Dataset Information

Endogenous sex hormone changes in postmenopausal women in the diabetes prevention program.

ABSTRACT:

Context

Whether endogenous sex hormones (ESH) [SHBG, estradiol, testosterone, and dehydroepiandrosterone (DHEA)] are altered by intensive lifestyle modification (ILS) or metformin and whether such changes affect glucose levels among dysglycemic postmenopausal women is unclear.

Objectives

Our objective was to examine intervention impact on ESH and associations with fasting plasma glucose (FPG) and 2-h glucose changes among postmenopausal glucose-intolerant women.

Design

We performed a secondary analysis of a randomized controlled trial.

Participants

Participants included postmenopausal, overweight, glucose-intolerant women not using exogenous estrogen (n = 382) who participated in the Diabetes Prevention Program.

Interventions

Interventions included ILS with the goals of weight reduction of at least 7% of initial weight and 150 min/wk of moderate intensity exercise or metformin or placebo administered 850 mg twice a day.

Main outcome measures

Intervention-related changes in ESH and associations of changes in ESH and glucose levels were evaluated.

Results

ILS significantly increased SHBG and decreased DHEA before and after adjustment for changes in waist circumference and fasting insulin. ILS did not alter estradiol or testosterone. Metformin did not change any ESH. ILS-induced increases in SHBG and declines in DHEA were associated with decreases in FPG and 2-h glucose, and declines in estradiol were associated with decreases in FPG, before and after adjustment for age, FSH, race/ethnicity, changes in waist circumference, and 1/fasting insulin.

Conclusions

Among postmenopausal glucose-intolerant women not using estrogen, ILS increased SHBG levels and lowered DHEA levels. These changes were associated with lower glucose independent of adiposity and insulin. Metformin effects upon ESH were not significant.

SUBMITTER: Kim C

PROVIDER: S-EPMC3410266 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Endogenous sex hormone changes in postmenopausal women in the diabetes prevention program.

Kim Catherine C Kong Shengchun S Laughlin Gail A GA Golden Sherita H SH Mather Kieren J KJ Nan Bin B Edelstein Sharon L SL Randolph John F JF Labrie Fernand F Buschur Elizabeth E Barrett-Connor Elizabeth E

The Journal of clinical endocrinology and metabolism 20120611 8

<h4>Context</h4>Whether endogenous sex hormones (ESH) [SHBG, estradiol, testosterone, and dehydroepiandrosterone (DHEA)] are altered by intensive lifestyle modification (ILS) or metformin and whether such changes affect glucose levels among dysglycemic postmenopausal women is unclear.<h4>Objectives</h4>Our objective was to examine intervention impact on ESH and associations with fasting plasma glucose (FPG) and 2-h glucose changes among postmenopausal glucose-intolerant women.<h4>Design</h4>We p ...[more]

PMID: 22689695

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Project description:Title: Transcriptome analysis of human endometrial tissues from healthy post-menoupausal women reflecting the endometrial response to 3-weeks treatment with tibolone, E2 and E2+MPA. In an observational, open, non-randomized, controlled study uterine tissues were collected in order to generate endometrial gene expression profiles. healthy postmenopausal women were enrolled into the following treatment groups: Control-group; Tibolone-group, 2,5 mg of tibolone (administered orally) every day, starting 21 days prior to surgery; Estradiol-group, 2 mg of estradiol (administered orally) every day, starting 21 days prior to surgery; Estradiol+progestagen-group, 2 mg of estradiol (administered orally) and 5 mg of MPA (Medroxy Progesteroneacetate, administered orally) every day, starting 21 days prior to surgery. Pure (100%) endometrium was isolated from the snap-frozen uterine tissues and used for RNA isolation. RNA was labeled and hybridized to whole genome Affymetrix U133plus2 GeneChips containing 54,614 probe sets, representing approximately 47,000 transcripts. Relative to the control group, 940 genes are regulated in the endometrium of E2 treated patients, whereas only 198 genes are significantly regulated in endometria from tibolone or E2+MPA treated patients. Furthermore, only 9% of E2 regulated genes are also regulated by tibolone (85 out of 940), only 5% are also regulated by E2+MPA treatment and the overlap between tibolone and E2+MPA treatment is about 10%. This indicated that tibolone-treatment results in a weak endometrial profile similarity to E2 treatment and no profile similarity to E2+MPA treatment. A more detailed analysis showed that down stream processes, such as regulation of the cell cycle, angiogenesis and cell proliferation are almost not affected by tibolone treatment but, in contrast, are significantly affected by E2. For example, upon staining with Ki67, a marker for mitotic activity, significantly increased stromal as well as glandular cell proliferation was observed in the endometria from the E2-only treated group, while tibolone treatment resulted only in a slight increase in stromal cell proliferation (and no increase in glandular cell proliferation). These results indicate that in contrast to long-term tibolone use, short-term (21-days) use results in some estrogenic stimulation of the endometrium, which is clearly far less and rather different from what is observed during E2 treatment. References: Klaassens et al., 2006 Hanifi-Moghaddam et al., 2007 Verheul et al., 2007

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Dataset Information

Endogenous sex hormone changes in postmenopausal women in the diabetes prevention program.

Context

Objectives

Design

Participants

Interventions

Main outcome measures

Results

Conclusions

Publications

Endogenous sex hormone changes in postmenopausal women in the diabetes prevention program.

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