Menopause and hormone replacement therapy

19.1

Introduction

Menopause is an inevitable component of ageing and encompasses the loss of ovarian reproductive function, either occurring spontaneously or secondary to other conditions. This has a significant influence in women’s quality of life and the likelihood of healthy ageing:

• 1.

  Temporal changes in health and quality of life (vasomotor symptoms (VMS), sleep disturbance, and depression).

• 2.

  Longer term changes in several health outcomes (urogenital symptoms, bone, and lipids).

• 3.

  The loss of sex hormones during ageing contributes to changes in body mass, musculoskeletal integrity, sexual dysfunction, and long-term risks of health and disease.

• 4.

  Metabolic syndrome (insulin resistance syndrome) increases in prevalence after menopause and consists of insulin resistance, abdominal obesity, dyslipidaemia, elevated blood pressure, and proinflammatory and prothrombotic states.

• 5.

  The prevalence of obesity [body mass index (BMI) of >30 kg/m ² ] is higher in postmenopausal women than in premenopausal women.

• 6.

  This is a multifactorial process consequence of reduced energy expenditure due to physical inactivity, compounded by depression, muscle atrophy, and a lower basal metabolic rate.

• 7.

  Increase of total body fat and a redistribution of body fat from the periphery to the trunk, which results in visceral adiposity. Postmenopausal women had 36% more trunk fat, 49% greater intraabdominal fat area, and 22% greater subcutaneous abdominal fat area than premenopausal women in studies where computed tomography and magnetic resonance imaging have been used.

19.2

Oestrogens and menopausal obesity

• 1.

  Recent studies with oestrogen receptors (ER) knockout mice have helped to unravel the role of the ERs in brain degeneration, osteoporosis, cardiovascular diseases (CVDs), and obesity.

• 2.

  Sex hormones help integrate metabolic interaction among major organs that are essential for metabolically intensive activities such as reproduction and metabolic function.

• 3.

  Sex steroids are also required to regulate adipocytes’ metabolism and also influence the sex specific remodelling of particular adipose depots.

• 4.

  The function of oestrogens is mediated by nuclear receptors (ER α and ER β) that are transcription factors that belong to the superfamily of nuclear receptors. ER α and ER β are expressed by human subcutaneous and visceral adipose tissue, whereas only ER α mRNA has been identified in brown adipose tissue.

• 5.

  ER α plays a major role in the activity of adipocytes and sexual dimorphism of fat distribution. Polymorphism of ER α in humans is associated with risk factors for cardiovascular disease.

• 6.

  Body weight and BMI were significantly higher in perimenopausal and postmenopausal than in premenopausal women.

• 7.

  SWAN cross-sectional analysis showed no correlation between obesity and age at natural menopause, but obesity was associated with a likelihood of surgical menopause.

• 8.

  Concentrations of sex hormones partially control fat distribution: men have less total body fat but more central/intraabdominal adipose tissue, whereas women tend to have more total fat in gluteal/femoral and subcutaneous depots.

• 9.

  Fat tissue and regional fat tissue as a percentage of total fat tissue were higher in the trunk and arms in perimenopausal and postmenopausal than in premenopausal women. The shift to a central, android fat distribution can be counteracted by HRT.

• 10.

  The mean oestradiol level E2 change in transition from premenopausal to postmenopausal was less pronounced in obese women when compared with nonobese women. Obese women had lower premenopausal mean E2 levels but higher postmenopausal mean E2 levels.

• 11.

  Large observational studies have reported that obesity is a key factor for perimenopausal VMS but not postmenopausal VMS.

• 12.

  Data from WHI have shown that obesity is an important correlate for multiple urogenital symptoms, and obese women were twice as likely to report severe vaginal discharge and almost four times more likely to report severe itching/irritation compared with low, normal-weight women, controlling for diabetes.

• 13.

  It has been hypothesised that adipose tissue functions as an insulator and interferes with normal thermoregulatory mechanisms of heat dissipation.

• 14.

  A study using computed tomography demonstrated an increase in subcutaneous adipose tissue with age with age, independent of menopausal status, whereas visceral and total body fat increased only in women who became postmenopausal during the 4 years of follow-up. The change in visceral obesity was accompanied by a decrease in visceral circulating oestradiol and increase in FSH.

• 15.

  Ultrasound scanning has shown no difference in antral follicle count between obese and nonobese women in late reproductive age.

• 16.

  Follicular dysfunction and alterations in central nervous system regulation of hormonal levels among obese women may be contributory factors.

• 17.

  Change occurs in the primary source of circulating E2 as the menopause transition progresses; the primary source of circulating E2 premenopausally is the ovary, whereas in postmenopause the primary source of circulating E2 is the aromatisation of androgens within the adipose tissue.