Micronized Estradiol and Progesterone: Effects on Carbohydrate Metabolism in Reproductive-Age Women

Thornton, Kim L.; DeFronzo, Ralph A.; Sherwin, Robert S.; Diamond, Michael P.

doi:10.1177/107155769500200411

Cited by 4 publications

(6 citation statements)

References 25 publications

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“…In contrast, premenopausal women taking oral doses of natural progesterone for 11-14 days exhibited no difference in HGP in the basal state or during a two-step hyperinsulinemic euglycemic clamp in studies carried out before and after treatment (65). HGP was similarly unaffected in women who took combined oral dosages of natural estradiol and progesterone (65). The route of progesterone administration (subcutaneous vs. oral), the progesterone levels achieved [>15 ng/ ml in the women vs. 95 ng/ml (equivalent to levels in the last trimester of pregnancy) in rats], or the duration of use may explain the differences in the human and rat findings.…”

Section: Discussionmentioning

confidence: 81%

“…During a low-dose hyperinsulinemic euglycemic clamp (circulating insulin ~2.5 times basal), the residual HGP in the progesterone-treated rats was 2.5 times greater than in the control animals, but in both groups HGP was virtually completely suppressed during high-dose insulin infusion (~20 times basal) (49). In contrast, premenopausal women taking oral doses of natural progesterone for 11-14 days exhibited no difference in HGP in the basal state or during a two-step hyperinsulinemic euglycemic clamp in studies carried out before and after treatment (65). HGP was similarly unaffected in women who took combined oral dosages of natural estradiol and progesterone (65).…”

Section: Discussionmentioning

confidence: 81%

“…This is likely because of the impact of simultaneous changes in the many other hormones and cytokines during pregnancy. In nonpregnant women and animal models, estradiol is commonly regarded as improving insulin sensitivity (39,51), but this is not observed in all investigations (62,65). Moreover, combining estradiol and progesterone treatment has been reported by some (51,63), but not all (39), investigators to reverse any estradiol-induced improvement in insulin sensitivity.…”

mentioning

confidence: 99%

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Chronic estradiol and progesterone treatment in conscious dogs: effects on insulin sensitivity and response to hypoglycemia

Batista¹,

Smith²,

Snead³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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We evaluated the effect of chronic (3 wk) subcutaneous treatment with progesterone and estradiol (PE; producing serum levels observed in the 3rd trimester of pregnancy) or placebo (C) on hepatic and whole body insulin sensitivity and response to hypoglycemia in conscious, overnight-fasted nonpregnant female dogs, using tracer and arteriovenous difference techniques. Insulin was infused peripherally for 3 h at 1.8 mU x kg(-1) x min(-1). Glucose was allowed to fall to 3 mM (Hypo) or maintained at 6 mM (Eugly) by peripheral glucose infusion. Insulin concentrations were significantly higher in Eugly-PE (n = 7) and Hypo-PE (n = 7) than in Eugly-C (n = 6) and Hypo-C groups (n = 7), but there were no significant differences in hepatic insulin extraction. Concentrations of glucagon, cortisol, epinephrine, and norepinephrine did not differ significantly between Eugly groups or between Hypo groups. Whole body glucose disposal, adjusted for the differences in insulin between groups, was 35% higher in Eugly-C vs. Eugly-PE groups (P < 0.05). Eugly-C and Eugly-PE groups exhibited similar rates of net hepatic glucose uptake, but the rate of glucose appearance was greater in Eugly-PE in the last hour (P < 0.05). Net hepatic glucose output was greater (P < 0.05) in Hypo-PE than in Hypo-C groups, and the glucose infusion rate required to maintain equivalent hypoglycemia was less (P < 0.05). The rate of gluconeogenic flux did not differ between Hypo groups. Chronic progesterone and estradiol exposure caused whole body (primarily skeletal muscle) insulin resistance and enhanced the liver's response to hypoglycemia without altering counterregulatory hormone concentrations.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 81%

mentioning

confidence: 99%

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Chronic estradiol and progesterone treatment in conscious dogs: effects on insulin sensitivity and response to hypoglycemia

Batista¹,

Smith²,

Snead³

et al. 2005

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Some studies have shown cycle-dependent differences in plasma insulin responses that were similar in magnitude to our study (38), albeit non-significant. Additionally, another study that attempted to experimentally reproduce luteal phase estradiol and progesterone levels by administration of oral micronized estradiol and progesterone found a similar magnitude increase in plasma insulin response to the hyperglycemic clamp (45). Importantly, we should stress that comparison of post-treatment insulin dynamics data to either baseline follicular or luteal phase measurements separately did not reveal an effect of GnRHa, suggesting that any cycle-dependent differences in insulin secretion would not impact the overall conclusions of our study.…”

