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Obesity and fat distribution in relation to hot flashes in Dutch women from the DOM-project
JOURNAL OF THE CLMACTERIC & POSTMENOPAUSE
Maturitas 23 (1996) 301-305
Obesity and fat distribution in relation to hot flashes in Dutch women from the DOM-project I. den Tonkelaa+*,
J.C. Seidellb, P.A.H. van Noorda
“Department of Epidemiology, University of Utrecht, PO Box 80035, 3508 TA Utrecht, The NetherlanA bDepartment of Chronic Disease and Environmental Epidemiology, National Institute of Public Health and Environmenral Protection, Bilthoven, The Netherlands
Received 7 August 1995; accepted 22 November1995
Abstract
The authors studiedobesity and fat distribution in relation to the occurrenceof hot flashesin a population-based study comprising2904womenaged40-44 and 569womenaged54-69 presentingfor mammographicscreening(the DOM-project). Women aged40-44 in the upper tertiles of Quetelet’sindex and waist/hip ratio reported hot flashes significantly more often than women in the respectivelower tertiles. Theseassociationswere independentof each other and independentof age. After adjustment for age, waist/hip ratio and menopausalstatus, the odds ratio comparing the upper tertile of Quetelet’sindex to the lower tertile was 1.70 (95% confidenceinterval, 1.30-2.21). After adjustment for age, Quetelet’sindex and menopausalstatus, the odds ratio comparing the upper tertile of waist/hip ratio to the lower tertile was 1.37 (95% CI, 1.05- 1.78). In women aged 54-69 no significant associations betweenQuetelet’sindex and complaintsof hot flasheswere observed.Women in the upper tertile of waist/hip ratio reported hot flashesmore often than womenin the lower tertile, but this result wasnot significant(OR 1.38;95% CI, 0.87-2.22). Keywords:
Obesity; Fat distribution; Hot flashes;Climacteric; Menopause
1. Introduction In a study by Erlik et al. it postmenopausal women of about with severe hot flashes were less to asymptomatic women [I]. In this association might be different * Corresponding
author.
was found that 50 years of age obese compared younger women because obesity
can lead to earlier ovarian insufficiency [Z]. To our knowledge the association between fat distribution and hot flashes has not been reported previously. We therefore investigated the relation between the degree of obesity and fat distribution on the one hand and reported occurrence of hot flashes on the other hand in women aged 40-44 and in women aged 54-69 presenting for routine mammographic screening.
0378-5122/96/$15.00 0 1996 Elsevier Science B.V. All rights reserved SSDZ 0378-5122(95)00990-3
302
I. den Tonkeluar
et al. i MaturiIas
2. Subjects and methods 2. I Measurements and data collection The women studied were 3273 participants aged 40-44 (younger age group) and 601 participants aged 54-69 (older age group) in a population-based breast cancer screening project, the DOM-project in Utrecht, the Netherlands. The design and methodology of the DOM-project have been described previously [3]. Anthropometric measurements of these women were performed by trained assistants from 1984 through 1986. Body weight was measured to the nearest 0.1 kg. Body height was measured to the nearest 0.1 cm. Quetelet’s index (QI) was calculated as weight divided by height squared (kg/m2). Waist girth was measured to the nearest 0.5 cm at the minimum circumference. Hip circumference was measured to the nearest 0.5 cm at the widest point of the hip area. Waist/hip ratio (WHR) was calculated as waist girth divided by hip circumference. These women are part of a larger screened population that has been described previously with respect to reproductive characteristics, smoking behaviour, some chronic diseases and the anthropometric characteristics mentioned [4,5]. Women were asked to report the occurrence of hot flashes by self-administered questionnaire. Women in the younger age group were asked: “Did you have hot flashes in the preceding year? (sudden blushing and glowing): yes/no”. Women in the older age group were asked: “Do you have hot flashes, and if so, since which year”. Only the year was coded. If a year was coded the woman was categorised as having flashes. Menopausal status and type of menopause were classified in four categories: premenopausal, natural menopause (menstruations had stopped spontaneously more than 12 months before), hysterectomized (uterus and/or one of the ovaries removed) and ovariectomized (both ovaries removed). Menopausal status was unknown in four women of the younger age group and in one woman of the older age group. Women using oral contraceptives or with
23 (1996)
301-305
missing data for this variable (n = 348 and n = 16, respectively, in the younger age group) and women using drugs for menopausal complaints or with missing data for this variable (n = 28 and n = 4 respectively, in the older age group) were excluded from all analyses. Five women in the younger age group had missing data for hot flashes. The resulting number of women left for the analyses was 2904 for the younger age group and 569 for the older age group. 2.2. Statistical
methods
Statistical analyses were performed using SPSSX [6]. Multiple logistic regression was used in order to determine adjusted odds ratios (OR) in tertiles of QI and WHR. The odds ratio is a measure of association. Tertiles (three groups with equal numbers) were used in order to be able to compare the odds ratios for QI with the odds ratios for WHR. Age was classified into two years categories.
