Pathophysiology of Menopause, Signs and Diagnosis

Menopause is the permanent cessation of menses for 12 months resulting from estrogen deficiency and is not associated with a pathology. The median age of menopause is 51. Most women experience vasomotor symptoms, but menopause affects many other areas of the body, such as urogenital, psychogenic, and cardiovascular.

Hormonal Changes

Menopause is a normal physiologic process in aging women in which the number of ovarian primary follicles quickly diminishes, such that there are inadequate amounts to respond to the effects of FSH. As ovaries age, their response to the pituitary gonadotropins FSH and LH decreases, initially causing a shorter follicular phase, fewer ovulations, and decreased progesterone production. During menopausal transition, double ovulation and luteal out-of-phase events occur and occasionally cause oestradiol levels to be above normal. The number of viable follicles decreases; eventually, the remaining follicles do not respond, and the ovaries produce very little estradiol. Estrogens are also produced by peripheral tissues (e.g., fat, skin) from androgens (e.g., androstenedione, testosterone).

The decline in estrogen levels leads to increased secretion of FSH and LH by the pituitary gland in a negative feedback loop. FSH levels rise more than LH levels because estrogen inhibits FSH more than LH. The elevated FSH levels stimulate the remaining follicles to produce more oestradiol, resulting in erratic fluctuations of estrogen levels during perimenopause. The decreased progesterone levels cause irregular and heavy menstrual bleeding due to unopposed estrogen stimulation of the endometrium.

Clinical Manifestations

The clinical manifestations of menopause vary widely among women and depend on several factors, such as genetics, lifestyle, health status, and previous use of hormonal contraception or therapy. The most common symptoms are vasomotor symptoms (hot flashes and night sweats), which affect about 75% of women and can last for several years. Vasomotor symptoms are caused by changes in the thermoregulatory centre in the hypothalamus due to estrogen withdrawal. They are characterized by sudden sensations of heat in the upper body, face, and neck, followed by sweating and chills. They can be triggered by stress, alcohol, caffeine, spicy foods, or warm environments.

Other symptoms of menopause include:

• Genitourinary syndrome of menopause (GSM): This syndrome refers to the symptoms and signs due to estrogen deficiency affecting the lower urinary tract and the vagina, such as vulvovaginal atrophy, dryness, itching, burning, dyspareunia (painful intercourse), urinary frequency, urgency, incontinence, and recurrent urinary tract infections.
• Psychogenic symptoms: These symptoms include mood swings, irritability, anxiety, depression, insomnia, fatigue, cognitive impairment (memory loss, difficulty concentrating), and reduced libido. They may be related to hormonal changes or psychosocial factors (stressors, life events).
• Cardiovascular effects: Estrogen has beneficial effects on the cardiovascular system by improving lipid profile (lowering LDL and raising HDL), enhancing endothelial function (vasodilation), inhibiting platelet aggregation (antithrombotic), and modulating inflammation (anti-inflammatory). The loss of estrogen increases the risk of cardiovascular disease (CVD) in postmenopausal women. CVD is the leading cause of death among women aged 50 years and older
• Skeletal effects: Estrogen plays a key role in maintaining bone mass by inhibiting osteoclast activity (bone resorption) and stimulating osteoblast activity (bone formation). The decline in estrogen levels accelerates bone loss and increases the risk of osteoporosis and fractures in postmenopausal women. Osteoporosis is a silent disease that often remains undiagnosed until a fracture occurs.

Diagnosis

The diagnosis of menopause is clinical: absence of menses for 1 year. Hormone variations are common, and it is difficult to diagnose menopause based on hormonal levels. In rare situations specialist may prescribe blood tests to check levels of FSH and estrogen

Treatment

The treatment of menopause depends on the severity of symptoms and the individual preferences of each woman. The main goals are to relieve symptoms.

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References:

 What is the menopause and what are the signs? - BBC News. (2019, May 14). Retrieved from https://www.bbc.co.uk/news/health-48258910

What Are The 34 Symptoms Of Menopause? | UK Meds. (2019, October 21). Retrieved from https://www.ukmeds.co.uk/blog/what-are-the-34-symptoms-of-menopause

Menopause - NHS. (n.d.). Retrieved from https://www.nhs.uk/conditions/menopause/