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Night Sweats/Sleep Problems, Hot Flushes and Heart Disease – April 2026 Newsletter

Jerilynn C. Prior BA, MD, FRCPC, Professor Emerita, Endocrinology/Medicine University of British Columbia

Healthy aging matters to me as someone approaching age 83, as a retired physician who has evaluated and cared for many people of adult and older ages, and as a scientist puzzling over controversies related to benefits or not of taking menopausal hormone therapy (MHT).

It is foolish to believe that healthy aging will be accomplished by taking some potion or peptide, some protein or probiotic. Nor is it helped by some wrinkle-relaxing facial cream. It is helped, by maintaining, or better-late- than-never, starting a healthy fresh food nutrient-dense diet and regular at least walking exercise.

As I was writing a review of progesterone and healthy aging1, I came to an important, novel understanding: we can likely prevent heart disease by effective treatment of night sweats/sleep problems and hot flushes.

When perimenopause begins (and it can start during regular cycles in women+ as young as 35)2, it can disturb almost everything about the lives of people with ovaries who are still menstruating (for short, perimenopausal women+ of all chosen genders). Thankfully probably 75% of women+ who have appropriate support and who understand what and why things are changing, sail through perimenopause with minor disturbances.

But that means that approximately a quarter of us, like me, in perimenopause will be intensely bothered by the wildly swinging and higher estrogen levels causing night sweats (and the sleep disturbances inevitably associated with3) and hot flushes. Down-swinging estrogen levels not only trigger night sweats but also a huge release of stress hormones, neurotransmitters and everything we know how to measure4! And VMS that start in perimenopause often extend into menopause for a few years 5.

Also, we now know that night sweats are associated with physiological and heart-risking changes such as higher blood pressure6. Hot flushes may make us embarrassed in public, or we may believe we are able or not able to manage these night sweats and hot flushes (together called vasomotor symptoms, VMS)7. But that is not all.

What do we know about VMS and heart disease?

We know from the large USA Women’s Health Initiative (WHI) randomized controlled trials (RCT)* of hormones that menopausal hormone therapy does not prevent heart disease or an increase in its risk factors like blood clots. These were two placebo-controlled RCTs including separate ones for women in general treated with estrogen and a progestin (E+p) and for women who have had a hysterectomy treated solely with estrogen (E-alone). These trials asked an important question:

Does estrogen therapy prevent heart disease in women who are not seeking treatment for the changes of menopause?

*If you are familiar with the WHI trials you can skip the next couple of paragraphs.

The WHI E+p8 and E-alone9results both showed that there was no prevention of heart disease. They also showed that these women, treated for prevention of menopause itself (remembering that most thought then that menopause was a disease of estrogen deficiency) were not helped by estrogen-dominant therapy although mortality (risk of death) was unchanged. In the E+p RCT, for example, coronary heart disease was increased by 29% (hazard ratio [HR] 1.29) in those on hormones versus placebo8. In the E-only RCT the results showed no difference in heart attacks (hazard ratio 0.91 [0.75-1.12]) between those on estrogen versus placebo9. Also, both studies showed increased risks for blood clots8 9 and the E-only also showed more strokes.

Are the WHI trials the only evidence that estrogen for prevention doesn’t decrease heart disease?

No. If you are one who considers the WHI trials to be deeply flawed and not accurate, I’d like to share results of MHT and heart attack prevention in another study. Clearly, with the 20-20 vision of hindsight, the WHI hormone trials used the wrong kind of hormones and estrogen was delivered in a less physiological way. The third and fourth RCTs showing lack of MHT heart disease prevention are the Kronos Early Estrogen Prevention Study or KEEPS trials which included about 7,000 asymptomatic, early-in-menopause women. KEEPS enrolled too few women and followed them for too few years to have heart attacks as its primary outcome. So, they assessed carotid intimal media thickness (CIMT), a measurement of a layer of cells in the carotid artery carrying blood to the brain; if it becomes thicker, it is a robust heart disease predictor.

KEEPS randomized asymptomatic women who were recently menopausal and aged 42-58 years old who received the same conjugated equine oral estrogen as in the WHI trials but in a slightly lower dose (.45 versus .625 mg/day) with cyclic oral micronized progesterone (200 mg at bedtime for 12 days a month). The other parallel RCT gave natural estrogen as the estradiol patch (transdermal) 50 micrograms daily also with cyclic progesterone10. Neither of these randomized trials showed a difference between CIMT on either of the two kinds of hormones versus placebo. In addition, CIMT increased annually and by the same amount on placebo as on MHT10. It showed no heart risk prevention in these asymptomatic women. 

So, these two more randomized, placebo-controlled prevention studies also showed that estrogen-based MHT does not prevent heart disease.