3. Results Table 1 shows the prevalence of hot flashes according to menopausal status and type of menopause for the younger and the older age group respectively. Table 2 shows that in the younger age group after adjustment for age both QI and WHR were positively associated with hot flashes. When QI and WHR were also adjusted for each other both were still significantly associated with Additional for hot flashes. adjustment menopausal status resulted in somewhat lower odds patios. Tests for linear trend in the multivariate analyses were significant (P < 0.0001 for QI and P < 0.02 for WHR). Table 3 shows that in the older age group QI was not significantly associated with hot flashes. There was a tendency for a positive association between WHR and hot flashes, but after adjustment for age, QI and menopausal status the odds ratios comparing the middle and the upper
I. den Tonkelaar
et al. 1 Maturitas
23 (1996)
303
301-305
Table 1 Prevalence of hot flashes in women according to menopausal status Status
Premenopausal Postmenopausal Natural Hysterectomized Ovariectomized Total
Women aged 40-44
Women aged 54-69
Number
Hot flashes (%)
2324
15.1
26
50.0
164 379 33 2900
19.5 30.9 60.6 18.0
413 16 53 568
33.2 26.3 28.3 32.5
tertile of WHR to the lower tertile were not significantly different from one and the test for linear trend was not significant.
4. Discussion
A new observation in this study is that WHR and QI independently of each other were positively related to the prevalence of hot flashes in women aged 40-44. This finding seems to be in contrast with the results of a study by Erlik et al. PI, who observed that postmenopausal women with severe hot flashes had significantly lower mean body weight and percent ideal weight than women without hot flashes. The observed lower circulating levels of estrone, estradiol and non-SHBG-bound estradiol (not bound to sex-hormone binding globuline) in women with lower body weight were proposed to explain the inverse association between degree of overweight and hot flashes. Climacteric symptoms such as hot flashes are thought to be primarily an effect of estrogen deficiency [1,7,8]. Although women with normal or very high estrogen levels can experience hot flashes [9,10]. Postmenopausal obese women have increased estrogen production in comparison to non-obese women [l 1,121 and higher levels of non-SHBGbound estradiol [ 131. Postmenopausal obese women would therefore suffer less from climacteric symptoms. The prevalence of obesity, however, was found to be significantly increased among women that present with menopausal complaints [14]. Klinga et al. reported that in
Number
Hot flashes (‘Y
obese women the climacteric onset of increased FSH production and decreased estrogen concentration is about 4 years earlier compared to non-obese women [2]. Ovarian insufficiency would therefore occur earlier in obese women. This is compatible with our finding that in women aged 40-44 years obese women report hot flashes more often compared to non-obese women. In the older group (aged 54-69 years) no significant association between QI and WHR and the occurrence of hot flashes was observed (Table 3) suggesting that this association is only present in the early phases of the climacteric. The absence of a significant positive association between fat distribution and hot flashes in the older age group might be due to small numbers. After adjustment for age, QI and menopausal status, the odds ratios were similar to those in the younger age group. In summary, we found that in a healthy population of Dutch women aged 40-44 years, obesity and abdominal fat distribution were independently of age and each other positively related to the occurrence of hot flashes. Further studies are needed to clarify the association between fat distribution and hot flashes in older women.