Section: Discussionmentioning

confidence: 88%

“…Unfortunately, no study has directly measured the effect of ovarian hormones on glucose-induced glucose disposal. One study that attempted to experimentally reproduce luteal phase estradiol and progesterone levels by administration of oral micronized estradiol and progesterone failed to find an effect of either hormone alone or in combination on glucose disposal measured under euglycemic and hyperinsulinemic conditions (45), suggesting no effect of these hormones on glucose-induced glucose disposal. Thus, reasons to explain differences between the two studies are not readily apparent.…”

Section: Discussionmentioning

confidence: 99%

Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion

Toth¹,

Cooper

Pratley

et al. 2008

American Journal of Physiology-Endocrinology and Metabolism

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Several lines of evidence suggest that ovarian hormones influence glucose homeostasis, although their exact role in humans has not been clearly defined. In the present study, we sought to test the hypothesis that ovarian hormones regulate glucose homeostasis by examining the effect of pharmacologically-induced ovarian hormone deficiency on glucose disposal and insulin secretion. Young, healthy women with regular menstrual patterns were studied during the follicular and luteal phases of their cycle at baseline and after two months of treatment with gonadotropin-releasing hormone agonist (GnRHa; n=7) or placebo (n=6). Using hyperglycemic clamps, in combination with stable isotope-labeled (i.e., 13 C and 2 H) glucose tracers, we measured glucose disposal and insulin secretion. Additionally, we assessed body composition and regional fat distribution using radiologic imaging techniques, as well as glucoregulatory hormones. Ovarian hormone suppression with GnRHa did not alter body composition, abdominal fat distribution or thigh tissue composition. There was no effect of ovarian suppression on total, oxidative or non-oxidative glucose disposal expressed relative to plasma insulin level. Similarly, no effect of ovarian hormone deficiency was observed on first-or second phase insulin secretion or insulin clearance. Finally, ovarian hormone deficiency was associated with an increase in circulating adiponectin levels, but no change in leptin concentration. Our findings suggest that a brief period of ovarian hormone deficiency in young, healthy eugonadal women does not alter glucose disposal index or insulin secretion, supporting the conclusion that ovarian hormones play a minimal role in regulating glucose homeostasis. Our data do, however, support a role for ovarian hormones in the regulation of plasma adiponectin levels.

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Plasma Insulin and Glucagon Concentrations and Biochemical Variables in Regularly Menstruating Females with Ovulatory and Anovulatory Menstrual Cycles

2003

Horm Metab Res

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Ovarian hormones are known to affect endocrine pancreas function. However, data concerning the effects of anovulatory menstrual cycles in regularly menstruating women on endocrine pancreas and blood metabolites are lacking. We examined plasma insulin, glucagon, glucose, lactate, urea and glycerol concentrations in reproductive-age, regularly menstruating females classified as ovulating or non-ovulating on the basis of basal body temperature measurements and plasma 17beta-estradiol and progesterone determinations. All measurements were performed twice--in the follicular and again in the luteal phases of the menstrual cycle. There were no differences in plasma lactate and glycerol concentrations between the two groups of subjects. Plasma insulin concentrations tended to be lower in non-ovulating than in ovulating women. In addition, plasma glucagon did not differ in the follicular (33.2 pmol/l) or luteal phase of the menstrual cycle in females with disturbed ovarian hormone secretion (34.1 pmol/l). In contrast, plasma glucagon concentrations in the luteal phase (32.8 pmol/l) were significantly higher than in the follicular phase (24.9 pmol/l) of the menstrual cycle in ovulating women. Plasma glucose concentrations in the follicular phase of the menstrual cycle in non-ovulating women (4.1 mmol/l) were slightly but significantly lower than in their ovulating counterparts (5.3 mmol/l). Furthermore, no correlations were noted between plasma glucose and insulin-to-glucagon molar ratio in non-ovulating subjects. Plasma urea concentrations in non-ovulating women were markedly lower than in ovulating women in both follicular and luteal phases of the menstrual cycle (4.1 and 3.9 mmol/l vs. 5.3 and 5.4 mmol/l in non-ovulating and ovulating women, respectively). In ovulating women, plasma urea levels in both cycle phases were significantly correlated with plasma glucagon concentrations, but no such correlation was found in non-ovulating women. In conclusion, anovulatory menstrual cycles in premenopausal females slightly altered pancreatic hormone plasma levels but markedly impaired their action on plasma glucose and urea concentrations.

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Micronized Estradiol and Progesterone: Effects on Carbohydrate Metabolism in Reproductive-Age Women

Cited by 4 publications

References 25 publications

Chronic estradiol and progesterone treatment in conscious dogs: effects on insulin sensitivity and response to hypoglycemia

Chronic estradiol and progesterone treatment in conscious dogs: effects on insulin sensitivity and response to hypoglycemia

Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion

Plasma Insulin and Glucagon Concentrations and Biochemical Variables in Regularly Menstruating Females with Ovulatory and Anovulatory Menstrual Cycles

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