes and sleep disturbances. An increase in liver function tests (LFTs) occurred in 2% of subjects during trials; hence LFTs should be monitored at baseline and every 3 months for the initial nine months.

Additional Options

  • Gabapentin: Used off-label for hot flash reduction; the mechanism is still not understood.

  • Clonidine: Its use has decreased due to adverse side effects.

Nonpharmacologic Approaches

Treatment methods may encompass:

  • Meditation

  • Massage

  • Yoga

  • Regular exercise

  • Taking lukewarm baths

  • Maintaining a cool sleeping environment

  • Sustaining a healthy weight

  • Avoiding smoking and triggers that provoke symptoms.

  • The effectiveness of soy and black cohosh is variable in clinical studies.

  • Caution with herbs that may have estrogenic effects, especially if estrogen is contraindicated. Herbs include dong quai, flax seed, menerba, pine bark extract, red clover, and wild yam.

Bioidentical or Compounded Hormones

Bioidentical hormones are synthesized to be chemically identical to human hormones, often derived from soy or yams. Compounded products, created in a lab per individual specifications, have not been proven to be safer or more efficient compared to standard hormones. Notably, progesterone creams do not offer uterine lining protection and generally carry a higher cost.

Genitourinary Syndrome of Menopause (GSM)

This condition, often synonymous with vulvovaginal atrophy, can lead to:

  • Vaginal dryness

  • Burning sensation

  • Dyspareunia (painful intercourse)

  • Increased risk of urinary tract infections
    If symptoms are localized, local treatments are recommended. For systemic symptoms, a systemic approach is preferred, with first-line treatments including lubricants and moisturizers such as KY, Replens, and Vagisil. The phrase "use it or lose it" highlights that sexually active women may experience better natural lubrication.

Vaginal Estrogen Therapy

Topical estrogen is available in various forms (creams, rings, and inserts) and tends to absorb less systemically than oral forms, thereby removing the need for concurrent progestin therapy.

Prasterone

A daily suppository containing DHEA that can affect levels of circulating testosterone and estrone. It serves to treat dyspareunia and is shown to penetrate deeper vaginal tissues compared to topical estrogen, but caution is warranted for individuals with estrogen-sensitive malignancies.

Imvexxy

Introduced for treating dyspareunia due to menopause, Imvexxy is estradiol vaginal inserts approved for moderate to severe dyspareunia. Each soft gel capsule is administered intravaginally once a day for two weeks, followed by two applications weekly. The available strengths are 4mcg and 10mcg, with headache being the most frequently reported side effect. All estrogen contraindications apply.