Acknowledgements
The Authors wish to thank Professor Dr F. De Waard, Professor Dr H.J.A. Collette. and Professor Dr E.R. te Velde for helpful comments.
840 (86.9) 800 (82.6) 742 (76.7)
833 (86.1) 797 (82.3) 752 (77.6)
127 (13.1) 169 (17.4) 226 (23.3)
134 (13.9) 171 (17.7) 217 (22.4)
No (n (%))
1.00 1.33 (1.04-1.70) 1.79 (1.41-2.27)
1.00 1.40 (1.09-1.79) 2.01 (1.59-2.56) 1.00 1.34 (1.05-1.71) 1.79 (1.41-2.27)
1.00 1.39 (1.08-1.78) 2.02 (1.59-2.56)
1.00 1.28 (0.99-1.66) 1.70 (1.30-2.21) 1.00 1.20 (0.93-1.55) 1.37 (1.05-1.78)
1.00 1.31 (1.02-1.69) 1.76 (1.36-2.28) 1.00 1.23 (0.96- 1.58) 1.44 (1.11-1.86)
< 24.47 24.47-27.31 227.32 WHR <0.753 0.753-0.801 20.802
QI
Tertiles
128 (67.7) 122 (63.9) 134 (70.9)
135 (71.1) 126 (66.3) 123 (65.1)
55 (28.9) 64 (33.7) 66 (34.9)
No (n (%))
61 (32.3) 69 (36.1) 55 (29.1)
Yes (n (%))
Flashes
1.00 1.25 (0.81-1.93) 1.32 (0.85-2.03)
1.00 1.19 (0.78-1.81) 0.86 (0.56- 1.33)
Unadjusted OR (95% CI)
1.00 1.25 (0.80- 1.96) 1.33 (0.85-2.07)
1.00 1.27 (0.82-1.96) 0.92 (0.59-I 44)
Age adjusted OR (95% CI)
1.00 I .26 (0.80- 1.97) 1.41 (0.89-2.26)
1.00 1.20 (0.77- 1.87) 0.83 (0.52- 1.33)
Age and QI or WHR adjusted OR (95% CI)
1.00 1.25 1.38 ~~-.
(0.79 1.96) (0.87 2.22) -.-. ~
1.00 1.19 (0.76-1.85) 0.85 (0.52- 1.36)
Age, menopausal status and QI or WHR adjusted OR (95% CI)
Table 3 Association of hot flashes with QI and WHR expressed as odds ratios with 95% confidence intervals (CI), comparing the middle and upper tertile to the lower tertile, in 569 women aged 54-69
22.49-25.34 ~25.35 WHR <0.731 0.731-0.777 20.778
QI < 22.49
Yes (n (%))
Table 2 Association of hot flashes with QI and WHR expressed as odds ratios with 95% confidence intervals (CI), comparing the middle and upper tertile to the lower tertile. in 2904 women aged 40-44 ^ .___~ Tertiles Flashes Unadjusted OR (95% CI) Age and QI or WHR Age adjusted OR (95% CI) Age, menopausal adjusted OR (95% CI) status and QI or WHR adjusted OR (95% CI)
I. den Tonkelaar
et al. / Maturitas
23 (1996)
References [l] Erlik Y, Meldrum DR, Judd HL. Estrogen levels in postmenopausal women with hot flashes. Obstet Gynecol 1982; 59: 403-407. [2] Klinga K, Von Holst T, Runnebaum B. Influence of severe obesity on peripheral hormone concentrations in pre- and postmenopausal women. Eur J Obstet Gynecol Reprod Biol 1983; 15: 103-112. [3] Waard de F, Collette HJA, Rombach JJ, Baanders-van Halewijn EA, Honing C. The DOM-project for the early detection of breast cancer. J Chron Dis 1984; 37: l-44. [4] Tonkelaar den I, Seidell JC, Noord van PAH, Baandersvan Halewijn EA, Ouwehand IJ. Fat distribution in relation to age, degree of obesity, smoking habits, parity and estrogen use - a cross-sectional study in 11825 Dutch women participating in the DOM-project. Int J Obesity 1990; 14: 753-761. [5] Noord van PAH, Seidell JC, Tonkelaar den I, Baandersvan Halewijn EA, Ouwehand IJ. The relationship between fat distribution and some chronic diseases in 11825 women participating in the DOM-project. Int J Epidemiology 1990; 19: 564570. [6] SPSS-X, 2nd ed, New York, McGraw-Hill, 1986. [7] Mahesh. Gonadotrophins in the menopause. In: Keep PA
[8] [9]
[lo]
[I l] [12] [13]
[14]
301-305
305
