A C TA Obstetricia et Gynecologica

AOGS M A I N R E SE A RC H A R TI C LE

Postmenopausal hot flushes and bone mineral density: a longitudinal study PAULIINA TUOMIKOSKI1, OLAVI YLIKORKALA1 & TOMI S. MIKKOLA1,2 Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, and 2Folkha€lsan Research Center, Helsinki, Finland

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Key words Vasomotor symptoms, menopause, osteoporosis, dual-energy X-ray absorptiometry, DXA Correspondence Tomi S. Mikkola, Department of Obstetrics and Gynecology, Helsinki University Central Hospital, PO Box 140, 00029 HUS Helsinki, Finland. E-mail: [email protected] Conflict of interest The authors have stated explicitly that there are no conflicts of interest in connection with this article. Please cite this article as: Tuomikoski P, Ylikorkala O, Mikkola TS. Postmenopausal hot flushes and bone mineral density: a longitudinal study. Acta Obstet Gynecol Scand 2015; 94: 198–203. Received: 15 May 2014 Accepted: 20 November 2014 DOI: 10.1111/aogs.12546

Abstract Objective. To study the possible association between menopausal hot flushes and bone mineral density. Design. Observational study. Setting. University clinic. Population. Healthy women (n = 143) with or without hot flushes, 6–36 months postmenopausal after participating in a 6-month hormone therapy trial. Methods. The women prospectively recorded the number and severity of hot flushes for 2 weeks. Bone mineral density in lumbar and hip bones was measured with dual-energy X-ray absorptiometry at recruitment and reassessed in 114 women approximately 6.2 years later. Main outcome measures. Hot flushes and bone mineral density. Results. At recruitment, hot flushes were absent in 22 women, mild in 32, moderate in 28, and severe in 61. Lumbar bone mineral densities in non-flushing women (1.130  0.022 g/cm2; mean  SEM), and in those with mild (1.088  0.024 g/cm2), moderate (1.082  0.030 g/cm2) or severe (1.102  0.019 g/cm2) hot flushes did not differ, nor were there differences in hip bone mineral densities between the four study groups. During the follow-up, lumbar bone mineral density decreased by a mean of 0.4  0.1% a year in women not using hormone therapy, and increased by 0.1  0.2% a year in hormone therapy users (p = 0.019). The respective non-significant changes in left and right total hip bone mineral densities were – 0.6  0.01 and 1.0  0.1 for the non-users, and 0.4  0.1 and 0.6  0.2 for hormone therapy users. These changes in bone mineral density bore no relation to the hot flush status at baseline. Conclusion. In recently menopausal women, hot flushes do not appear to determine bone mass density. BMD, bone mineral density; BMI, body mass index; DXA, dualenergy X-ray absorptiometry; HFWWS, Hot Flush Weekly Weighted Score; HT, hormone therapy.

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induces elevations in BMD in postmenopausal women (4). On the other hand, hypoestrogenism is also a key factor as regards hot flushes, evidently through effects on

Introduction Bone mineral density (BMD) decreases by 1–2% in the spine and hips each year over several postmenopausal years (1,2). This is mainly due to hypoestrogenism, since circulating estrogens both prevent bone loss and promote bone formation (3). A role for estrogens in bone health is further supported by hormone therapy (HT), which

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Key Message Hot flushes in recently postmenopausal women do not appear to be a determinant of bone mass density.

ª 2014 Nordic Federation of Societies of Obstetrics and Gynecology, Acta Obstetricia et Gynecologica Scandinavica 94 (2015) 198–203

P. Tuomikoski et al.

hypothalamic thermoregulation (5). Recent epidemiological data have implied that hot flushes may serve as independent determinants of bone density (6–11) and may even predict future bone loss (12). The mechanism for such an effect is not known but it may be mediated through the sympathetic nervous system (13). This gains support from data showing that lumbar BMD in perimenopausal women with frequent hot flushes was lower than in non-flushing women (8). Furthermore, since the exact underlying mechanisms behind hot flushes are not known, i.e. why some women have severe hot flushes and some have none, hot flushes could be a marker for sensitivity to hypoestrogenism affecting bone. Interpretation of the data is further complicated, as hot flushes, which show great day-to-day variation, are difficult to assess objectively, and hot flushes recorded retrospectively (6– 9,12,14,15) or during the use of HT (11,12) are inaccurate measures of true hot flush status at the onset of the menopause. We have determined an accurate hot flush status in a carefully selected series of women who entered menopause 6–36 months earlier (16). We now use this patient series to study whether hot flushes in recently postmenopausal women are associated with BMD in the spine and hip and whether hot flush status soon after the onset of menopause predicts changes in BMD after approximately 6 years of follow-up, with or without HT use.

Material and methods Details of recruitment have been reported previously (16). In 2005–2006 through newspaper advertisements we recruited women aged between 48 and 55 years whose last menstrual period had occurred 6–36 months earlier and who were not using any kind of HT. Approximately 1500 women responded. From this group, on the basis of telephone interviews, 400 women were found to fulfil the inclusion criteria: healthy, non-smoking, body mass index (BMI) < 30 kg/m2, no previous HT use. They were invited to our research center and recorded their vasomotor symptoms for 2 weeks with structured written questionnaires. From this sample a final study group of 143 women (see next section “Classification of hot flush severity”) was selected for the present study. Each volunteer showed levels of follicle-stimulating hormone above 30 IU/L, confirming a true postmenopausal state. Other basic laboratory values (such as the levels of thyroid stimulating hormone) were normal, as were findings on pelvic examination (16). To present hot flushes on an objective scale we used the following criteria: a hot flush, defined as a sensation of warmth, with or without concomitant sweating, was rated as mild if there was no sweating or if it did not

Bone mineral density and hot flushes

disturb daily life. A more intense hot flush occurring in daytime, with possible sweating, was rated as moderate. A hot flush with sweating clearly interfering with daily life or sleep, was rated as severe. To get an overall picture of the burden of vasomotor symptoms, a total symptom score was determined. For this score, mild hot flushes were multiplied by 1, moderate flushes by 2, and severe flushes by 3, and the Hot Flush Weekly Weighted Score (HFWWS) was calculated as a sum of these scores (17). We selected 143 women showing either severe, moderate, mild or no hot flushes to participate in our vascular health study (18). In this context BMD (in g/cm2) was also measured in the lumbar spine (vertebrae 1–4) and both hips by dual-energy X-ray absorptiometry (DXA) (Lunar; General Electric, Fairfield, CT, USA). Absorptiometry was calibrated by using a phantom model on each day of examination and variation in BMD readings was

Postmenopausal hot flushes and bone mineral density: a longitudinal study.

To study the possible association between menopausal hot flushes and bone mineral density...
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