Menopause and its Impact on Health

Menopause is defined as the time a woman has experienced 12 months of amenorrhea, and hence, permanent cessation of menstrual cycles. Natural menopause, occurring at a median age of 51.4 years, results from the depletion of ovarian follicular activity. This depletion reflects physiologically with decrease in hormone production by the ovaries, resulting in low estrogen levels, and counteractively, high follicle-stimulating hormone concentrations.

Although natural menopause is an inevitable biological process, other causes can be attributed to the inception of menopause, including primary ovarian insufficiency, surgical menopause, and chemotherapy and radiation therapy. Firstly, primary ovarian insufficiency (POI), previously referred to as “premature menopause” and “premature ovarian failure”, is a hypergonadotropic hypogonadism pathology causing menopause before the age of 40 years. POI is associated with diminished ovarian response to gonadotropin despite regular ovulatory menstrual cycles; however, as a spectrum disorder, POI patients can occasionally ovulate, and in 5-10% of cases, even conceive. In overt POI, the fully developed form, patients present with oligomenorrhea or amenorrhea have symptoms of estrogen deficiency, and menopausal-ranged gonadotropin levels.

Secondly, patients who have had bilateral oophorectomy have immediate menopause, with the sudden drop in hormone levels causing severe menopausal symptoms. Patients with hysterectomy, but ovarian conservation, however, can ovulate and release estrogen and progesterone, resulting in amenorrhea, but lack of immediate menopausal symptoms. Lastly, anticancer drug and radiation therapy, known ovarian toxins, induce menopause through their effect on granulosa and theca cell division more than nondividing oocytes. This causes, in extreme cases, primary hypogonadism, and in less extreme cases, return of fertility after months to years of therapy cessation.

Symptoms

Clinical manifestation of menopause usually starts with menstrual transition, also known as perimenopause, commencing usually four years prior to the final menstrual period (FMP). Progression of ovarian follicular diminution results in irregular menstrual cycles, hot flashes (most common), mood fluctuations, sleep disruptions, and vaginal dryness, as a result of hormonal fluctuation. The transition is further divided into early and late transition in accordance to the Stages of Reproductive Aging Workshop (STRAW) staging system (Fig. 1), with early transition being defined as lengthening intermenstrual interval, followed by occasional amenorrhea, skipped cycles, and anovulatory cycles during the late transition. Subsequent cessation of menstrual cycles follows years of menstrual irregularity in women, and is called postmenopause, or clinical menopause, after 12 months of amenorrhea.

In the current scenario of Nepal, a descriptive cross-sectional study was conducted among 2000 women aged over 40 years to identify their knowledge, attitude, and practice related to menopausal health problems. The study revealed that 820 (41%) women had reached menopause. The average age of menopause was 48.7 years. Majority of the women, 1183 (59.2%), did not know about menopausal health problems. Abnormal bleeding, 353 (17.65%), sweating, 315 (15.75%), hot flushes, 299 (14.95%), joint/muscle pain, 285 (14.25%), were the most common menopausal symptoms known by the women. Joint pain, 736 (36.8%), hot flushes, 584 (29.2%), irregular bleeding, 582 (29.1%), were the most common experienced symptoms of menopause, and only 586 (29.3%) consulted the health workers to alleviate menopausal symptoms. Moreover, most of the women, 926 (46.3%), accepted menopause as a part of life.

Short term symptoms

Vasomotor symptoms

Also known as hot flashes, this is the most common symptom, presenting with a sensation of heat originating from the upper chest or face and radiating to the whole body. This symptom results from estrogen withdrawal, inducing thermoregulatory dysfunction in the hypothalamus. Hot flashes are often accompanied by palpitation, perspiration, and occasionally, anxiety. Usually occurring several times per day, hot flashes are particularly common at night.

Sleep disturbance

As a result of the nocturnal nature of hot flashes, women can often experience sleep disturbance. However, studies have reported other contributing factors, as well, from anxiety to depression to primary sleep disorder to sleep apnea to restless leg syndrome. Hence, although the treatment of vasomotor symptoms may decrease sleep disturbance, it is not to say that all sleep problems will be resolved.

Depression

An increased risk of new-onset depression during perimenopause has been accounted for in various studies, with the risk decreasing in early postmenopause. Treatment of depression is discussed in the section, Hormone Replacement Therapy.

Cognitive changes

With regard to cognitive function, although memory loss and difficulty in concentration have been symptoms noted by menopausal women, the SWAN study has observed an increase in anxiety and depression to be independent, unfavorable effects on cognitive performance. Study on the association between estrogen and cognitive function has not been well-documented.

Joint pain

Although joint pains are more common in women who are obese or depressed, there is a pronounced association between this symptom and menopausal status of women. Women’s Health Initiative (WHI) clearly shows women getting relief from joint pain with either combined estrogen-progestin therapy or unopposed estrogen than with placebo, despite lack of clarity on estrogen deficiency or rheumatologic disorder as the main cause.

Urogenital symptoms

Urogenital symptoms, particularly vaginal dryness, often accompanied with itching and

dyspareunia, ensue as a result of vaginal atrophy, attributable to estrogen-deficiency-led thinning of vaginal epithelium. On inspection, the vagina appears pale, with absence of normal rugae, and external genitalia show diminished elasticity and turgor of the vulvar skin, introital narrowing, fusion or resorption of the labia minora, and scarce pubic hair. As a result of ongoing hypoestrogenism, these symptoms (sexual dysfunction, breast pain, menstrual migraines) progressively worsen with time.

Long-term consequences

Menopause results from ovarian follicular depletion, subsequently causing absence of ovarian estradiol production and secretion; yet, continuing testosterone secretion. The resultant estrogen deficiency gives way to long-term effects, from cardiovascular disease to dementia to osteoporosis.

Cardiovascular disease

An association between increased risk of cardiovascular disease and menopause has been accounted for by multiple studies, reporting the probable cause as hormonal influence on lipid profiles. To elaborate, during the menopausal transition, increase in serum low-density lipoprotein (LDL) was noted, and a decrease in the protective effect of serum high-density lipoprotein (HDL) was suggested.

Dementia

Menopausal transition can often precipitate cognitive changes as memory loss, difficulty with word retrieval, and “brain fog”. Although there is lack of evidence to associate estrogen with these cognitive changes, a cross-sectional study reports that in early midlife, women appear to outperform men on memory tasks, but with the onset of menopause and decline in serum estradiol, any memory advantage diminishes.

Osteoporosis

Commencing during menopausal transition, loss of bone mineral density is attributed to an unstable increase in the bone remodeling rate, increase in osteoclast and osteoblast numbers, and increase in resorption and formation. The highest rate of bone loss is reportedly during the one year before the FMP through two years after.

 

Postmenopausal bleeding

Postmenopausal uterine bleeding (PMB) refers to uterine bleeding in a menopausal woman, apart from bleeding in a woman taking HT. While most common causes for PMB, at best, include endometrial atrophy and endometrial polyps, at worst, it can be due to endometrial carcinoma. The crux of the matter is to diagnostically evaluate patients with PMB to rule out malignancy, with initial tests, including endometrial biopsy or transvaginal ultrasound to do so. As a result, once cancer has been excluded, no additional treatment is necessary, as most PMB is light and self-limited. However, consultation with a doctor for further evaluation is highly recommended for patients with recurrent bleeding.

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