Management of the menopause

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Chapter 13 Management of the menopause

Michael Flynn

Assessment

History

• past medical/surgical history
• family history
• oestrogen deficiency symptoms
• cigarette smoking (which changes the metabolism of oestrogen and reduces responsiveness to it)

Examination

• general, weight, blood pressure
• breast examination, pelvic examination

Investigations

• cervical cytology
• mammography and, if required, breast ultrasound
• bone density assessments
• vaginal ultrasound
• full blood examination, coagulation studies, lipid profile fasting glucose
• thyroid-stimulating hormone (TSH)

Management

The management of the menopausal woman is aimed at a full treatment regimen to optimise quality of life. The concept of risk and benefit should be fully explained. This includes management of:

• osteoporosis: prevention and treatment
• cardiovascular risk factors
• incontinence advice and treatment
• nutrition and exercise
• psychosexual dysfunction
• symptom relief of oestrogen deficiency symptoms

Oestrogen is the best short-term treatment for most symptomatic women with vasomotor symptoms. Contraindications to oestrogen therapy include history of breast cancer, coronary artery disease, thromboembolic event and stroke, or those at high risk of these complications. In women who have not had a hysterectomy, combined oestrogen and progesterone therapy is indicated.

The aim is to commence at lowest dose therapy for cessation of vasomotor symptoms. Topical vaginal oestrogen is effective in genitourinary symptoms. Testosterone therapy may be of help in some women with significant loss of libido or fatigue.

Trials

The Women’s Health Initiative (WHI)

This has been a long-term research program to address the most common causes of death, disability and quality of life in postmenopausal women. There have been many publications using these data.

Nurses Health Study

This study commenced in 1976 and expanded in 1989 with information from nurse participants in the United Kingdom. The primary focus is cancer prevention.

Million Women Study

Coordinated in Oxford, UK, women were recruited between 1996 and 2001 to investigate women’s health specifically in those over age 50. It particularly looks at hormone replacement therapy (HRT) and its effects on the breast and other aspects of health.

Within a clinical field where advice is changing as data emerge, the International Menopause Society provides consensus advice on the trials.

Cardiovascular disease and HRT

• HRT does not increase the risk in healthy women aged 50–59 and may even decrease the risk.
• It is unclear if there is an increase in stroke risk in healthy women aged 50–59, as no difference in WHI; however, increased risk was reported in the Nurses Health Study.
• The risk of venous thromboembolism is increased with HRT (less so with transdermal therapy); however, prevalence is low.

Breast disease and HRT

• After 5 years of combined oestrogen and progesterone, the increase in breast cancer is 8 cases per 10,000 women per year.
• Oestrogen-only replacement does not increase breast cancer rates up to 7 years.

Bone and HRT

• HRT is the first-line management in osteoporosis prevention and treatment in women aged 50–59.

Cognition and HRT

• Cognition benefits of HRT may depend upon age of initiation.

Current recommendations

• The main indication for HRT is to control menopausal symptoms.
• Avoid therapy of >4–5 years duration.
• HRT reduces fracture risks and is therefore appropriate for women with osteoporosis.
• HRT is not appropriate for primary or secondary cardioprotection.
• Review each patient’s management annually with risk–benefit assessment.

Osteoporosis and treatments

Definition. Osteoporosis is said to be present when there are reduced amounts of normally mineralised bone matrix relative to bone volume. This has an associated increased risk of fracture.

Prevalence. By age 75 years, 1 in 5 Australian women have had an osteoporosis-related fracture.

Affected bone

The skeleton is composed of 80% cortical bone (mainly in peripheral bones) and 20% trabecular bone (mainly in axial skeleton). Trabecular bone turns over more rapidly than cortical bone and is thus more sensitive to changes in resorption and formation.

Risk factors

• family history of osteoporosis or early menopause
• low calcium and protein intake
• lack of exercise
• smoking, alcohol, caffeine
• drug therapies: corticosteroids, gonadotrophin-releasing hormone (GnRH) analogues, antacid, diuretics
• thinness
• medical/surgical conditions
• oophorectomy, hysterectomy
• raised prolactin levels and thyroid function
• insulin-dependent diabetes, hyperparathyroidism

Bone mass

Peak bone mass is reached at between 30 and 40 years of age. Then bone mass falls by 1% per year until menopause. From menopause onwards, about 3% of bone mass is lost per year. The rate of loss decreases to perimenopausal rates 4–10 years after the menopause. Bone mass at any age is a function of:

• peak bone mass achieved
• age at which loss of bone mass commences
• rate at which bone loss proceeds

Specific high-risk patients for osteoporosis

• women who have had an oophorectomy prior to natural menopause
• women who have had a hysterectomy with ovarian conservation: a quarter of these women develop endocrine evidence of ovarian failure within 2 years of hysterectomy (the reasons for this remain unclear, but it is perhaps due to changes in blood flow to the ovary following surgery)
• women with prolonged amenorrhoea, due to raised prolactin levels or hypothalamic causes such as anorexia
• women using GnRH analogues (e.g. in the treatment of endometriosis or fibroids)
• women with coexisting medical conditions or medications (e.g. Cushing’s syndrome, use of corticosteroids, thyrotoxicosis, insulin-dependent diabetes)

Prevention and management of osteoporosis

General advice

• diet: including total food calcium of 1500 mf/day and vitamin D requirement of 800 IU/day
• exercise: 30 minutes 3 times a week has shown benefit in hip fracture rates
• stop smoking and reduce alcohol intake

Drug management

Women at high risk of osteoporosis, especially those with a recent fracture, should be evaluated for drug therapy.

Oestrogen

• effective therapy for prophylaxis of hypo-oestrogenic osteoporosis
• reduction in rate of bone mass loss to 0.75% per year
• possible modes of action

• indirect effect on bone resorption by increasing levels of calcitonin
• direct bone cell effects via oestrogen receptors on osteoblast-like cells

Bisphosphonates

These slow the rate of bone loss and enchance growth of new bone. Their mechanism of action is inhibition of osteoclast (now often first-line management).

Selective oestrogen receptor modulators (SERMs)

Raloxifen

• reduces bone loss, fracture risk and increases bone mineral density
• increases risk of thromboembolism

Calcitonin

• less efficacious than bisphosphonates or oestrogen
• acts directly on osteoclasts, which have calcitonin receptors (i.e. it directly inhibits osteoclasts)
• useful for treatment of severe bone pain associated with more severe osteoporosis
• suitable as an adjuvant treatment

Calcitriol

• is 1,25-dihydroxy-vitamin D3
• acts by enhancing absorption of calcium
• stimulates osteoclastic and osteoblastic activity by decreasing parathyroid hormone-driven bone resorption and direct stimulation of osteoblast
• should be given lower calcium diet

Monitoring of therapy

• Follow up with bone mineral density scans every 2 years.

Further reading and resources

International Menopause Society. HRT in the early menopause: scientific evidence and common perceptions. Summary of the First Global Summit on Menopause Related Issues. 2008:29-30. March

Million Women Study: www.millionwomenstudy.org

Nurses Health Study: www.channing.harvard.edu/nhs

van Kastern Y.M., Schoemaker J. Premature ovarian failure: a systemic review of therapeutic interventions to restore ovarian function and achieve pregnancy. Human Reproduction Update. 1999;5:483-492.

Women’s Health Initiative (WHI): www.nhibi.nih.gov/whi/index.html

World Health Organization (WHO). Scientific Group on Research on the menopause in the 1990s. In WHO Technical Report Series 866. WHO: Geneva; 1994.

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