Effect of hot flushes on vascular function: a randomized controlled trial.
OBJECTIVE
To compare the vascular responses to hormone therapy in women with and without hot flushes.


METHODS
We randomly assigned 143 healthy, recently postmenopausal women (mean age 52.4+/-0.2 years, time since menopause 19.5+/-0.9 months) with intolerable hot flushes (more than seven moderate/severe episodes per day) or tolerable hot flushes (fewer than three mild episodes per day) to receive 1 mg of transdermal estradiol gel, oral estradiol (2 mg) with and without daily medroxyprogesterone acetate, or placebo for 6 months. Vascular function was assessed by pulse-wave analysis and endothelial function testing with nitroglycerin and salbutamol challenges.


RESULTS
Hot flushes did not affect the changes in arterial or aortic stiffness or endothelial function in response to various forms of hormone therapy. However, in women with tolerable hot flushes, oral estradiol caused a decrease of 13.2% (P=.028) in the time to the first systolic peak (dependent on the rapid phase of ventricular ejection) after nitroglycerin. In addition, the time to the reflected wave (dependent on pulse-wave velocity) after nitroglycerin was decreased by 8.4% (P=.018). These effects were not seen in women with intolerable hot flushes or with the other treatment regimens.


CONCLUSIONS
Women without troublesome hot flushes are susceptible to unfavorable vascular effects after oral estrogen treatment, resulting in less compliant vasculature.


BACKGROUND
ClinicalTrials.gov, www.clinicaltrials.gov, NCT00668603.


METHODS
I.
Tuomikoski
Pauliina
P
From the Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Folkhälsan Institute of Genetics, Folkhälsan Research Center, Biomedicum Helsinki, Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, and Division of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki, Finland.
Ebert
Pia
P
Groop
Per-Henrik
PH
Haapalahti
Petri
P
Hautamäki
Hanna
H
Rönnback
Mats
M
Ylikorkala
Olavi
O
Mikkola
Tomi S
TS
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000420:Albuterol; D004730:Endothelium, Vascular / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D019584:Hot Flashes / Q000503:physiopathology*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage; D008875:Middle Aged; D005996:Nitroglycerin; D011673:Pulsatile Flow / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects*
D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D005996:Nitroglycerin; D000420:Albuterol