The latest on hormone-replacement therapy

The use of hormone-replacement therapy remains a contentious issue. The very latest research confirms that it certainly shouldn’t be used to prevent chronic disease.

It’s a fact of life: when a woman reaches menopause, her hormone levels drop significantly – an important physiological change that could have far-reaching health implications, both in the short and long term.

But not all women who are menopausal need to have that oestrogen and/or progesterone replaced. In fact, research shows that, in many instances, hormone replacement therapy (HRT) could do more harm than good.

Read: The role of hormones in menopause

HRT involves taking low dosages of oestrogen (or, more specifically, the conjugated equine oestrogens) or low dosages of both oestrogen and progestin (conjugated equine oestrogens plus medroxyprogesterone acetate - a synthetic version of progesterone) to relieve short-term symptoms associated with menopause (e.g. hot flushes, night sweats, sleeplessness and vaginal dryness). It's also been prescribed to reduce the risk of long-term disease (e.g. osteoporosis, coronary heart disease).

Over the last few decades, few other medical treatments have been prescribed with quite so much enthusiasm. In fact, at least 40% of postmenopausal women in the United States were using HRT shortly before the Women’s Health Initiative (WHI) trials kicked off in 1993. Before this, no other major, long-term trials were conducted to test the benefits and risks.

Despite five decades of prescribing the treatment, many questions still remain regarding the risks and benefits. This has been highlighted once again by the very latest research, in which many of the women who participated in the original WHI trials were studied during a so-called “extension phase”.

The results of this arm of the research were published in the Journal of the American Medical Association (JAMA) in October 2013.

Right now, mounting evidence suggests that HRT shouldn’t be used for the prevention of chronic disease. However, it seems to remain a relatively good option for the short-term management of menopausal symptoms in younger women.

Read: Why hormone replacement therapy use continues to fall

The Women’s Health Initiative trials
Sponsored by the US National Institutes of Health’s National Heart, Lung and Blood Institute (NHLBI), the two WHI trials followed a group of 27,347 American women, 50-79, over a period of 13 years.

Three groups of women were studied: a group on oestrogen therapy (10,739 women in total), a group on oestrogen plus progestin therapy (16,608 women), and a control group who only received placebo (pills with no active ingredients). Of those who participated in this original trial, 81% agreed to be studied for several years after the initial trials came to an end.

In 2002, the combination (oestrogen plus progestin) part of the trial was unexpectedly halted because it looked like the women on this form of HRT had an increased risk for breast cancer. Two years later, the women on oestrogen-only therapy were also advised to stop taking the therapy – also because analysis showed that it could be increasing their risk for breast cancer.  

Among the different study groups, the researchers primarily looked at rates of developing coronary heart disease (including heart attack), stroke, breast cancer, blood clots in the lungs, colorectal cancer, endometrial cancer, hip fracture and death.

However, they also looked at outcomes in terms of dementia, other cancers, other fractures, diabetes, gallbladder disease, urinary incontinence and classic menopause symptoms (hot flushes, night sweats, sleep disturbances, mood and depression, breast tenderness and joint pain).

Study results
The researchers made several important discoveries:

- The rates of overall illness in terms of all the major diseases studied were 12% higher in women taking oestrogen plus progestin therapy (compared to the control group). After women stopped taking oestrogen plus progestin, there was no effect in terms of illness and death – in other words, the risks and benefits dissipated after intervention.

- In women taking only oestrogen, a significant decrease in breast cancer was seen after intervention (in other words, after they stopped taking the therapy), but most other health outcomes weren’t affected.

- In this group of women (those taking only oestrogen), rates of overall illness and death were similar to those who took the placebo during and after the trial. But, importantly, these results differed by age: for women taking oestrogen alone in their 50s, there was a 16% reduced risk of overall illness and death, while women in their 70s taking oestrogen alone had a 17% increased risk of overall illness and death.

- Both HRT regimens were associated with increased risk of stroke, venous thrombosis, gallbladder disease and urinary incontinence, without clear differences by age. For women on combination therapy, breast cancer was an additional effect. Although the risk of heart attack varied in terms of menopause onset, the overall risks outweighed the benefits across all the different age groups.

- In both regimens, diabetes risk was decreased by 14-19%, while risks of gallbladder disease and urinary incontinence were increased by 50-60%. Benefits for diabetes and risks of urinary incontinence and gallbladder disease lessened after the drugs were stopped.

- Overall, the findings also suggest that HRT has a harmful effect in terms of coronary heart disease among older women, while the results in younger women remain inconclusive.

The most important take-home message, at this stage, is that the findings simply don’t support the use of any form of HRT for chronic disease prevention. However, it still seems to be a “reasonable” option for managing moderate to severe menopausal symptoms.

Like all research studies, this one also had its limitations. For instance, only one dose, formulation and route of administration was assessed in each trial. Multiple outcomes and many different subgroups were examined – something that could have led to false-positive and false-negative results.

For this reason, the researchers are wary of coming to firm conclusions about the above findings. More research is needed.

A complex decision
So, right now, the HRT decision remains a complex one. It’s been well established that the therapy can affect the body in various ways which, in turn, depends on hysterectomy status, age and other individual factors.

At this stage, it’s important to remember that not all menopausal women need HRT. Secondly, it’s very clear that not all women are suitable candidates.

Are you a premenopausal, menopausal or post-menopausal woman? Then it’s of the utmost importance to talk to your doctor about your specific risk factors. For some women, the symptoms of menopause can be severe. If you’re one of them, HRT might be necessary to manage this life stage. Talk to your doctor about how you can reduce your risk for breast cancer at the same time, and discuss the risks and benefits of the different kinds of HRT.

- (Carine Visagie, Health24, January 2014)

- Women’s Health Initiative reaffirms use of short-term hormone replacement therapy for younger women, National Institutes of Health press release, 17 October 2013.
- Manson, J.E. et al. (October 2013). Menopausal Hormone Therapy and Health Outcomes During the Intervention and Extended Poststopping Phases of the Women's Health Initiative Randomized Trials. The Journal of the American Medical Association. Vol 310, No. 13.

Read more:
How hormone replacement tied to lung cancer risk

Why stopping hormone therapy may have its own risks
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