Shengchun Kong

Racial/Ethnic Differences in Sex Hormone Levels among Postmenopausal Women in the Diabetes Prevention Program

CONTEXT Sex hormones may differ by race/ethnicity in postmenopausal women. Whether racial/ethnic differences also exist among those who are overweight and glucose intolerant is not clear. OBJECTIVES The objective of the study was to compare sex hormones by race/ethnicity [non-Hispanic white (NHW), Hispanic, African-American (AA)] in overweight, glucose-intolerant, postmenopausal women. DESIGN This was a secondary analysis of a randomized controlled trial. PARTICIPANTS Participants included postmenopausal glucose-intolerant women participating in the Diabetes Prevention Program. INTERVENTIONS Interventions included intensive lifestyle modification (consisting of diet and physical activity) or metformin 850 mg twice a day vs. placebo. MAIN OUTCOME MEASURES Baseline levels and 1-yr intervention-related changes in SHBG, total and bioavailable estradiol (E2), total and bioavailable testosterone, and dehydroepiandrosterone were measured. RESULTS At baseline, among women not using estrogen (n = 370), NHW had higher total and bioavailable E2 and testosterone levels than Hispanics independent of age, type of menopause, waist circumference, alcohol intake, and current smoking. NHW also had higher levels of bioavailable E2 and lower levels of SHBG than AA. At baseline, among estrogen users (n = 310), NHW had higher total and bioavailable E2 than Hispanics and higher levels of SHBG than AA after adjustment. At 1 yr, among women not using estrogen, NHW had larger declines in total E2 and bioavailable E2 levels than AA after adjustment for the above covariates, changes in waist circumference, and randomization arm. At 1 yr, among estrogen users, sex hormone changes did not differ by race/ethnicity. CONCLUSIONS Among postmenopausal women, there were significant race/ethnicity differences in baseline sex hormones and changes in sex hormones.

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

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.

Changes in Iron Measures over Menopause and Associations with Insulin Resistance

OBJECTIVES No longitudinal studies have examined how iron measures change over menopause. Our objectives were to examine iron measures in individual women at premenopause and at postmenopause and, secondarily, to determine if any changes contributed to insulin resistance. METHODS In a subset of participants (n=70) in a longitudinal study of menopause, we measured ferritin, transferrin, and soluble transferrin receptor (sTfR) once in the premenopause and once in the postmenopause. We also examined associations between menopausal status and change in iron markers after adjustment for age at menopause, race/ethnicity, and waist circumference. In linear regression models, we examined associations between premenopause iron measures and changes in iron markers over menopause with homeostasis model assessment of insulin resistance (HOMA-IR) changes over menopause, before and after adjustment for age at menopause, race/ethnicity, changes in waist circumference, C-reactive protein (CRP), and sex hormone-binding globulin (SHBG) levels. RESULTS Women had lower ferritin (p<0.01), higher sTfR:ferritin levels (p<0.01), lower HOMA-IR (p=0.022), and lower glucose (p=0.05) in premenopause compared to postmenopause. After adjustment, lower premenopausal iron levels (sTfR:ferritin levels β=11.0, 95% confidence interval [CI] 0.017-22.0) and larger increases in iron over menopause (changes in sTfR:ferritin β=13.6, 95% CI 0.93-26.3) were associated with larger increases in HOMA-IR. CONCLUSIONS From premenopause to postmenopause, women on average have increases in measures of iron stores. Women who had the greatest changes in iron over menopause (lower measures of premenopausal iron and greater increases in iron measures over the menopause) had the strongest associations between changes in iron and changes in insulin resistance.

