Which adverse effect can be seen in a female client with gonadotropin deficiency and who is undergoing hormone replacement?

Menopause marks the end of menstruation in a woman’s life. It occurs because a woman stops ovulating (releasing a mature egg once monthly), and her ovaries no longer produce oestrogen (one of the female sex hormones). 

Menopause means ‘the last period’. It is a natural event that marks the end of the reproductive years, just as the first menstrual period during puberty marks the start.

Many women, although not all, experience uncomfortable symptoms before and after menopause, including hot flushes, night sweats, sleep disturbance and vaginal dryness. These symptoms and physical changes can be managed in various ways, including lifestyle changes such as healthier eating and increased exercise, and by hormone replacement therapy (HRT).

Hormone replacement therapy (HRT)

HRT, also known as hormone therapy (HT) or menopausal hormone therapy (MHT), is medication containing the hormones that a woman’s body stops producing after menopause. HRT is used to treat menopausal symptoms.

While HRT reduces the likelihood of some debilitating diseases such as osteoporosis, colorectal (bowel) cancer and heart disease, it may increase the chances of developing a blood clot (when given in tablet form) or breast cancer (when some types are used long-term).

‘Premature menopause’ is when the final menstrual period occurs before a woman is 40. ‘Early menopause’ is when the final menstrual period occurs before a woman is 45. For women who experience premature or early menopause, HRT is strongly recommended until the average age of menopause (around 51 years), unless there is a particular reason for a woman not to take it.

Menopause symptoms and HRT

Menopause symptoms that may be relieved by HRT include:

• hot flushes and night sweats
• vaginal dryness
• thinning of vaginal walls
• vaginal and bladder infections
• mild urinary incontinence
• aches and pains
• insomnia and sleep disturbance
• cognitive changes, such as memory loss
• reduced sex drive
• mood disturbance
• abnormal sensations, such as ‘prickling’ or ‘crawling’ under the skin
• palpitations
• hair loss or abnormal hair growth
• dry and itchy eyes.

Other therapies, including vaginal oestrogen products, antidepressants or other medications, may be used depending on the symptoms and risk factors. Seek advice from your doctor.

Added benefits of HRT

HRT reduces the risk of various chronic conditions that can affect postmenopausal women, including:

• diabetes – taking HRT around the time of menopause reduces a woman’s risk of developing diabetes
• osteoporosis – HRT prevents further bone density loss, preserving bone integrity and reducing the risk of fractures, but it is not usually recommended as the first choice of treatment for osteoporosis, except in younger postmenopausal women (under the age of 60)
• bowel cancer – HRT slightly reduces the risk of colorectal cancer (bowel cancer)
• cardiovascular disease – HRT has been shown to reduce cardiovascular disease markers when used around the time of menopause.

HRT needs to be prescribed for each woman individually. Some women experience side effects during the early stages of treatment, depending on the type and dose of HRT. These side effects will usually settle within the first few months of treatment and may include:

• breakthrough bleeding
• breast tenderness
• bloating
• nausea.

While HRT/MHT reduces the risk of some debilitating diseases, it may increase the risk of others. These small risks must be balanced against the benefits of HRT for the individual woman. Talk to your doctor about any concerns you may have.

Breast cancer and HRT

Women over 50 years of age who use combined oestrogen and progestogen (progesterone) replacement for less than five years have little or no increased risk of breast cancer. Women who use combined HRT for more than five years have a slightly increased risk. Women on oestrogen alone have no increased risk up to 15 years of usage.

There is no evidence to suggest that a woman with a family history of breast cancer will have an added increased risk of developing breast cancer if she uses HRT. The risk with combined oestrogen and progestogen is greater than with oestrogen alone, or with newer HRT agents such as tibolone (sold as Livial or Xyvion), and may also depend on the type of progestogen used. Studies suggest that medroxyprogesterone acetate and norethisterone have higher risks than dydrogesterone and progesterone.

Cardiovascular disease and HRT

Women over 60 have a small increased risk of developing  heart disease or stroke on combined oral (tablet) HRT. Although the increase in risk is small, it needs to be considered when starting HRT, as the risk occurs early in treatment and persists with time.

Oestrogen used on its own increases the risk of stroke further if taken in tablet form, but not if using a skin patch. Similarly, tibolone increases the risk of stroke in women from their mid-60s.

Women who commence HRT around the typical time of menopause have lower risks of cardiovascular disease than women aged 60 or more.

Venous thrombosis and HRT

Venous thromboses are blood clots that form inside veins. Women under 50 years of age, and women aged 50 to 60, face an increased risk of venous thrombosis if they take oral HRT. The increase in risk seems to be highest in the first year or two of therapy and in women who already have a high risk of blood clots. This especially applies to women who have a genetic predisposition to developing thrombosis, who would normally not be advised to use HRT.

