Menopause

Written by Dr Dalene Barnard. Information adapted from UpToDate

Natural menopause is defined as the permanent cessation of menstrual periods, determined retrospectively after a woman has experienced 12 months of amenorrhea without any other obvious pathological or physiological cause. It occurs as ovarian follicles are near depleted. The age varies but occur at a median age of 52,4 years. Menopause before age 40 is termed primary ovarian insufficiency and is abnormal.

Menopause is preceded by perimenopause (or menopausal transition). This is embodied by a myriad of endocrine changes heralded by fluctuating hormone levels.

Symptoms of perimenopause

1. Menstrual irregularity.
2. Vasomotor symptoms (Hot flushes). Occur in 80% of women.
3. Vaginal dryness. Generally, worsens as menopausal years progress
4. Sleep disturbances: these are both due to changes in hormonal milieu, profoundly affecting the brain, as well as due to flushes and mood disturbances. Other factors playing a role are restless legs, sleep apnoea and partner factors such as snoring.
5. New onset depression of anxiety: the risk is 2,5 x higher in the perimenopausal years.
6. Cognitive changes such as memory loss and poor concentration. This is at its worse during menopausal transition. Oestrogen certainly improves cognitive function. Without hormone therapy cognitive function does return to normal once the hormonal fluctuation of menopausal transition is reached.
7. Accelerated bone loss
8. Increase in cardiovascular risk.

Long term consequences of oestrogen deficiency:

1. Bone loss
2. Cardiovascular disease
3. Dementia
4. Osteoarthritis
5. Body composition: women who do not take oestrogen therapy usually gain fat mass and lose lean mass
6. Skin changes: reduced collagen content of skin and bones. Skin collagen reduces wrinkling and aging of skin.
7. Impaired balance which is presumed to be an effect of central oestrogen deficit

Approach to women according to age and reproductive stage

Women younger than 40: symptoms of menopause in this age group needs a full workup including FSH, TSH, betaHCG and prolactin. If FSHis above 30 mIU/ml it confirms premature ovarian failure and this patient requires referral for causative work-up and management.

Ages 40 to 45 years: irregular menstrual cycles in this age group requires the same workup as above. If the bleeding is heavy of prolonged (>7days) a pelvic ultra sound and endometrial biopsy is indicated.

Age 45 and above: this is the time when health implications of hypooestrogenemia start. It is good to do a risk assessment for breast cancer and cardiovascular disease at this stage. I usually also do a pap smear, breast exam, bone mineral density scan and mammogram. In this group it is important to determine how long a woman has been menopausal. The Women’s Health Initiative (WHI) found that women who start menopausal hormone therapy (MHT) more than 10 years after menopause, have increased cardiovascular risk.

Menopausal hormone therapy (MHT)

MHT is given to treat the effects of hypooestrogenemia such as hot flashes and decreased bone mineral density. Other symptoms associated with perimenopause and menopause that respond to oestrogen include sleep disturbances, mood lability/depression, and, in some cases, joint aches and pains.

Route — Oestrogen is available as oral, transdermal, topical gel. Preparations. All are effective in relieving menopausal symptoms. The choice of route is determined by the side effect profile and patient preference. Transdermal oestrogen is preferred in women with hypertriglyceridemia, active gallbladder disease, known thrombophilias and migraine with aura. Oral oestrogen poses a higher risk of venous thromboembolic events (VTE), though the absolute risk in otherwise healthy women is still low. Oral oestrogen is more favourable on lipid profile, other than triglycerides (increases HDL and decreases LDL)

A good starting dose of 17-beta oestradiol is 1mg/day orally or 0,05mg/day transdermally. There is some individual variation and a woman may require a higher dose to be symptom free. Lower doses are linked with less vaginal bleeding, breast tenderness [10], fewer effects on coagulation and a possible lower risk of stroke and VTE.

If a woman still has a uterus it is imperative to add a progestogen to protect the endometrium from hyperplasia and carcinoma. Progestogens do however increase the risk of side effects and has no other benefit thus should not be given to women without a uterus. If the side-effects of systemic progestogens are not favourable, an intrauterine levonorgestrel device is an excellent option. Different progestogens have different side effects, and this can be changed if a woman finds the side effects bothersome.

Side effects

1. Breast tenderness (related to oestrogen dose)
2. Mood symptoms (related to type of progestogen)
3. Bloating (related to type of progestogen)
4. Vaginal bleeding (common in combined preparations in the first 6 months)

Tibolone (Livifem) is a selective oestrogen receptor modulator (SERM) that has been widely used in South Africa and abroad. Its metabolites have estrogenic, androgenic and progestogenic properties. It can be used with or without a uterus in situ. It has the same benefit as other MHT agents though may be slightly less effective for hot flushes. It has the advantage of improving a women’s libido due to the androgenic effects and therefore is favoured by many. It may increase the risk of strokes in women older than 60.

Contraception

Women in the perimenopausal group may still ovulate and contraception in this group is important. MHT does not suppress ovulation. Options include barrier methods, sterilisation or vasectomy, intrauterine devices, and low dose oral contraceptive. Oral contraceptive may only be given if a woman is in perfect health and is low risk for VTE. Thus, normal BMI, not smoking, exercising regularly and no history of VTE.

Before starting MHT

It is advised that you calculate a women’s cardiovascular risk and breast cancer risk prior to starting MHT. See images from UpToDate below. (For risk calculators see bcrisktool.cancer.gov/ and www.cvriskcalculator.com/)

Tables from UpToDate

Contraindications to MHT

• Personal history of breast cancer
• Coronary heart disease
• Previous VTE or stroke
• Transient ischemic attack
• Active liver disease
• Unexplained vaginal bleeding
• High-risk endometrial cancer

 Vaginal atrophy. The oestrogen dose from systemic oestrogen is usually not sufficient to maintain vaginal health. Topical oestrogen is added for complaints of vaginal dryness of dyspareunia. If systemic oestrogen is contraindicated or not preferred topical oestrogen can still be used.

Duration of use: the risk of breast cancer does increase with duration of use of MHT. It is therefore prudent to attempt to discontinue after 5 years. However, for most women experience hot flashes as long as 20 years into menopause. Reinitiating is then individualized but certainly frequently done as the benefits on quality of life and detrimental effects of hypooestrogenemia often weigh heavier than the risk of breast cancer. With extended use of MHT, aim to use the lowest effective dose.

References available on request.