18 February 2016

How safe is hormone therapy?


Rational analysis of the WHI trial results and subsequent studies proved that HT, when used correctly and for the right patient, is good for you. Experts now believe that HT is perfectly safe, provided it’s used correctly.

Effective hormone therapy is dependent on the patient’s individual profile. Age is the most important determinant when it comes to assessing benefits and risks and it is recommended that HT is used as soon as possible after menopause starts and not, for instance, only years later. In general, when using approved hormone-replacement therapies, the American Food and Drug Administration and healthcare professionals recommend using the lowest dose possible for the shortest period needed.

The benefits and risks of HT 

Users of HT experience improvement in their quality of life and reap the benefits of both decreased menopause symptoms, increasing bone density, and – in some women – reduced risk for heart disease. If you’re a suitable candidate for HT, the sooner you start, the more effective it will be. It is always best to start HT treatment, when indicated, as soon as possible (never later than five years after menopause) and at the lowest dosage possible.

Possible side-effects of HT

As with all drugs, there are side-effects and risks associated with HT. Possible side-effects are far from life-threatening and may include bloating, headaches, breast tenderness, nausea, the return of vaginal bleeding or spotting. It may cause hypertension in some patients. All will be reversed as soon as HT is stopped. 

The risks include the possibilities of cancer of the endometrium (lining of the womb), breast cancer, breast soreness, vaginal bleeding, high blood pressure and blood clots in the veins (venous thrombosis). The side effects and risks are now much lower than  a decade or two ago because much lower dosages of HT (about 25%) are now used than 10 and 20 years ago. Since the oestrogen is not replaced to its previous pre-menopause levels, the term hormone replacement therapy is no longer used, but rather hormone therapy (HT).

Note that the higher risks end with the treatment – but so does the protection against osteoporosis and diseases such as colorectal cancer.

The effect of HT on the body can be summarised as follows:

HT relieves symptoms associated with menopause such as hot flushes, night sweats and vaginal dryness. In fact, HT is the only treatment that results in a dramatic improvement of all the symptoms of menopause. You’ll also sleep better and be less moody and your quality of life will improve.

HT can also provide the tissues of the urogenital tract with enough oestrogen to improve their function and to prevent vaginal dryness and recurrent bladder infections.

HT reduces the risk of developing osteoporosis. HT also reduces the possibilities of osteoporosis if you start the therapy as soon as possible after menopause. Oestrogen-related drugs such as SERMs (e.g. raloxifene) may be prescribed as chronic medication for the prevention of post-menopausal osteoporosis.

HT reduces the onset of type 2 diabetes. Large studies indicate that HT may prevent type 2 diabetes. The reduction may be due to less weight gain around the belly, reduced insulin resistance or other unknown factors. HT is also associated with an improvement in insulin resistance in post-menopausal women. However, there is not enough evidence to recommend HT as the sole or primary indication for the prevention of type 2 diabetes in menopausal women.

EPT decreases the risk of cancer of the endometrium. The use of HT decreases the risk for cancer of the endometrium. In the past, HT was administered only as oestrogen with no addition of progestin, and a woman who still had her womb intact had the risk of developing cancer of the endometrium. By adding progestin to the HT regimen, this risk is prevented. HT (ET and EPT) is not recommended in women with 

a history of endometrial cancer. Continuous combined oestrogen and progestin seems to be the only truly effective form of oestrogen delivery which will decrease the risk of endometrial cancer. HT reduces the risk for colorectal cancer. The use of HT decreases the risk for cancer of the colon.

HT may improve or worsen mood and depression. Several studies suggest that perimenopausal and early postmenopausal women are at an increased risk of developing depression. Some studies suggest that HT may improve mood, while others show no effect on mood. 

Progestogens in EPT may worsen mood in some women, particularly those with a history of premenstrual syndrome, premenstrual depressive disorder or clinical depression. However, HT is not an antidepressant and should not be prescribed to treat depression. It is of interest to note that SSRI anti-depressants may indeed even alleviate hot flushes in some women.

HT may protect younger women against heart disease, but may also increase the risk for older women. Careful analysis of studies indicated that HT may reduce the risk for heart disease if HT is initiated within two to three years after the onset of the menopause in woman age 50 – 59. However, indications are that HT, when initiated more than ten years beyond menopause in women older than 63 years, may increase a woman’s risk for coronary heart disease. These are indications, not absolutes.

Experts conclude that HT should not be prescribed to primarily reduce the risk of heart disease. The correct treatment options for patients with an increased risk for heart disease include antihypertensives, cholesterol-lowering drugs and other medication, aimed to decrease the specific risk factors.

HT may increase the risk for stroke. Results of studies of the risk of stroke with HT have been inconsistent. Some studies, including the very large Nurses’ Health Study (NHS) and the WHI study, indicated an increased risk of ischemic stroke, whereas other studies showed no effect on stroke risk.

Experts conclude that HT is not effective in reducing stroke among women with established cardiovascular disease or for prevention of a first stroke, and it may increase the rate of first strokes, particularly in women starting with HT after their 60th birthday.

HT increases the risk of blood clots and deep vein thrombosis (DVT). The risk of developing blood clots is higher among patients older than 60 but there is no evidence that this increases the risk of death as a result of the clots. In fact, the risk is less than half of that during normal pregnancy. Women who have already had venous thrombosis have an increased risk of suffering further clot formation if they take oestrogen orally. 

However, according to observation this seems to be diminished if they use transdermal patches of HT. Experts conclude that women with a prior history of deep vein thrombosis or women who possess a specific clotting gene 'like Leiden V are at increased risk for DVT with HT use.

HT may increase the risk of breast cancer. There is a slightly increased risk for breast cancer, especially after five or more years of HT (particularly EPT) use. Despite the increase in breast cancer incidence, the mortality is unchanged. It seems that breast cancer is detected earlier in women on HT because of increased awareness and annual mammographies.

The current consensus is that there is some increased risk of breast cancer associated with HT, particularly when HT had been started soon after menopause. The increased risk is more related to EPT use. However, when ET was extended beyond 10 to 15 years, breast cancer seemed to increase.

The use of ET in breast cancer survivors is still controversial. There is still no proof that ET use in breast cancer survivors is safe.
Remember, the risk varies widely among women, so individual risk factors need to be evaluated before starting HT. It is also worth remembering that deaths from coronary artery disease among women outnumber deaths from breast cancer, so the relative risk of both conditions needs to be assessed as well.

HT may increase ovarian cancer risk after longer use. Data on the role of both ET and EPT and the risk of ovarian cancer is conflicting. Many studies show either no association or a slight increased risk with HT use.

HT use in older smokers may promote lung cancer. Overall WHI data suggest that EPT, when initiated in older women with a history of smoking, may promote the growth of existing cancers. All smoking women in any stage of their life should be encouraged to stop smoking.

HT does not protect against Alzheimer’s disease. New findings suggest that natural menopause has little effect on memory or other cognitive brain functions. 

Read more: 

How menopause harms the body  

Treating menopause 

Diagnosing menopause 

Reviewed and updated by Dr Dr Carol Thomas MBChB (UCT) FCOG (SA) MMed (O&G) (UCT), Specialist Gynaecologist in private practice, Cape Town, Secretary South African Menopause Society and Director of the WomanSpace. March 2015.

(Previously reviewed by Dr Mike Davey, President of the South African Menopause Society, and Prof B. Schaetzing MD, FCOG (SA), FRCOG, PhD. Part-time Consultant, Dept of Obstetrics & Gynaecology, Faculty of Health Sciences, University of Stellenbosch)