Updated 21 July 2014

HT: effects, benefits and risks

HT is the only treatment that results in a dramatic improvement of all the symptoms of menopause. What are the risks and benefits?


How effective and safe is HT?  

In the 1990’s HT was regarded as the “elixir of youth”and frequently prescribed by gynaecologists to many women, not only for the relief of menopausal symptoms but also as longterm therapy to protect against heart disease, osteoporosis and ageing in general. “Feminine forever” was a catch phrase in the United States at the time.

When the  findings of the five-year Women’s Health Initiative (WHI) study were published in the media in 2002, concern began to mount that HT could increase heart disease, stroke and breast cancer. Many women discontinued their HT in fear of an increased risk for breast cancer and heart disease.

But some of the WHI researchers’ interpretations of the results were flawed, and later, more 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.

Why the confusion? The women who took part in the WHI trial were all older and overweight and many had existing heart disease. The study involved nearly 162 000 women, but their average age was 65 years, and some women only started with HT in their late sixties and even at 70. They also had to have no menopausal symptoms to get into the study. In other words, none of them wore the typical woman who seeks treatment or support today.

When only those women who started HT between 50 and 59 were analysed, the incidence of heart disease actually decreased after the first year of use and there was no increase in the number of strokes. Other studies have shown that the incidence of breast cancer did not increase in the first four years of HT use.

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

There appears to be a window of opportunity early in menopause in which the benefits of hormone therapy far outweigh the drawbacks. 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.

But, 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, nausea, vaginal bleeding or spotting. 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: (+ = benefit, - = risk)


(+) HT relieves symptoms associated with menopause

Symptoms 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. HT involves either only oestrogen hormone therapy (ET) or a combination of oestrogen and progesterone therapy (EPT) in women who have a uterus. Women don’t all experience the same symptoms in the same way. However no woman should have to suffer because oestrogen therapy, whether on its own or with progesterone, really works.

HT definitely relieves hot flushes when used in the correct dosage. It also appears to prevent the development of hot flushes in women starting on HT who have entered the menopause as indicated by the absence of menstruation but who have not experienced hot flushes yet.      Your hot flushes and night sweats (which are actually hot flushes at night) should stop within 14 days after starting HT. You’ll also sleep better and be less moody and your quality of life will improve. HT also appears to prevent the development of hot flushes in women starting on HT who have entered the menopause as indicated by the absence of menstruation, but who have not yet experienced hot flushes.

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. The changes in the tissues of the bladder and urethra and the associated loss of protection against infection-causing germs may cause an increased risk of urinary tract infection, which is another problem often afflicting postmenopausal women. HT can provide the tissues of the urogenital tract with enough oestrogen to improve the 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. It clearly counteracts demineralisation of bone and thus prevents the loss of bone which occurs when women enter menopause. The risk for hip fractures, an indicator of osteoporosis, may decrease from 15 per 10 000 to 10 per 10 000. HT can be regarded as a bone protector. Oestrogen-related drugs such as SERMs (e.g raloxifene)may be  prescribed as chronic medication for the prevention of post-menopausal osteoporosis. Extended use of HT is indeed an option for women who have established reduction in bone mass, regardless of menopause symptoms, for prevention of further bone loss. HT use for osteoporosis should always be inititiated in the early years after menopause.

Not only does this prevent hip and spinal fractures, but the oestrogen also acts on the teeth and jaw. This means that women taking HT are less likely to lose their teeth, once menopausal.

However, HT alone will not counteract osteoporosis. Equally important are other measures such as regular exercise, a sensible, well-balanced diet and avoiding cigarette smoking. In women who are at particular risk of osteoporosis or who have already developed some loss of bone density, a consultation with a gynaecologist and/or endocrine specialist is important, since a combination of HT with other bone-loss preventing drugs may be necessary.

(+) HT reduces the onset of type 2 diabetes.

Large studies indicate that HT may prevent type 2 diabetes. Only 0,61% of women who have received EPT in the WHI study developed type 2 diabetes, comparied to 0,76% in the placebo group. This translates into a 21% reduction in 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. But it seems as if women with type 2 diabetes who use oral ET may require lower doses of antidiabetic medication. Lifestyle changes with the correct diet to control glucose and insulin levels, exercise and anti-diabetic medication are important in the control of type 2 diabetes. But the control of heart disease risk in patients with type 2 diabetes is as important as insulin control. Transdermal HT patches will have less effect on triglyceride levels in patients with metabolic syndrome, have less effect on blood pressure, and will have  less effect on the clotting factors, which are already increased in patients with type 2 diabetes.

(+) 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. This is because oestrogen causes increased growth and cell production of the lining of the womb, which – if excessive – is called endometrial hyperplasia. Atypical cells may or may not be present during this process. If atypical cells are present, there is a risk of cancer developing.

As such, women who took oestrogen alone (called unopposed oestrogen) had a risk of developing endometrial cancer of up to ten times that of the general population. By adding progestin to the HT regimen, this risk is prevented. Progestin is added to HT in different time laps, either for half the cycle or continuously. HT (ET and EPT) is not recommended in women with a history of endometrial cancer.

HT regimens, in which the addition of progestin is continuous, definitely prevent endometrial hyperplasia. However, there are HT regimens in which progestin is given for only 12 days of a cycle of continuous oestrogen therapy, the advantage being that some of the beneficial effects of oestrogens are not counteracted by progestins all the time.

Endometrial hyperplasia, if it develops, does seem to occur more often in women who are taking HT this way. This suggests that continuous combined oestrogen and progestin is the only truly effective form of oestrogen delivery which will prevent endometrial hyperplasia, and so decrease the risk of endometrial cancer.