van, Greenblatt RB, Albeaux-Fernet M, eds. Consensus on menopause Research. MTP, Lancaster, England 1976; 11-18. Kronenberg F. Hot flashes: epidemiology and physiology. Ann New York Acad Sci 1990; 592: 53-86. Bider D, Ben-Rafael Z, Shalev J, Mashiach S,‘Serr DM, Blankstein J. Hot flushes during Gn-RH analogue administration despite normal serum oestradiol levels. Maturitas 1989: 11: 223-228 Gangar K, Cust M, Whitehead Ml. Symptoms of oestrogen deficiency associated with supraphysiological plasma oestradiol concentrations in women with oestradiol implants. Br Med J 1989; 299: 601-602 Grodin JM, Siiteri PK, McDonald PC. Source of esterone production in postmenopausal women. J Clin Endocrinol Metab 1973; 36: 207-214. Waard de F, Baanders-van Halewijn EA. Cross-sectional data on estrogenic smears in a postmenopausal population. Acta Cytol 1969: 13: 6755678. Ota DM, Jones LA, Jackson G, Jackson P, Kemp K, Bauman D. Obesity, non-protein bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients. Cancer 1986; 57: 558-562. Anderson E, Hamburger S, Liu JH, Rebar RW. Characteristics of menopausal women seeking assistance. Am J Obstet Gynecol 1987; 156: 4288433.
Maturitas 23 (1996) 301-305
Obesity and fat distribution in relation to hot flashes in Dutch women from the DOM-project I. den Tonkelaa+*,
J.C. Seidellb, P.A.H. van Noorda
“Department of Epidemiology, University of Utrecht, PO Box 80035, 3508 TA Utrecht, The NetherlanA bDepartment of Chronic Disease and Environmental Epidemiology, National Institute of Public Health and Environmenral Protection, Bilthoven, The Netherlands
Received 7 August 1995; accepted 22 November1995
Abstract
The authors studiedobesity and fat distribution in relation to the occurrenceof hot flashesin a population-based study comprising2904womenaged40-44 and 569womenaged54-69 presentingfor mammographicscreening(the DOM-project). Women aged40-44 in the upper tertiles of Quetelet’sindex and waist/hip ratio reported hot flashes significantly more often than women in the respectivelower tertiles. Theseassociationswere independentof each other and independentof age. After adjustment for age, waist/hip ratio and menopausalstatus, the odds ratio comparing the upper tertile of Quetelet’sindex to the lower tertile was 1.70 (95% confidenceinterval, 1.30-2.21). After adjustment for age, Quetelet’sindex and menopausalstatus, the odds ratio comparing the upper tertile of waist/hip ratio to the lower tertile was 1.37 (95% CI, 1.05- 1.78). In women aged 54-69 no significant associations betweenQuetelet’sindex and complaintsof hot flasheswere observed.Women in the upper tertile of waist/hip ratio reported hot flashesmore often than womenin the lower tertile, but this result wasnot significant(OR 1.38;95% CI, 0.87-2.22). Keywords:
Obesity; Fat distribution; Hot flashes;Climacteric; Menopause
1. Introduction In a study by Erlik et al. it postmenopausal women of about with severe hot flashes were less to asymptomatic women [I]. In this association might be different * Corresponding
author.
was found that 50 years of age obese compared younger women because obesity
can lead to earlier ovarian insufficiency [Z]. To our knowledge the association between fat distribution and hot flashes has not been reported previously. We therefore investigated the relation between the degree of obesity and fat distribution on the one hand and reported occurrence of hot flashes on the other hand in women aged 40-44 and in women aged 54-69 presenting for routine mammographic screening.