Reductions in glucose among postmenopausal women who use and do not use estrogen therapy

ObjectiveAmong postmenopausal women who do not use estrogen therapy (ET), we have previously reported that intensive lifestyle modification (ILS) leads to increases in sex hormone–binding globulin (SHBG) and that such increases are associated with reductions in fasting plasma glucose (FPG) and 2-hour postchallenge glucose (2HG). Oral ET decreases FPG and increases 2HG while increasing both SHBG and estradiol (E2). It is unknown if ILS reduces glucose among ET users, if changes in SHBG and E2 might mediate any glucose decreases in ET users, and if these patterns differ from those in non-ET users. MethodsWe conducted a secondary analysis of postmenopausal women in the Diabetes Prevention Program who used ET at baseline and 1-year follow-up (n = 324) and who did not use ET at either time point (n = 382). Participants were randomized to ILS, metformin, or placebo administered at 850 mg BID. ResultsET users were younger, more often white, and more likely to have had bilateral oophorectomy than non-ET users. Among ET users, ILS reduced FPG (P < 0.01) and 2HG (P < 0.01), and metformin reduced FPG (P < 0.01) but not 2HG (P = 0.56), compared with placebo. Associations between SHBG and total E2 with FPG and 2HG were not significant among women randomized to ILS or metformin. These patterns differed from those observed among women who did not use ET. ConclusionsWe conclude that among glucose-intolerant ET users, interventions to reduce glucose are effective but possibly mediated through different pathways than among women who do not use ET.

Racial/ethnic differences in hepatic steatosis in a population-based cohort of post-menopausal women: The Michigan Study of Women's Health Across the Nation

The prevalence of hepatic steatosis may differ between post‐menopausal African‐American women and non‐Hispanic white women and by sex hormone binding globulin level. We examined prevalence of hepatic steatosis by race/ethnicity and associations with sex hormone binding globulin.

Conditional Modeling of Longitudinal Data With Terminal Event

ABSTRACT We consider a random effects model for longitudinal data with the occurrence of an informative terminal event that is subject to right censoring. Existing methods for analyzing such data include the joint modeling approach using latent frailty and the marginal estimating equation approach using inverse probability weighting; in both cases the effect of the terminal event on the response variable is not explicit and thus not easily interpreted. In contrast, we treat the terminal event time as a covariate in a conditional model for the longitudinal data, which provides a straightforward interpretation while keeping the usual relationship of interest between the longitudinally measured response variable and covariates for times that are far from the terminal event. A two-stage semiparametric likelihood-based approach is proposed for estimating the regression parameters; first, the conditional distribution of the right-censored terminal event time given other covariates is estimated and then the likelihood function for the longitudinal event given the terminal event and other regression parameters is maximized. The method is illustrated by numerical simulations and by analyzing medical cost data for patients with end-stage renal disease. Desirable asymptotic properties are provided. Supplementary materials for this article are available online.

Sex Hormone Binding Globulin and Sex Steroids Among Premenopausal Women in the Diabetes Prevention Program

CONTEXT It is unknown whether intensive lifestyle modification (ILS) or metformin changes sex steroids among premenopausal women without a history of polycystic ovarian syndrome (PCOS). OBJECTIVES We examined 1-year intervention impact on sex steroids (estradiol, testosterone, dehydroepiandrosterone, and androstenedione [A4]) and SHBG and differences by race/ethnicity. PARTICIPANTS A subgroup of Diabetes Prevention Program participants who were premenopausal, not using estrogen, without a history of PCOS or irregular menses, and who reported non-Hispanic white (NHW), Hispanic, or African-American race/ethnicity (n = 301). INTERVENTIONS Randomization arms were 1) ILS with the goals of weight reduction of 7% of initial weight and 150 minutes per week of moderate intensity exercise, 2) metformin 850 mg twice a day, or 3) placebo. RESULTS Neither intervention changed sex steroids compared to placebo. ILS, but not metformin, increased median SHBG by 3.1 nmol/L (~11%) compared to decreases of 1.1 nmol/L in the placebo arm (P < .05). This comparison remained significant after adjustment for changes in covariates including waist circumference. However, associations with glucose were not significant. Median baseline A4 was lower in Hispanics compared to NHWs (5.7 nmol/L vs 6.5 nmol/L, P < .05) and increases in A4 were greater in Hispanics compared to NHWs (3.0 nmol/ vs 1.2 nmol/L, P < .05), and these differences did not differ significantly by intervention arm. No other racial/ethnic differences were significant. CONCLUSIONS Among premenopausal glucose-intolerant women, no intervention changed sex steroids. ILS increased SHBG, although associations with glucose were not significant. SHBG and sex steroids were similar by race/ethnicity, with the possible exception of lower baseline A4 levels in Hispanics compared to NHWs.