Therefore, we know that MHT does not prevent heart disease in women without night sweats and hot flushes. But, by contrast, multiple large observational studies show MHT is significantly associated with lower risks for heart diseases11 12.

As I was writing the big review of progesterone and healthy aging1, I again pondered the difference between the prevention trials and observational MHT treatment studies. I suddenly had an important question: Does treating VMS with MHT in menopause or with progesterone in perimenopause prevent heart disease?

Before we go over the evidence to answer that question, let’s review one of the early MHT heart disease prevention studies.
 
I remember back in 1991 reading the New England Journal of Medicine Nurses’ Health Study data results that found those taking MHT had their risk for heart disease cut in half11. I looked critically at the characteristics of women who took MHT and those who didn’t.  More MHT-taking women did vigorous physical activity, fewer smoked, fewer were obese, and fewer had diabetes11. We know that all of those things, by themselves, prevent heart attacks. However, the women who took MHT were also more likely to have a close relative with a heart attack and more of them had high blood pressure which should have increased their heart attack risk. The researchers of this observational, non-randomized study statistically adjusted for the differences in those taking MHT and those not-taking MHT and still found MHT was related to heart disease prevention.

I looked more closely and saw that almost 50% of those in the taking-MHT group had undergone a surgical menopause (both ovaries removed) and some of these women had become menopausal as early as age 30 11! We know that both a surgical menopause and an early age at menopause would have markedly increased these women’s risks for heart attack. I also knew that the oral conjugated equine estrogen (PremarinÒ), the only estrogen treatment then available, caused blood clots and high blood pressure that are both linked to heart attacks.
 
I audaciously and rather naively wrote a letter to the NEJM editor saying that women who had healthier lives were the ones who took estrogen-dominant MHT13. I stubbornly said I would not believe that estrogen (in MHT) prevented heart attacks until randomized controlled trial (RCT) results showed this. That was about 10 years before we learned the first of the results of the randomized WHI prevention trials of estrogen alone (for women with a hysterectomy) and estrogen with progestin for women without.

Reading it again now it strikes me as a huge deficiency that this article, quoted by over 1300 other authors, provided no information about why their doctors prescribed MHT.

What about Night Sweats, Hot Flushes (VMS) and Heart Disease?

Dr. Rebecca Thurston, a major investigator in the Study of Women Across the Nation (SWAN) examining perimenopausal women in multiple USA centres of differing ethnicities, looked at those who had the worst baseline and most persistent VMS. She found something that was startling. Those with problematic baseline VMS (on more than six days in two weeks) had more cardiovascular disease (heart attacks, strokes, heart failure, coronary artery surgeries) during follow-up14. She found an even stronger relationship when she examined those whose VMS was persistent. Those with VMS reported on more than a third of all follow-up visits were 77% more likely to develop heart disease, or strokes (HR [95% CI], 1.77 [1.33–2.35], P <.0001)14.  

Why were these symptomatic women not treated? Their night sweats (that start before daytime hot flushes in perimenopause15) were continuing, especially just before their period 16 to wake them at night sweating. For whatever reason, their night sweats and sleep problems were not effectively treated.
 
Why not?

Here it gets even more controversial. Because there is no evidence that estrogen-dominant MHT is effective in perimenopause. We know that estrogen improves VMS in menopause, based on multiple RCTs17; estrogen with progestin is even more effective17. But an RCT in 132 perimenopausal women showed that the Pill (combined hormonal contraceptives which are estrogen-dominant) did not improve perimenopausal VMS more than placebo18. No large RCT of MHT as effective for perimenopausal VMS has ever been published.
 
However, the good news is that oral micronized progesterone significantly decreased night sweats and markedly improved sleep in our Canada-wide RCT in 189 perimenopausal women15.

Here I am going beyond what RCT data show. I think the reason MHT is helpful for heart disease in general population menopause studies is that problematic VMS were effectively treated for the majority. The high stress hormone state that triggers and is essential to VMS4 is calmed and decreased by MHT in menopause. VMS decrease and so do risks for heart disease.

So, what about perimenopause? Since we don’t effectively treat perimenopausal VMS with MHT, we see night sweats/sleep problems and hot flushes persisting and heart disease developing. I believe that perimenopausal heart disease would decrease if women having night sweats/sleep problems were treated with progesterone which we know is effective for night sweats and sleep disturbances15.
 
The big missing variable in all of the observational trials is recording of why women were prescribed and took MHT.

The bottom line — VMS in perimenopause and menopause and heart disease:

  • If you are perimenopausal and have night sweats disturbing sleep more than twice a week (what we found was common in those with problematic VMS in perimenopause)15, you should ask your healthcare provider for a prescription for 300 mg of oral micronized progesterone at bedtime daily15. Stop once a year to see if the night sweats have gone19, if not, start again and continue as needed and into menopause, checking once per year as described above.
     
