Effect of hot flushes on cardiovascular autonomic responsiveness: A randomized controlled trial on hormone therapy

Abstract Objectives To compare the responses of heart rate and blood pressure to various autonomic tests in women with and without pre-treatment hot flushes during estradiol and estradiol + medroxyprogesterone acetate (MPA) use. Study design and main outcome measures Hundred and fifty recently postmenopausal women (72 with and 78 without hot flushes) were randomized to receive transdermal estradiol (1 mg/day), oral estradiol (2 mg/day) alone or in combination with MPA (5 mg/day), or placebo for six months. Cardiovascular responsiveness was comprehensively assessed with controlled and deep breathing, active orthostatic test, Valsalva maneuver and handgrip test. Results Hot flushes were accompanied with a significant reduction (−2.2 ± 0.7 vs. 1.3 ± 1.1 beats/min, p = 0.03) in resting heart rate during estradiol-only treatment; the route of estradiol administration was no factor in this regard. This effect was attenuated by the addition of MPA to oral estradiol. Hot flushes were also associated with reduced maximal heart rate in response to handgrip during the use of estradiol-only therapy (−2.2 ± 1.3 vs. 2.8 ± 1.5 beats/min, p = 0.038); again, the MPA addition eliminated this effect. Hot flushes were accompanied with lowered resting but augmented blood pressure responses to handgrip test during all hormone regimens, whereas in women without hot flushes estradiol-only regimen tended to elevate diastolic resting blood pressure. Conclusions Hot flushes appear as determinants for cardiovascular responses to hormone therapy. Estradiol-only therapy causes beneficial changes in cardiovascular regulation in flushing women, and these are blunted, in part, by the addition of MPA.