0378-5122/96/$15.00 0 1996 Elsevier Science B.V. All rights reserved SSDZ 0378-5122(95)00990-3
302
I. den Tonkeluar
et al. i MaturiIas
2. Subjects and methods 2. I Measurements and data collection The women studied were 3273 participants aged 40-44 (younger age group) and 601 participants aged 54-69 (older age group) in a population-based breast cancer screening project, the DOM-project in Utrecht, the Netherlands. The design and methodology of the DOM-project have been described previously [3]. Anthropometric measurements of these women were performed by trained assistants from 1984 through 1986. Body weight was measured to the nearest 0.1 kg. Body height was measured to the nearest 0.1 cm. Quetelet’s index (QI) was calculated as weight divided by height squared (kg/m2). Waist girth was measured to the nearest 0.5 cm at the minimum circumference. Hip circumference was measured to the nearest 0.5 cm at the widest point of the hip area. Waist/hip ratio (WHR) was calculated as waist girth divided by hip circumference. These women are part of a larger screened population that has been described previously with respect to reproductive characteristics, smoking behaviour, some chronic diseases and the anthropometric characteristics mentioned [4,5]. Women were asked to report the occurrence of hot flashes by self-administered questionnaire. Women in the younger age group were asked: “Did you have hot flashes in the preceding year? (sudden blushing and glowing): yes/no”. Women in the older age group were asked: “Do you have hot flashes, and if so, since which year”. Only the year was coded. If a year was coded the woman was categorised as having flashes. Menopausal status and type of menopause were classified in four categories: premenopausal, natural menopause (menstruations had stopped spontaneously more than 12 months before), hysterectomized (uterus and/or one of the ovaries removed) and ovariectomized (both ovaries removed). Menopausal status was unknown in four women of the younger age group and in one woman of the older age group. Women using oral contraceptives or with
23 (1996)
301-305
missing data for this variable (n = 348 and n = 16, respectively, in the younger age group) and women using drugs for menopausal complaints or with missing data for this variable (n = 28 and n = 4 respectively, in the older age group) were excluded from all analyses. Five women in the younger age group had missing data for hot flashes. The resulting number of women left for the analyses was 2904 for the younger age group and 569 for the older age group. 2.2. Statistical
methods
Statistical analyses were performed using SPSSX [6]. Multiple logistic regression was used in order to determine adjusted odds ratios (OR) in tertiles of QI and WHR. The odds ratio is a measure of association. Tertiles (three groups with equal numbers) were used in order to be able to compare the odds ratios for QI with the odds ratios for WHR. Age was classified into two years categories.
3. Results Table 1 shows the prevalence of hot flashes according to menopausal status and type of menopause for the younger and the older age group respectively. Table 2 shows that in the younger age group after adjustment for age both QI and WHR were positively associated with hot flashes. When QI and WHR were also adjusted for each other both were still significantly associated with Additional for hot flashes. adjustment menopausal status resulted in somewhat lower odds patios. Tests for linear trend in the multivariate analyses were significant (P < 0.0001 for QI and P < 0.02 for WHR). Table 3 shows that in the older age group QI was not significantly associated with hot flashes. There was a tendency for a positive association between WHR and hot flashes, but after adjustment for age, QI and menopausal status the odds ratios comparing the middle and the upper
I. den Tonkelaar
et al. 1 Maturitas
23 (1996)
303
301-305
Table 1 Prevalence of hot flashes in women according to menopausal status Status
Premenopausal Postmenopausal Natural Hysterectomized Ovariectomized Total
Women aged 40-44
Women aged 54-69
Number
Hot flashes (%)
2324
15.1
26
50.0
164 379 33 2900
19.5 30.9 60.6 18.0
413 16 53 568
33.2 26.3 28.3 32.5
tertile of WHR to the lower tertile were not significantly different from one and the test for linear trend was not significant.