Limited research to date suggests the increased risk of clots is mainly related to combined oestrogen and progestogen in oral (tablet) form, and also depends on the type of progestogen used. Some studies suggest a lower risk with non-oral therapy (patches, implants or gels) or tibolone.

Endometrial cancer and HRT

The endometrium is the lining of the uterus. Use of oestrogen-only HRT increases the risk of endometrial cancer, but this risk is not seen with combined continuous oestrogen and progestogen treatment. There is no risk if a woman has had her uterus removed (hysterectomy).

Ovarian cancer and HRT

The increased risk of ovarian cancer is very small and estimated to be one extra case per 10,000 HRT users per year. A recent review linked HRT to two types of tumours: serous and endometrioid cancers.

Cholecystitis and HRT

Cholecystitis is a disease in which gallstones in the gallbladder block ducts, causing infection and inflammation. On average, there is a slightly higher risk that a woman will develop cholecystitis when using oral HRT, but patch treatment is associated with a lower risk. Treatment for cholecystitis includes surgery to remove the gallbladder.

HRT does not cause weight gain

Weight gain at the menopause is related to age and lifestyle factors. An increase in body fat, especially around the abdomen, can occur during menopause because of hormonal changes, although exactly why this happens is not clear. Normal age-related decrease in muscle tissue, and a decrease in exercise levels, can also contribute to weight gain.

Most studies do not show a link between weight gain and HRT use. If a woman is prone to weight gain during her middle years, she will put on weight whether or not she uses HRT. 

Some women may experience symptoms at the start of treatment, including bloating, fluid retention and breast fullness, which may be misinterpreted as weight gain. These symptoms usually disappear once the therapy doses are changed to suit the individual.

Contraception and HRT

HRT is not a form of contraception. The treatment does not contain high enough levels of hormones to suppress ovulation, so pregnancy is still possible in women in the perimenopause (the time of hormonal instability leading up to menopause). 

Periods can be erratic in perimenopause, and egg production will be less frequent, but can still occur until menopause. For women younger than 50, contraception is recommended for at least two years after the final period. For women aged 50 and above, contraception is recommended for at least one year after their final period.

Long-term use of HRT

It is currently believed that, overall, the risks of long-term (more than five years) use of HRT outweigh the benefits. HRT should not be recommended for disease prevention, except for women under 60 years of age with substantially increased risk of bone fractures, or in the setting of premature menopause.

No alternative therapy has yet been clinically proven to reduce a menopausal woman’s risk of osteoporosis, including the use of soy products, phytoestrogens (plant estrogens) and herbal medicines.

Women with liver disease, migraine headaches, epilepsy, diabetes, gall bladder disease, fibroids, endometriosis or hypertension (high blood pressure) need special consideration before being prescribed HRT. In these situations HRT is often given through the skin (transdermally).

Despite the risks of long-term use, in women with severe and persistent menopausal symptoms, HRT may be the only effective therapy. 

Women with premature or early menopause are prescribed HRT long-term because of their increased risks of earlier onset of heart disease, osteoporosis, and some neurological conditions compared to women undergoing menopause around the age of 50 years. Seek specialist advice from a menopause clinic or menopause specialist. Regular check-ups are recommended.

HRT for breast cancer survivors

It is advisable for women with a history of breast cancer to avoid HRT unless other treatments are ineffective, and their quality of life is made intolerable by menopausal symptoms. In these circumstances, HRT should only be prescribed in consultation with the woman’s breast surgeon or oncologist.

Evidence has not conclusively shown that HRT will increase the risk of breast cancer recurring in a woman with a history of the disease. However, oestrogen and progestogens (forms of progesterone) may stimulate some types of cells in the breast and some types of HRT use have been associated with an increase in the risk of breast cancer in women without a history of breast cancer.

Phytoestrogens and history of breast cancer

It is not recommended that women at high risk of breast cancer, or breast cancer survivors, take highly processed soy supplements (which are high in phytoestrogens), but eating moderate amounts of whole soy foods appears to be healthy.

Other treatments for menopausal symptoms

Studies have shown that some prescription medications can reduce hot flushes and sweats. These treatments may be an option if HRT cannot be used for health or other reasons, and should be discussed with a doctor. 

The herbal medicine, black cohosh, may take the edge off hot flushes and sweats, but there is no data to support long-term use. There is also a rare liver condition that may be associated with the use of black cohosh. 

Other complementary and alternative medicines have not been shown to be effective for menopausal symptoms when compared with ‘dummy’ or placebo treatment in research studies. 

Commercially available vaginal moisturisers (such as Replens) may reduce vaginal dryness if used regularly. Consult your doctor about what will work best for you.

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