The fact that there are several types of HT regimens available is based on the different individual responses. If all peri- and postmenopausal women were the same, there possibly would be only one form of HT. The doctor will assess the individual response pattern in order to prescribe the appropriate form of HT.

In women who had a hysterectomy (removal of the womb), the prescription of HT is generally easier. There is no risk of getting endometrial cancer, and oestrogen without progestins can be administered.  

 (+) HT reduces the risk for colorectal  cancer. The use of HT decreases the risk for cancer of the colon. The risk for colorectal cancer may drop from 16 per 10 000 women to 10 per 10 0000 women using HT. 

Benefit for some, risk for others:

(+/-) HT may protect younger women against heart disease, but may increases 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 inititiated 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.

It also seems that HT may increase a women’s risk for heart disease in the first four years of HT use, but may reduce the risk after five years, but this data is not conclusive. It seems as if the longterm use of HT is associated with less accumulation of coronary artery calcium, and thus with less atherosclerotic plaque formation.

Just how much may HT increase the risk for heart disease? According to analysis of the Women’s Health Initiative (WHI) study, about 37 in 10 000 women older than 50 and who are taking HT are likely to develop heart disease, instead of 30 out of 10 000. Therefore, for every 10 000 women on HT, only seven more are likely to develop heart disease. It also appears as this increased risk only applies for the first few years of HT use in older women; thereafter the risk decreases. Remember that this study was done involving older, overweight women who initiated hormone therapy later in life.

Experts conclude that HT should not be prescibed 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 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.

Experts concluded that although HT might have a positive effect on mood and behaviour, 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 increase the risk for stroke for older women, not for younger women

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 ischaemic stroke, whereas other studies showed no effect on stroke risk. The WHI studies showed an increased risk for ischaemic stroke, but no effect on hemorrhagic stroke risk. In the WHI studies about 29 out of 10 000 women older than 50 and taking HT were likely to suffer from a stroke, instead of 21 out of 10 000. This is an increase of eight per 10 000 women. The risk for stroke and pulmonary embolism appeared to increase within the first two years of use in the WHI study. This increase may be followed by a decreased risk. But the decreased risk after two years does not sound enticing enough to counteract the increased risk in the first two years.

Experts conclude that HT is not effective in reducing stroke among women with stablished 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 cannot be recommend for the primary or secondary prevention of stroke.

+/-) HT does not protect against Alzheimers Disease

New findings suggest that natural menopause has little effect on memory or other cognitive brain functions.It appears that HT does not improve memory or any other cognitive abilities. One trial reported on women aged 65 – 79 years showed an increase in dementia incidence in HT use from 12 per 10 000 to 23 per 10 000 per year of EPT. But studies also show that the use of HT in younger women close to menopause might reduce Alzheimer’s Disease, but this data is not adequate.

HT cannot be recommended at any age for the sole or primary indication of preventing cognitive ageing or dementia.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 cannot be recommend for the primary or secondary prevention of stroke.


The risks of HT should be explained in context and relative to existing background risks.
(-) 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: 34 in 10 000 instead of 16 in 10 000 women are likely to suffer DVT. The risk is small and increases with age, but is at its greatest during the first year of treatment. 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 formulations of HT. If any doctor decides to treat an at-risk patient with HT patches, it should however only be under close supervision.

Experts conclude that women with a prior history of deep vein thrombosis or women who possess a specific clotting gene called factor V Leiden, are at increased risk for DVT with HT use.

(-) HT may increase the risk of breast cancer, but not mortality rate

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 risk increases from 45 in 1 000 women 50-70 years without HT, to 47 in 1 000 in women 50-70 years on EPT. This risk is higher when oestrogen and progesterone are used together (as is the case with women who still have a womb). After 10 years of EPT use, 51 out of 1 000 women will develop breast cancer (six extra). After 15 years on EPT, 57 out of 1 000 women will develop breast cancer (12 extra).  

Using a different calculation method, a 50-year-old woman (regardless of combination HT or not) has a 2,8% chance of developing breast cancer by age 60. After five years on HT therapy, a woman’s chance of developing breast cancer by age 60 will be 0,7% higher (3,5%). Compare this risk of 35 in 1 000 women to the following:  If 1 000 women have two drinks daily, or have their first child at age 30 or older, or are obese, but are not taking any HT after age 50, 35 of them are likely to develop breast cancer at age 60.  

Some of the most recent research – looking at many different studies – has come up with a figure of a 2,3% increase in the risk of breast cancer with each year of HT use. This levels off after HT is topped. How this affects women with a family history of breast cancer is still unclear.

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, while the ET arm of the WHI study showed no increase in breast cancer after an average 7,1 years of ET use, with six fewer cases of invasive breast cancer per 10 000 women per year of ET use. Slightly fewer cases of localised breast cancer disease and ductal carcinomas were diagnosed. A large decrease in breast cancer was observed six months after the women stopped ET use. But 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. The use of ET may be associated with an increased risk of recurrence.

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. But a large number of studies show an increased ovarian cancer risk.
Data also suggest that the use of HT for less than five years may not lead to a significant increase in ovarian cancer risk, but that the use of HT for longer periods can be linked to a higher risk. Indications are that ET will lead to higher risks than EPT.

(-) 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.

 Compiled by Mari Hudson, medical editor, Health24. Reviewed and updated by Dr Alan Alperstein, obestetrician and gynaecologists in Cape Town, in February 2011. 



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