1 Department of Obstetrics and Gynaecology, PO Box 140, 2 Department of Medicine, Division of Geriatrics, PO Box 340, and 3 Department of Clinical Chemistry, PO Box 360, Helsinki University Central Hospital, FIN-00029 HYKS, Finland
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Abstract |
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Key words: hormone replacement therapy/leptin/menopause
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Introduction |
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Conflicting data exist on the effect of oral hormone replacement therapy (HRT) on leptin in postmenopausal women (Kohrt et al., 1966; Castracane et al.1998;
Elbers et al.1999
, Di Carlo et al.2000
). Presently, oral HRT and transdermal HRT compete for favour in clinical practice. Due to the lacking first pass liver metabolism of transdermal HRT, responses in the circulating lipids, lipoproteins, and various binding proteins differ in users of oral and transdermal HRT (Hänggi et al.1997
). Therefore, we compared the long-term effects of oral and transdermal oestradiol plus norethisterone acetate administration on the plasma leptin concentrations in healthy postmenopausal women.
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Materials and methods |
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The leptin data were skewed and were therefore log transformed before analyses. The data (presented as mean ± SEM) were analysed by two-way analysis of variance (ANOVA) with repeated measurements. When indicated by ANOVA, the significance at individual time points was calculated using the t-test for independent means (between group comparison), or the t-test for dependent means (comparison with baseline within a single group). Pearson's correlation was used for correlation analyses. A power calculation showed that this population was large enough to detect a 15% change in leptin with 87% power at a P-level of 0.05.
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Results |
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Baseline plasma leptin, ranging from 3.3 to 34.9 µg/l, was similar in both groups and was significantly associated with BMI (r = 0.78, P < 0.0001
). Oestradiol + NETA, as a whole, or as considered either as an oral or transdermal regimen separately, failed to affect the plasma leptin concentration or BMI (Table II). Individual (and insignificant) changes in body weight and those in plasma leptin at each study point were not related to each other.
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Discussion |
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The plasma leptin concentration is co-dependent on leptin synthesis by the adipocytes (
Zhang et al.1994) and renal clearance of leptin (
Cumin et al.1997
). Because HRT, as a whole, or oestradiol + NETA do not alter renal function, any change in plasma leptin concentration observed during oestradiol + NETA may primarily be a reflection of the change in synthesis and release of leptin. Neither oral nor transdermal sequential oestradiol + NETA affected plasma leptin in our subjects. Thus, we can conclude that this combination did not affect the synthesis or release of leptin in our group of postmenopausal women. The lack of an effect of oestradiol + NETA on leptin was a surprise because natural progesterones stimulate leptin release in oestrogen-primed women (
Hardie et al.1997
;
Messinis et al.1998
,2000
). We did not have a control group using placebo, and therefore the impact on leptin of age over the 12 months of the study remains unknown. However, leptin has shown no age dependence in some studies (
Saad et al.1997
;
Sumner et al.1998
), and therefore the lack of a control group is unlikely to invalidate our conclusions.
Our findings should be interpreted with caution. We collected plasma samples during oestradiol + NETA phase, and therefore our data do not exclude the possibility that leptin concentrations could have shown a rise during the oestradiol-only phase of HRT and that NETA could have negated this effect. This is supported by the androgenic activity of NETA, and by data demonstrating that androgens decrease leptin secretion (
Elbers et al.1997). Moreover, our data do not tell anything of the effect of other HRT regimens containing different oestrogens and/or progestins on leptin. HRT can also involve the use of natural progesterone, and its impact on leptin in postmenopausal women is of interest, because natural progesterone stimulates leptin in women immediately after oophorectomy (
Messinis et al.1999
,2000
).
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Acknowledgements |
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Notes |
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5 To whom correspondence should be addressed. E-mail: olavi.ylikorkala{at}hus.fi
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References |
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Submitted on January 29, 2001; accepted on April 4, 2001.