4. Discussion
A new observation in this study is that WHR and QI independently of each other were positively related to the prevalence of hot flashes in women aged 40-44. This finding seems to be in contrast with the results of a study by Erlik et al. PI, who observed that postmenopausal women with severe hot flashes had significantly lower mean body weight and percent ideal weight than women without hot flashes. The observed lower circulating levels of estrone, estradiol and non-SHBG-bound estradiol (not bound to sex-hormone binding globuline) in women with lower body weight were proposed to explain the inverse association between degree of overweight and hot flashes. Climacteric symptoms such as hot flashes are thought to be primarily an effect of estrogen deficiency [1,7,8]. Although women with normal or very high estrogen levels can experience hot flashes [9,10]. Postmenopausal obese women have increased estrogen production in comparison to non-obese women [l 1,121 and higher levels of non-SHBGbound estradiol [ 131. Postmenopausal obese women would therefore suffer less from climacteric symptoms. The prevalence of obesity, however, was found to be significantly increased among women that present with menopausal complaints [14]. Klinga et al. reported that in
Number
Hot flashes (‘Y
obese women the climacteric onset of increased FSH production and decreased estrogen concentration is about 4 years earlier compared to non-obese women [2]. Ovarian insufficiency would therefore occur earlier in obese women. This is compatible with our finding that in women aged 40-44 years obese women report hot flashes more often compared to non-obese women. In the older group (aged 54-69 years) no significant association between QI and WHR and the occurrence of hot flashes was observed (Table 3) suggesting that this association is only present in the early phases of the climacteric. The absence of a significant positive association between fat distribution and hot flashes in the older age group might be due to small numbers. After adjustment for age, QI and menopausal status, the odds ratios were similar to those in the younger age group. In summary, we found that in a healthy population of Dutch women aged 40-44 years, obesity and abdominal fat distribution were independently of age and each other positively related to the occurrence of hot flashes. Further studies are needed to clarify the association between fat distribution and hot flashes in older women.
Acknowledgements
The Authors wish to thank Professor Dr F. De Waard, Professor Dr H.J.A. Collette. and Professor Dr E.R. te Velde for helpful comments.
840 (86.9) 800 (82.6) 742 (76.7)
833 (86.1) 797 (82.3) 752 (77.6)
127 (13.1) 169 (17.4) 226 (23.3)
134 (13.9) 171 (17.7) 217 (22.4)
No (n (%))
1.00 1.33 (1.04-1.70) 1.79 (1.41-2.27)
1.00 1.40 (1.09-1.79) 2.01 (1.59-2.56) 1.00 1.34 (1.05-1.71) 1.79 (1.41-2.27)
1.00 1.39 (1.08-1.78) 2.02 (1.59-2.56)
1.00 1.28 (0.99-1.66) 1.70 (1.30-2.21) 1.00 1.20 (0.93-1.55) 1.37 (1.05-1.78)
1.00 1.31 (1.02-1.69) 1.76 (1.36-2.28) 1.00 1.23 (0.96- 1.58) 1.44 (1.11-1.86)
< 24.47 24.47-27.31 227.32 WHR <0.753 0.753-0.801 20.802
QI
Tertiles
128 (67.7) 122 (63.9) 134 (70.9)
135 (71.1) 126 (66.3) 123 (65.1)
55 (28.9) 64 (33.7) 66 (34.9)
No (n (%))
61 (32.3) 69 (36.1) 55 (29.1)
Yes (n (%))
Flashes
1.00 1.25 (0.81-1.93) 1.32 (0.85-2.03)
1.00 1.19 (0.78-1.81) 0.86 (0.56- 1.33)
Unadjusted OR (95% CI)
1.00 1.25 (0.80- 1.96) 1.33 (0.85-2.07)
1.00 1.27 (0.82-1.96) 0.92 (0.59-I 44)
Age adjusted OR (95% CI)
1.00 I .26 (0.80- 1.97) 1.41 (0.89-2.26)
1.00 1.20 (0.77- 1.87) 0.83 (0.52- 1.33)
Age and QI or WHR adjusted OR (95% CI)
1.00 1.25 1.38 ~~-.
