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Does postmenopausal hormone replacement therapy affect cardiac autonomic regulation in osteoporotic women?

Niskanen, Leo MD1; Laitinen, Tomi MD2; Tuppurainen, Marjo MD3; Saarikoski, Seppo MD3; Kröger, Heikki MD4; Alhava, Esko MD4; Hartikainen, Juha MD1


Objective Postmenopausal hormone replacement therapy (HRT) has been associated with reduced risk of cardiovascular disease; however, the mechanisms remain obscure, and it is not known whether this applies to regimens containing both estrogen and progestin. One possibility is that estrogen would act via enhancement of cardiac autonomic regulation.

Design In this prospective, controlled study of 6-months duration, 22 osteoporotic, postmenopausal women in the intervention group were treated with combined estradiol hemihydrate corresponding to estradiol 2 mg and norethisterone acetate 1 mg with or without clodronate (HRT group). Nine women in the control group received clodronate only. Indices of heart rate variability (HRV) by power spectral analyses and baroreceptor sensitivity (BRS) by phenylephrine test were measured before and after 3 and 6 months of treatment.

Results The total power of HRV remained identical within the groups, although it was higher at 3 and 6-month measurements in the control group than the HRT group. This was mainly due to lower very low frequency and high frequency power in the HRT group. However, no changes in the low frequency/high frequency-ratio of HRV, an index of sympathovagal balance, were observed between and within the groups. Further, during the intervention, no significant changes in BRS (baseline and 6 months: 5.0 ± 2.1 and 5.1 ± 2.5 ms/mmHg) within the HRT group was observed.

Conclusions The impact of estrogen and progesterone on cardiac autonomic regulation seems to be quite modest. Therefore, cardiac morbidity and mortality are probably not mediated by their effects on cardiac autonomic regulation. However, the effects of estrogen alone or more selective estrogen receptor modulators need yet to be clarified in future studies.

From the 1 Department of Medicine, 2 Department of Clinical Physiology, 3 Department of Obstetrics and Gynecology, and 4 Department of Surgery, Kuopio University Hospital, Kuopio, Finland.

Received April 30, 2001;

revised and accepted July 24, 2001.

Address reprint requests to Leo Niskanen, MD, Associate Professor, Department of Medicine, Building Number 5, Kuopio University Hospital, PO Box 1777, FIN-70211 Kuopio, Finland. E-mail:

©2002The North American Menopause Society