Changes in Serum Leptin Levels during GnRH Agonist Therapy

Abstract

The purpose of the present study was to investigate changes in serum leptin levels during GnRH agonist therapy. Twenty regularly menstruating women with uterine leiomyomas were enrolled. These subjects were given GnRH agonist (leuprorelin acetate, 3.75 mg) monthly for 4 months. Serum leptin and estradiol (E2) levels were measured at the two time points of day 1 or 2 of the menstrual cycle and the end of GnRH agonist therapy. Weight, total body fat mass, percentage of body fat, and total body lean mass were measured by whole body scanning with dual-energy X-ray absorptiometry. The ratio of serum leptin levels to total body fat mass (leptin-fat mass ratio), and the ratio of serum leptin levels to total body lean mass (leptin-lean mass ratio) were calculated. All subjects became amenorrheic after the initial administration of GnRH agonist. Baseline E2 levels were 45.4 +/- 21.0 pg/mL, which significantly decreased after GnRH agonist therapy (13.3 +/- 4.2 pg/mL, p<0.01). Baseline leptin levels were 8.7 +/- 8.1 ng/mL, which did not differ from the values after 4 months of GnRH agonist administration (8.9 +/- 6.8 ng/mL). Total body fat mass significantly increased from 20.0 +/- 10.4 to 21.0 +/- 9.4 kg (p<0.05), while total body lean mass significantly decreased (34.5 +/- 4.2 kg to 33.3 +/- 3.9 kg, p<0.01). However, leptin-fat mass ratio after GnRH agonist therapy did not differ from the baseline values (0.39 +/- 0.16 ng/mL/kg vs 0.38 +/- 0.16 ng/mL/kg). Hypogonadism does not have a major impact on circulating leptin levels.

Body composition and bone mineral density after ovarian hormone suppression with or without estradiol treatment

“…In support of our hypotheses, we observed that ovarian hormone suppression resulted in decreases in FFM and lumbar spine and proximal femur BMD that were prevented by E 2 add-back therapy. Unexpectedly, we did not find an increase in FM in response to GnRH AG +PL, as has been observed by others, 2,3,5,6 but there was an increase in abdominal adiposity as measured by CT.…”

“…2,3,5,6,22 Previous studies included women with uterine leiomyoma, 2,3,5,6,22 or endometriosis. 5 All of these studies found increases in FM and decreases in FFM although not all changes were statistically significant.…”

“…2,3,5,6 However, because none of the previous studies included E 2 add-back therapy, it was not clear whether the decline in FFM was related to the suppression of estrogens or androgens by GnRH AG . In the current study, there were similar nonsignificant decreases in serum testosterone concentration in both the GnRH AG +PL and GnRH AG +E 2 groups, but FFM was decreased only in the former.…”

“…20,21 Less well known is whether E 2 deficiency triggers a decline in lean tissue other than bone, such as skeletal muscle. The suppression of ovarian function in premenopausal women has been observed to result in a decline in fat-free mass (FFM) in some studies, 2,3,5,6 but it is not clear whether this is specifically related to the decline in serum E 2 concentration.…”

Visceral fat accumulation

“…The authors also document a decrease in fat-free mass (FFM), a change seen in some studies. [9][10][11][12] This is also an important observation as FFM determines metabolic rate 13 and, thus, is an important factor in the propensity to gain weight. Because this tissue, which consists primarily of skeletal muscle, diminishes, 13 caloric utilization decreases and adiposity may ensue.…”