A life-changing experience: menopause and hormone replacement

As a physician, I am often reminded that life indeed is a question of timing. When to intervene and when not to intervene is a common dilemma when dealing with the human body. On a scientific level, the question can be posed constantly. When is the right time to prevent a disease.

As human beings continue to evolve and as medicine continues to advance I believe this question will become ever more prevalent in our health care paradigm.

When faced with the treatment disease we much continuously ask when is the “point of no return” and when is the “turning point”.

Such is indeed the case with many of life’s natural aging processes. Remember not all bodily malfunctions are diseases. Sometimes the body just ages as a natural function of the process itself.

And by this, I mean menopause.

The issue comes down, again to one of timing. A volume of population data shows that a woman’s risk of cardiovascular disease begins to rise after she goes through menopause. This epidemiological data prompted a variety of theories on the cardio protective effects of estrogen and progesterone.

Hormone replacement therapy

Hormone replacement therapy made its therapeutic debut in the 1960’s for the treatment of symptoms of menopause. Women with vasomotor symptoms (hot flashes, sleep disturbance, palpitations) and mood disorders were offered an option.

For much of the 1990’s there was an assumption that indeed hormone replacement therapy (HRT) decreased a woman’s risk of cardiovascular disease.

And then came the Women’s Health Initiative (WHI). The WHI was a set of clinical trials first launched in 1991 that was designed to look at effects of hormone replacement therapy on cardiovascular disease and osteoporosis in postmenopausal women. The study was randomized, meaning half the patients in the study randomly were chosen for treatment and half received placebo.

One group within the WHI included women ages 50-79 who had not had a hysterectomy. They were randomized to in the estrogen plus progestin group or placebo.  In total 16,609 women were enrolled from 1991 until the study was stopped and published in 2002.

Remember that before the study launched, HRT was thought to prevent heart disease. The results of the Women’s Health Initiative indeed disproved this.

Women on estrogen plus progestin therapy had a 22 per cent increase in total cardiovascular disease, a 29 per cent increase in heart attack and a 41 per cent increase in strokes relative to women taking no therapy. To put this in context there were 2 more cardiac events (heart attacks and strokes) for every 10,000 women taking HRT per year.

The study also showed that HRT conferred an increased risk of breast cancer by more than 25 per cent, but a benefit for hip fracture prevention and colon cancer reduction. I won’t discuss the details of this here but will focus on the cardiovascular risk angle.

When the WHI launched its results in 2002 women were quite frankly scared. Many who had been on HRT for years were now being taken off of it. The perception was that they had been on a harmful agent for years and any minute now, the effects would be seen. There was a sense in the medical community that this was now a seriously dangerous therapy.

But again, like many things in medicine- hormone replacement therapy can be seen as a question of timing.

Firstly, the WHI study has been widely criticized for the patients it enrolled and the high dose of HRT used.

In the WHI 66 per cent of participants began taking HRT after the age of 60,  21 per cent began taking it after the age of 70. These were women who had never been on HRT and were now started on it postmenopausal as part of the study protocol. Many of whom had been through menopause more than 10 years before. The study itself did not test the benefits and risks of HRT for menopausal symptoms. The dose of HRT in the WHI was much higher than that used for symptom relief.

This was originally a therapy that was designed to relieve symptoms and to be taken for a short period of time in women around aged 50 who were indeed transitioning into menopause. Who would even think to put a woman in her 60’s or even 70’s on hormone replacement therapy? The only reason this was done was because there was this perception that perhaps HRT would indeed prevent disease.

Smaller trials

Since the Women’s Health initiative, two smaller trials have been published to offer reassurance to women who indeed want to take HRT at a younger age and for symptom relief.

One such study is the Kronos Early Estrogen Prevention Study (KEEPS). In this trial women were randomized to HRT or placebo within three years of their last menstrual period. There was no difference in heart attack or cardiac death in women on hormone therapy than in women on placebo.

Make no mistake- I’m NOT suggesting a return to hormone therapy for all. I suspect this controversy surrounding HRT in women is not over. But I do think it is now a question of timing. In certain low risk women there is good evidence for the safety of instituting hormone replacement therapy for women who are EARLY in menopause and specifically for symptom relief.

Who benefits?

The key to making sense of the HRT debate is to understand WHO benefits most from this therapy and why.

Firstly- always talk to your doctor before starting or stopping any therapy.

Secondly- if you are a woman with a low risk of cardiovascular disease and you are having significant symptoms of menopause and are looking for a treatment option then hormone replacement therapy may be right for you.

Data from women over 65 on HRT should not be applied to the 51-year-old woman who needs a short-term solution for treatment.

Understand that you ARE taking it for symptom relief only. Understand that it is NOT to prevent you from having a heart attack. There are far more significant things a woman CAN do to prevent heart disease (just wait for my article on exercise). Finally understand that this therapy in the appropriate situation is indeed safe and effective for symptoms of menopause.

Current Canadian guidelines do indeed recommend LOW DOSE HRT as an OPTION for low risk women for menopausal symptoms who are within 3 years of menopause.

Timing may not always be everything, but often in medicine timing and a little bit of perspective can indeed  make all the difference.

For more information:

References:

1. Grodstein F, Stampfer M. The epidemiology of coronary heart disease and estrogen replacement in postmenopausal women. Prog Cardiovasc Dis1995;38:199-210.

2. Grodstein F, Stampfer MJ. Estrogen for women at varying risk of coronary disease. Maturitas1998;30:19-26.

3. Grodstein F, Stampfer MJ, Manson JE, Colditz GA, Willett WC, Rosner B, et al. Postmenopausal estrogen and progestin use and the risk of cardiovascular disease. N Engl J Med1996;335:453-61.

4. Dubey RK, Imthurn B, Barton M, Jackson EK. Vascular consequences of menopause and hormone therapy: importance of timing of treatment and type of estrogen. Cardiovasc Res2005;66:295-306.

5. Hodis HN, Mack WJ. A “window of opportunity:” the reduction of coronary heart disease and total mortality with menopausal therapies is age- and time-dependent. Brain Res2011;1379:244-52.

6. Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative randomized controlled trial. JAMA2002;288:321-33.

7. Jensen LB, Vestergaard P, Hermann AP, Gram J, Eiken P, Abrahamsen B, et al. Hormone replacement therapy dissociates fat mass and bone mass, and tends to reduce weight gain in early postmenopausal women: a randomized controlled 5-year clinical trial of the Danish Osteoporosis Prevention Study. J Bone Miner Res2003;18:333-42.