Menopausal hormone therapy – good or bad for CVD?

29th August 2026, A/Prof Chee L Khoo

Menopause

The European Society of Endocrinology clinical practice guideline for evaluation and management of menopause and the perimenopause recommend that a holistic approach is taken for women during perimenopause and menopause, not having a sole focus on hormone replacement therapy (HRT)/ menopausal hormone therapy (MHT) (1). It recognised that these women can be appropriately managed in primary care according to recognised guidelinesIt also recommend initiating MHT in women within 10 years of natural menopause onset or under 60 years for bothersome menopausal symptoms such as vasomotor or other climacteric symptoms. In relation to CVD though, it specifically mentioned that MHT should not be used primarily for primary or secondary prevention of cardiovascular disease. So, is MHT good or bad for CV risk in menopausal or perimenopausal women?

A significant proportion of postmenopausal women experience debilitating vasomotor symptoms (VMS). MHT remains the most effective treatment for VMS and the genitourinary syndrome of menopause. However, there are risks which differ depending on type, dose, duration of use, route of administration, timing of initiation, and whether a progestogen is used. The risk is also affected by the age when the woman became menopausal, when MHT was commenced and the existing CV risk of the woman.

There has been signals of potential CV harm for some years now. Huang et al reported from the Heart and Estrogen/Progestin Replacement Study (2009) that older postmenopausal women with pre-existing coronary heart disease (CHD), estrogen plus progestogen therapy (EPT) may increase risk of CHD events substantially in the first year of treatment among women with clinically significant hot flushes but not among those without hot flushes (2). The mean age of participants was 66.7 ± 6.8 years, and 89% (n = 2,448) were white. Sixteen percent (n = 434) of participants reported clinically significant hot flushes at baseline. Among women with baseline flushing, EPT increased risk of CHD events nine-fold in the first year compared with placebo (hazard ratio = 9.01; 95% CI, 1.15-70.35).

Based on observational data and reanalysis of older studies by age or time since menopause, including the WHI, the 2022 Hormone Therapy Position Statement of The North American Menopause Society suggested that for healthy women who are within 10 years of the menopause transition and who have bothersome menopause symptoms, the benefits of hormone therapy (ET or EPT) outweigh its risks, with fewer CVD events in younger versus older women (3). Women who initiate hormone therapy aged older than 60 years or more than 10 or 20 years from menopause onset are at higher absolute risks of CHD, VTE, and stroke than women initiating hormone therapy in early menopause.  

The 2022 position was supported by a Secondary Analysis of the Women’s Health Initiative Randomized Clinical Trials (2025) found that MHT did not significantly affect ASCVD risk in younger women (4). In contrast, MHT increased cardiovascular disease risk in women older than 70 years with vasomotor symptoms.

It is quite clear that we need to be careful when we have to treat VMS in older post menopausal women. We don’t have that many women in that category but all is not necessarily rosy for younger patients either. A most recent study (July 2026) clarified the other factors which influence our decision to initiate MHT or not. Rossouw J, et al conducted a secondary analysis of two double-blind placebo-controlled randomized controlled trials of conjugated equine estrogens ([CEE] 0.625 mg/d) or CEE with medroxyprogesterone acetate ([MPA] 2.5 mg/d) compared with placebo in postmenopausal women aged 50–79 years (5). The primary outcome was coronary heart disease ([CHD], nonfatal myocardial infarction or CHD death). Cardiometabolic status was evaluated by lipid profile, blood pressure, blood glucose, and presence of metabolic syndrome (MetS).

They threw an additional factor this time, dyslipidaemia. Randomisation to oral MHT did not increase CHD risk in participants with a history of treated hyperlipidaemia or in untreated participants with favourable lipid profiles, but risk increased in those with unfavourable lipid profiles. The CHD risk in untreated participants with normal low-density lipoprotein (LDL) cholesterol levels (less than 130 mg/dL) was similar to that of placebo-treated participants (hazard ratio [HR] 0.59; 95% CI, 0.31–1.10); however, for elevated LDL 190 mg/dL or higher, the risks were more than doubled (HR 2.77; 95% CI, 1.42–5.40; P-trend=.002). Prior treatment of hyperlipidemia demonstrated no increased risk of CHD in patients treated with CEE+MPA or CEE compared with those receiving placebo.

There is no question that VMS can be quite debilitating  to the women in perimenopause or in menopause. Many guidelines have recommended that MHT should be offered to these women but there are potential risks we need to be mindful of. The new study just released suggest we need to look at dyslipidaemia critically when we initiate MHT even in younger women. While women with known CHD shouldn’t be on MHT, there are many asymptomatic and sub-obstructive CAD in women which run into the same problem as those with known CAD.

References:

  1. Lumsden MA, Dekkers OM, Faubion SS, et al. European society of endocrinology clinical practice guideline for evaluation and management of menopause and the perimenopause. Eur J Endocrinol. 2025 Sep 30;193(4):G49-G81.
  2. Huang AJ, Sawaya GF, Vittinghoff E, Lin F, Grady D. Hot flushes, coronary heart disease, and hormone therapy in postmenopausal women. Menopause. 2009 Jul-Aug;16(4):639-43.
  3. “The 2022 Hormone Therapy Position Statement of The North American Menopause Society” Advisory Panel. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022 Jul 1;29(7):767-794.
  4. Rossouw JE, Aragaki AK, Manson JE, et al. Menopausal Hormone Therapy and Cardiovascular Diseases in Women With Vasomotor Symptoms: A Secondary Analysis of the Women’s Health Initiative Randomized Clinical Trials. JAMA Intern Med. 2025 Nov 1;185(11):1330-1339.
  5. Rossouw JE, Aragaki AK, Manson JE, et al. Influence of Cardiometabolic Status on Cardiovascular Effects of Oral Menopausal Hormone Therapy. Obstet Gynecol. 2026 Jul 24:10.1097/AOG.0000000000006381.