Aetiology

Women are born with a set number of oocytes. As this supply of oocytes becomes depleted during their early 40s, ovarian production of progesterone, estradiol, and testosterone begins to decline. Fertility also significantly declines.

Before the menopause, estradiol is the predominant oestrogen. Serum estradiol levels vary throughout the menstrual cycle but average about 367 picomol/L (100 picograms/mL). After the menopause, oestrone, which is derived from estradiol metabolism in the liver and peripheral conversion of androstenedione in adipose tissue, becomes the dominant oestrogen. Serum oestrone levels average about 110 to 184 picomol/L (30-50 picograms/mL). Symptoms of the menopause, such as hot flushes and urogenital atrophy, are closely related to decreasing estradiol levels.[5]

Pathophysiology

The menopausal state has a number of different pathognomonic signs and symptoms, each of which is tied to decreasing ovarian hormone production.

The precise pathophysiology of vasomotor symptoms is currently unknown. The combination of biochemical changes in hormone levels, alterations in the central thermoregulatory zone, alterations in several neurotransmitter systems (serotonergic, noradrenergic, opioid, adrenal, and autonomic), genetic predisposition, and social or cultural factors all contribute to an individual’s perception and complaint of hot flushes.

Declining estradiol levels are associated with symptomatic urogenital atrophy in about 40% of postmenopausal women.[6] There may be vaginal epithelial thinning, decreased secretions, reduction in vaginal elasticity, and increase in the pH of vaginal fluid (>6). Vaginal symptoms include dryness, itching, discharge, and painful intercourse. Thinning of the vaginal and vulvar epithelium can lead to tears and bleeding with intercourse. Changes visible on examination include pallor, loss of rugae, shrinkage of the clitoris and labia minora, loss of fat padding in the labia majora, and shrinkage of the vagina. These factors can lead to significant dyspareunia with attendant declines in self-esteem, quality of life, and sexual function.

In the menopause transition, bone resorption accelerates, resulting in an average decline in bone density of 10% to 12% in the spine and hip.[7] This, combined with other factors such as deconditioning and corticosteroid use, increases the risk of fractures with activities of daily living or falls.[8]

The risk of mortality from cardiovascular disease increases with the onset of menopause, regardless of the reason for menopause onset.[9] This is primarily driven by changes associated with ageing, including increase in fat mass, insulin resistance, and modified lipid profile, with an increase in low-density lipoprotein and triglycerides and a decrease in high-density lipoprotein.[10][11]

Classification

Terminology

Menopause:

  • In healthy women, the menopause is a natural event that usually occurs between 40 and 60 years of age (average 51 years).[2]​ This represents the permanent cessation of menstruation and ovulatory function.

Premature menopause:

  • Menopause before the age of 40 years is considered premature and may occur spontaneously or because of surgery (such as bilateral oophorectomy), radiation of the pelvis, chemotherapy, autoimmune disease, fragile X syndrome, or unknown causes (idiopathic).

Premature ovarian insufficiency:

  • Refers to amenorrhoea, hypo-oestrogenic status, and elevated gonadotrophins due to a decline of ovarian function before the age of 40.

Perimenopause:

  • The transition from cyclic menstrual bleeding to a total cessation of menses may happen over several years; duration is variable. Perimenopause is marked by menstrual irregularity and periods of amenorrhoea due to declining progesterone and estradiol levels, and ends 12 months after the final menstrual period.

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