Alastair MacLennan: HRT fear must end

WHILE menopausal hormone replacement therapy is not risk free, recent strong messages from menopause organisations underline that, according to the current evidence-based literature, for many women, the benefits clearly outweigh the risks.

These messages from the International Menopause Society, American Endocrine Society, North American Menopause Society and Australasian Menopause Society make it clear that HRT benefits symptomatic women under 60 years of age.

Sadly, since the first results of the Women’s Health Initiative (WHI) were announced — and often exaggerated — many women in their 50s have suffered prolonged severe menopausal symptoms because of a disproportionate fear of HRT. This fear has been fuelled by an aggressive alternative medicine industry, the media, some non-clinical groups (perhaps seeking publicity for funding), and the Therapeutic Goods Administration (TGA), which has not revised the dated and inaccurate edicts issued immediately post-WHI.

In the WHI study, there was a reduction in the absolute risk of breast cancer of 8 cancers per 10 000 per annum in hysterectomised women using oestrogen-only therapy over 7 years. In non-hysterectomised women using combined oestrogen–progestogen therapy who had not used HRT prior to the trial there was no statistically significant increase in breast cancer risk. In the latter group, only those women with past HRT exposure showed a significant rise in cancers at 5 years, an increase of 8 per 10 000, or less than 0.1% per annum.

WHI was mostly a study of asymptomatic women who were an average of 13–14 years postmenopause at trial entry. It is now clear that they were not representative of, and were different from, the symptomatic women who take HRT from near the onset of menopause.

WHI did not properly assess the relief of symptoms, and improved sexuality and quality of life, seen in HRT trials near the onset of menopause. Its unvalidated global index did not include the main indications for HRT — symptom control or other important morbidities such as newly diagnosed diabetes, which was reduced in both therapeutic arms of WHI.

The WHI investigators have since revised their 2002 media message that rocked the world, causing up to two-thirds of users to stop their HRT. In 2007 they wrote “the absence of excess absolute risk of coronary heart disease and the suggestion of reduced total mortality in younger (postmenopausal) women offers some reassurance that hormones remain a reasonable option for the short-term treatment of menopausal symptoms”.

Moderate to severe menopausal symptoms occur in about 50% of Western women and may need treatment for 2–20 years, so the meaning of “short-term” differs with each individual.

The benefit-over-risk ratio of commencing HRT varies from being very great in women with a premature menopause to perhaps none in mildly symptomatic women aged over 65 years. Each woman must be assessed individually and the safest and most effective regimen tailored to her needs.

Unfortunately, the downward turn in the HRT market has seen several companies in Australia withdraw their products for commercial reasons. This has disadvantaged some women with special needs.

A variety of unregistered hormones are imported and compounded for women by local pharmacists into expensive buccal troches and gels. These hormones have never had their bioequivalence, pharmacokinetics, dosages, safety or efficacy audited by the TGA, and are touted on the internet as being free of side effects with no scientific basis for these claims.

No alternative menopausal therapy has been shown to be more effective than a placebo and the few registered non-hormonal products for vasomotor symptoms are barely better. Registered HRT remains the only effective therapy for a wide spectrum of menopausal symptoms and when commenced near menopause the benefits outweigh the risks.

Currently, the appropriate indication for HRT is for the treatment of debilitating menopausal symptoms. In younger postmenopausal women with osteoporosis it is effective in reducing fractures as well as menopausal symptoms.

It is still not currently scientifically correct to advocate HRT from near menopause for primary cardio- or neuro-protection. However, it will never be possible to conduct the ideal, placebo-controlled, randomised trial of HRT and therefore we must use the best available data for our clinical decisions.

Misuse of the WHI results has deprived a decade of women of the best years of their lives, and has deprived a decade of men, of the best years of their wives!

Professor Alastair MacLennan is the head of the discipline of obstetrics and gynaecology at the University of Adelaide.

Posted 21 November 2011