  • If you are menopausal and have hot flushes and night sweats that are problematic, ask your healthcare provider for oral micronized progesterone20 which you can continue as needed; alternatively you could ask for transdermal estradiol at the lowest effective dose, with 300 mg of progesterone at bedtime. I think estradiol should not be continued longer than five years because of its known risks in older women, but progesterone can be continued as long as it is needed.
     
  • If you don’t have problematic symptoms, remember that perimenopause and menopause are a normal part of a woman’s life cycle and that the hormonal changes do not, by themselves, need treatment.
Reference List
  1. Prior JC, Vitzthum VJ. Progesterone for reproductive vitality and women’s healthy ageing. Exploration of Endocrine and Metabolic Diseases 2026;3 doi: 10.37349/eemd.2026.101460
  2. Coslov N, Richardson MK, Woods NF. “Not feeling like myself” in perimenopause – what does it mean? Observations from the Women Living Better survey. Menopause 2024;31(5):390-98. doi: 10.1097/GME.0000000000002339 [published Online First: 20240323]
  3. Mold JW, Mathew MK, Belgore S, et al. Prevalence of night sweats in primary care patients: an OKPRN and TAFP-Net collaborative study. J FamPract 2002;51(5):452-56.
  4. Freedman RR. Menopausal hot flashes: mechanisms, endocrinology, treatment. J Steroid BiochemMol Biol 2014;142:115-20.
  5. Freeman EW, Sammel MD, Sanders RJ. Risk of long-term hot flashes after natural menopause: evidence from the Penn Ovarian Aging Study cohort. Menopause 2014;21(9):924-32. doi: 10.1097/GME.0000000000000196
  6. Hitchcock CL, Elliott TG, Norman EG, et al. Hot flushes and night sweats differ in associations with cardiovascular markers in healthy early postmenopausal women. Menopause 2012;19(11):1208-14.
  7. Rendall MJ, Simonds LM, Hunter MS. The Hot Flush Beliefs Scale: a tool for assessing thoughts and beliefs associated with the experience of menopausal hot flushes and night sweats. Maturitas 2008;60(2):158-69.
  8. Writing Group for the Women’s Health Initiative I. Risks and benefits of estrogen plus progestin in health postmenopausal women: prinicpal results from the Women’s Health Initiative Randomized Control trial. JAMA 2002;288:321-33.
  9. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial. JAMA 2004;291(14):1701-12.
  10. Harman SM, Black DM, Naftolin F, et al. Arterial imaging outcomes and cardiovascular risk factors in recently menopausal women: a randomized trial. AnnInternMed 2014;161(4):249-60.
  11. Stampfer MJ, Golditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease. New Engl J Med 1991;325:756-62.
  12. Falkeborn M, Persson I, Adami HO, et al. The risk of acute myocardial infarction after oestrogen and oestrogen-progestogen replacement. Br J Obstet Gynaecol 1992;99(10):821-28.
  13. Prior JC. Postmenopausal estrogen therapy and cardiovascular disease (letter). New Engl J Med 1992;326:705-06.
  14. Thurston RC, Aslanidou Vlachos HE, Derby CA, et al. Menopausal Vasomotor Symptoms and Risk of Incident Cardiovascular Disease Events in SWAN. J Am Heart Assoc 2021;10(3):e017416. doi: 10.1161/JAHA.120.017416 [published Online First: 20210120]
  15. Prior JC, Cameron A, Fung M, et al. Oral micronized progesterone for perimenopausal night sweats and hot flushes a Phase III Canada-wide randomized placebo-controlled 4 month trial. Sci Rep 2023;13(1):9082. doi: https://www.nature.com/articles/s41598-023-35826-w [published Online First: 20230605]
  16. Hale GE, Hitchcock CL, Williams LA, et al. Cyclicity of breast tenderness and night-time vasomotor symptoms in mid-life women: information collected using the Daily Perimenopause Diary. Climacteric 2003;6(2):128-39.
  17. MacLennan AH, Broadbent JL, Lester S, et al. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database SystRev 2004(4):CD002978.
  18. Casper RF, Dodin S, Reid RL, et al. The effect of 20 ug ethinyl estradiol/1 mg norethindrone acetate (Minestrin TM),  a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes, and quality of life in symptomatic perimenopausal women. Menopause 1997;4:139-47.
  19. Prior JC, Hitchcock CL. Progesterone for hot flush and night sweat treatment – effectiveness for severe vasomotor symptoms and lack of withdrawal rebound. GynecolEndocrinol 2012;28 Suppl 2:7-11.
  20. Hitchcock CL, Prior JC. Oral Micronized Progesterone for Vasomotor Symptoms in Healthy Postmenopausal Women–a placebo-controlled randomized trial. Menopause 2012;19:886-93.

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