31 July 2017

MHT – are there any stopping rules?

Clinical Endocrinology Women

Anyone who has prescribed menopausal hormone therapy (MHT) for women with menopausal symptoms will be familiar with the advice, quoted on all product information, that one should use the lowest dose for the shortest amount of time.

This is hardly a statement which facilitates discussion regarding the possible benefits of MHT.  It is, however, a statement which leads many doctors to encourage their patients to cease MHT after five years.

What are the beliefs upon which this statement is based?

First, there is the belief that menopausal symptoms are a short-term, benign nuisance which resolve within a few years after the last menstrual period. In fact, the median duration of vasomotor symptoms is eight years after the LMP, and 20% of women have troublesome symptoms well into their 60s and 70s (1). Vasomotor symptoms of the menopause are associated with lack of sleep and consequent fatigue and reduced functioning in daily and in working life.

Secondly, the low-dose/short term approach is predicated by the concern over breast-cancer risk. This overlooks the fact that, for the woman over 50, cardiovascular disease is, by far, her most dangerous enemy (2). Conversely there is ample evidence that oestrogen is a protective factor for cardiovascular health and that oestrogen deficiency, as with early menopause, leads to greater cardiovascular morbidity (3).

What are the cardiovascular safety data surrounding continuation of MHT?

In several studies, continued use of MHT has been shown to reduce the incidence of cardiovascular events compared with placebo. In the WHI study cardiovascular events reduced over time of exposure to MHT compared with placebo (4).  A large study in Finland showed that MHT use reduced cardiovascular death and the reduction was positively related to time of MHT use (5).

More recently, again in Finland, Mikkola has examined the cardiac or stroke deaths occurring in women who stop MHT.  He has compared the event rate in those who stop with that in women who continued MHT.  He has found a significant increase in deaths in those who stop, whether MHT was taken for less than or more than 5 years (6).

The putative mechanisms are many: withdrawal of non-genomic vasodilatory effects of oestrogen, reduced oestrogen-induced nitric oxide gene expression, increased sympathetic and decreased parasympathetic activity associated with the return of hot flushes, or return of palpitations and arrythmias associated with oestrogen withdrawal.

In short, it does not appear that continuation of MHT for menopausal symptoms is deleterious to cardiovascular health – quite the reverse.

Recent guidelines published by the International Menopause Society recommend that there be no mandatory limit to MHT prescribing. (7)  It should be used in the dose required to address the treatment goals and for as long as there is a need.

Of course, one may adjust the mode of delivery and the type of MHT according to age and circumstance. There is one agreed stopping rule and that is oestrogen-dependent cancer, although even that may be a relative contraindication depending on circumstance.

The advice to use MHT in the lowest dose and for the shortest amount of time is not supported by the data.

References:

  1. Gartoulla P, Worsley R, Bell RJ, Davis SR. Moderate to severe vasomotor and sexual symptoms remain problematic for women aged 60 to 65 years. Menopause. 2015;22(7):694-701.
  2. Causes of Death, Australia, 2015 [database on the Internet]2016.
  3. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340(23):1801-11.
  4. Rossouw JE, Prentice RL, Manson JE, Wu L, Barad D, Barnabei VM, et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA. 2007;297(13):1465-77.
  5. Mikkola TS, Tuomikoski P, Lyytinen H, Korhonen P, Hoti F, Vattulainen P, et al. Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality. Menopause. 2015;22(9):976-83.
  6. Mikkola TS, Tuomikoski P, Lyytinen H, Korhonen P, Hoti F, Vattulainen P, et al. Increased cardiovascular mortality risk in women discontinuing postmenopausal hormone therapy. J Clin Endocrinol Metab. 2015;100(12):4588-94.
  7. Baber RJ, Panay N, Fenton A, Group IMSW. 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy. Climacteric. 2016;19(2):109-50.

 

Professor Stuckey, BA MBBS FRACP, is an endocrinologist with a clinical and research interest in reproductive endocrinology

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