HRT in women with cardiovascular disease: Can we start, should we stop?

Most women will spend 30% of their life in menopause. Nearly 75% of them will suffer from hot flushes, sleep disturbances, mood change and even loss of work productivity for more than a decade.1 Hormone replacement therapy (HRT) is the most effective treatment for symptomatic relief, and is highly recommended for 5–10 years in women with symptoms and without contraindications.2,3 Moreover, severe symptomatic vasomotor symptoms have been related to decreased cardiovascular health, and serve as a surrogate to cardiovascular disease.4 Nevertheless, HRT use has become one of the most complex health care decisions facing women in midlife, and most of those women remain untreated despite having symptoms that adversely affect their quality of life. The major change in HRT use occurred after the publication of the initial findings of the Women’s Health Initiative (WHI) in 2002.5 Since then the health benefits and risks of HRT have been under vigorous debate, and actual use has decreased by as much as 80%.6 Before that era, in the late 1990s, HRT was considered beneficial in both primary and secondary prevention of ischemic heart disease (IHD).7 However, WHI and other randomized controlled trials evaluating the effects of HRT on prevention of IHD or atherosclerosis progression have generally shown no overall reduction in cardiovascular events, but, rather, showed increased risk of stroke and deep venous thrombosis.8 Moreover, data regarding women with established IHD also showed no reduction in future cardiovascular events.9 Based on those findings HRT was no longer recommended for the purpose of IHD prevention.10 The timing hypothesis is based on the established data that cardiovascular effects of HRT may vary according to vascular age or time from menopause. This window of opportunity helps understand conflicting study results. In previous observational studies, women were younger (approximately 50 years of age) and closer to menopause when they initiated HRT than were the women included in randomized trials (mean age: in the 60s, typically >10 years past menopause).11 Thus, since the effect of hormone therapy on the progression of atherosclerosis differed according to the health of the underlying vascular tissue, HRT recommendation varies according to cardiovascular risk (Figure 1).12 Algorithm for menopausal symptom management. Reproduced with permission from Kaunitz A and Manson J. Management of Menopausal Symptoms. Obstetrics & Gynecology 2016; 126: 859–876. © 2015 The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health HT: hormone therapy; CVD: cardiovascular disease; ACC/AHA: American College of Cardiology/American Heart Association; SSRI: selective serotonin reuptake inhibitor; SNRI: serotonin and norepinephrine reuptake inhibitor; CEE: conjugated equine estrogen. Many women choose not to start or to discontinue HRT use even if recommended. Discontinuation of HRT can be troublesome owing to rebound vasomotor symptoms, but according to recent publications, might also be related to increased cardiovascular risk. Thus, discussions on HRT use should look both at when to start and how to stop treatment. HRT use is particularly problematic in women diagnosed as having IHD. Guidelines for those women recommend discontinuation of HRT, although risk–benefit of this strategy is lacking.13 Indeed most previous publications looking into the impact of HRT on IHD risk did not show a preventive effect, but also did not show a clear signal of increased risk among users. Recently, a nationwide register of 3322 women aged 40 years or over who survived 30 days after a myocardial infarction and were prescribed HRT showed no certain increased or a decreased risk of re-infarction or death with continuing HRT.14 Their results ruled out a worrisome increase in risk in women with IHD using HRT. It seems that existing data do not support withholding HRT from women with established IHD. Menopause is an extremely important period in women’s lives. Vasomotor symptoms and low quality of life are the hallmark of menopause. Moreover, postmenopausal women with diabetes mellitus or hypertension have an increased cardio-metabolic risk, with a special emphasis on inflammation and elevated risk of cardiovascular disease and mortality. Robust data on HRT direct us to feel comfortable to prescribe it for menopausal symptoms, using the lowest dose necessary for the shortest period possible, to women without contraindications. Today we know for sure that the absolute risk of adverse outcomes is much lower in younger women than in older women, and that the net effect on all-cause mortality in younger women is even favorable. Even in women with established IHD, we should not automatically withdraw HRT. Over ‘protection’ of menopausal women with IHD might be even harmful! In particular, abrupt cessation of HRT use in women younger than 60 years might be related to increased cardiovascular risk, combined with recurrence of severe symptoms and low quality of life. We should also keep in mind that for women who cannot be treated with oral HRT, there are other options. We can use new hormone formulations – including those with lower doses and transdermal route of delivery. We can use non-hormonal treatments such as complementary medicine and selective serotonin reuptake inhibitors. There is always an option! Nowadays, we still do not provide adequate education and information to midlife women struggling with menopausal symptoms. All clinicians, including cardiologists and cardiac nurses need to be aware of their vital role in patient education and counselling.15 We must change the atmosphere of our reluctance to deal with this important medical, psychological and social issue. Adequate training of all health care givers of HRT use, and a proper discussion with every woman, will help facilitate better care and quality of life.16 All women, including those with established IHD, deserve to be informed about HRT. If there is an indication for its use and no contraindication – then we should give it!