The association of elective hormone therapy with changes in lipids among glucose intolerant postmenopausal women in the diabetes prevention program

OBJECTIVE It is unclear how lipids change in response to lifestyle modification or metformin among postmenopausal glucose intolerant women using and not using hormone therapy (HT). We examined the one-year changes in lipids among postmenopausal, prediabetic women in the Diabetes Prevention Program (DPP), and whether changes were mediated by sex hormones. MATERIALS/METHODS We performed a secondary analysis of a randomized controlled trial of 342 women who used HT at baseline and year 1 and 382 women who did not use HT at either time point. Interventions included intensive lifestyle (ILS) with goals of weight reduction of at least 7% of initial weight and 150 minutes per week of moderate intensity exercise, or metformin or placebo administered 850 mg up to twice a day. Women were not randomized to HT. Main outcome measures were changes between baseline and study year 1 in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. RESULTS Compared to placebo, both ILS and metformin significantly reduced LDL-C and raised HDL-C among HT users, changes partially explained by change in estradiol and testosterone but independent of changes in waist circumference and 1/fasting insulin. In contrast, DPP interventions had no effect on LDL-C and HDL-C among non-HT users. ILS significantly lowered triglycerides among non-users but did not significantly change triglycerides among HT users. Metformin did not significantly change triglycerides among non-users but increased triglycerides among HT users. CONCLUSIONS The beneficial effects of ILS and metformin on lowering LDL-C and raising HDL-C differ depending upon concurrent HT use.

Does hormone therapy affect blood pressure changes in the Diabetes Prevention Program

ObjectiveThis study aims to examine whether blood pressure reductions differ by estrogen use among overweight glucose-intolerant women. MethodsWe conducted a secondary analysis of Diabetes Prevention Program postmenopausal participants who used oral estrogen with or without progestogen at baseline and 1-year follow-up (n = 324) versus those who did not use oral estrogen with or without progestogen at either time point (n = 382). Changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were examined by randomization arm (intensive lifestyle change [ILS], metformin 850 mg twice daily, or placebo). Associations between changes in blood pressure and changes in sex hormone–binding globulin, estradiol, testosterone, and dehydroepiandrosterone were also examined. ResultsEstrogen users and nonusers had similar prevalences of baseline hypertension (33% vs 34%, P = 0.82) and use of blood pressure medications at baseline (P = 0.25) and on follow-up (P = 0.10). Estrogen users and nonusers randomized to ILS had similar decreases in SBP (−3.3 vs −4.7 mm Hg, P = 0.45) and DBP (−3.1 vs −4.7 mm Hg, P = 0.16). Among estrogen users, women randomized to ILS had significant declines in SBP (P = 0.016) and DBP (P = 0.009) versus placebo. Among nonusers, women randomized to ILS had significant declines in DBP (P = 0.001) versus placebo, but declines in SBP were not significant (P = 0.11). Metformin was not associated with blood pressure reductions versus placebo regardless of estrogen therapy. Blood pressure changes were not associated with changes in sex hormones regardless of estrogen therapy. ConclusionsAmong overweight women with dysglycemia, the magnitude of blood pressure reductions after ILS is unrelated to postmenopausal estrogen use.

Sex steroid levels and response to weight loss interventions among postmenopausal women in the Diabetes Prevention Program

To examine whether estrogen use potentiates weight loss interventions via sex steroid levels and whether endogenous sex steroid levels predict response to weight loss interventions among women not using estrogen.