(0.79 1.96) (0.87 2.22) -.-. ~
1.00 1.19 (0.76-1.85) 0.85 (0.52- 1.36)
Age, menopausal status and QI or WHR adjusted OR (95% CI)
Table 3 Association of hot flashes with QI and WHR expressed as odds ratios with 95% confidence intervals (CI), comparing the middle and upper tertile to the lower tertile, in 569 women aged 54-69
22.49-25.34 ~25.35 WHR <0.731 0.731-0.777 20.778
QI < 22.49
Yes (n (%))
Table 2 Association of hot flashes with QI and WHR expressed as odds ratios with 95% confidence intervals (CI), comparing the middle and upper tertile to the lower tertile. in 2904 women aged 40-44 ^ .___~ Tertiles Flashes Unadjusted OR (95% CI) Age and QI or WHR Age adjusted OR (95% CI) Age, menopausal adjusted OR (95% CI) status and QI or WHR adjusted OR (95% CI)
I. den Tonkelaar
et al. / Maturitas
23 (1996)
References [l] Erlik Y, Meldrum DR, Judd HL. Estrogen levels in postmenopausal women with hot flashes. Obstet Gynecol 1982; 59: 403-407. [2] Klinga K, Von Holst T, Runnebaum B. Influence of severe obesity on peripheral hormone concentrations in pre- and postmenopausal women. Eur J Obstet Gynecol Reprod Biol 1983; 15: 103-112. [3] Waard de F, Collette HJA, Rombach JJ, Baanders-van Halewijn EA, Honing C. The DOM-project for the early detection of breast cancer. J Chron Dis 1984; 37: l-44. [4] Tonkelaar den I, Seidell JC, Noord van PAH, Baandersvan Halewijn EA, Ouwehand IJ. Fat distribution in relation to age, degree of obesity, smoking habits, parity and estrogen use - a cross-sectional study in 11825 Dutch women participating in the DOM-project. Int J Obesity 1990; 14: 753-761. [5] Noord van PAH, Seidell JC, Tonkelaar den I, Baandersvan Halewijn EA, Ouwehand IJ. The relationship between fat distribution and some chronic diseases in 11825 women participating in the DOM-project. Int J Epidemiology 1990; 19: 564570. [6] SPSS-X, 2nd ed, New York, McGraw-Hill, 1986. [7] Mahesh. Gonadotrophins in the menopause. In: Keep PA
[8] [9]
[lo]
[I l] [12] [13]
[14]
301-305
305
van, Greenblatt RB, Albeaux-Fernet M, eds. Consensus on menopause Research. MTP, Lancaster, England 1976; 11-18. Kronenberg F. Hot flashes: epidemiology and physiology. Ann New York Acad Sci 1990; 592: 53-86. Bider D, Ben-Rafael Z, Shalev J, Mashiach S,‘Serr DM, Blankstein J. Hot flushes during Gn-RH analogue administration despite normal serum oestradiol levels. Maturitas 1989: 11: 223-228 Gangar K, Cust M, Whitehead Ml. Symptoms of oestrogen deficiency associated with supraphysiological plasma oestradiol concentrations in women with oestradiol implants. Br Med J 1989; 299: 601-602 Grodin JM, Siiteri PK, McDonald PC. Source of esterone production in postmenopausal women. J Clin Endocrinol Metab 1973; 36: 207-214. Waard de F, Baanders-van Halewijn EA. Cross-sectional data on estrogenic smears in a postmenopausal population. Acta Cytol 1969: 13: 6755678. Ota DM, Jones LA, Jackson G, Jackson P, Kemp K, Bauman D. Obesity, non-protein bound estradiol levels, and distribution of estradiol in the sera of breast cancer patients. Cancer 1986; 57: 558-562. Anderson E, Hamburger S, Liu JH, Rebar RW. Characteristics of menopausal women seeking assistance. Am J Obstet Gynecol 1987; 156: 4288433.