Dataset Information

Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type determine pulsatile growth hormone secretion in healthy women: studies using submaximal agonist drive and an estrogen clamp.

ABSTRACT:

Context

GH-releasing peptide (GHRP), GHRH, and somatostatin are physiological regulators of pulsatile GH secretion.

Hypothesis

Age, independently of abdominal visceral fat (AVF) and basal (nonpulsatile) GH secretion, damps pulsatile GH secretion driven by physiological (rather than pharmacological) amounts of GHRP and GHRH in an experimentally controlled estradiol (E(2)) milieu.

Design and setting

A prospectively randomized, double-blind parallel-cohort study was conducted at an academic medical center.

Participants

Community-dwelling healthy premenopausal (PRE, age 24 +/- 0.8 yr, n = 20) and postmenopausal (POST, age 63 +/- 1.8 yr, n = 22) women participated in the study.

Interventions

Gonadal-axis down-regulation with leuprolide was followed by randomized addback of placebo or transdermal E(2) and separate-day iv bolus injections of a half-maximally stimulatory dose of GHRP-2 or GHRH (each 0.33 mug/kg).

Analysis

Three-way analysis of covariance included main factors age, E(2) status, and secretagogue type and covariates AVF and basal GH secretion.

Results

Submaximally stimulated pulsatile GH secretion was positively determined by PRE vs. POST age (P < 0.001), E(2) repletion vs. depletion (P = 0.001) and GHRP-2 vs. GHRH stimulation (P < 0.001), after adjustment for AVF and basal secretion. E(2) vs. placebo elevated fasting mean GH concentrations in both PRE and POST women (P = 0.006) but increased basal (nonpulsatile) GH secretion in PRE only (P = 0.002). PRE vs. POST age prolonged GHRH-driven GH secretory bursts by 36% (P = 0.006).

Conclusion

PRE vs. POST age, E(2) availability, and physiological peptide drive are triple determinants of pulsatile GH secretion independently of abdominal visceral fat and nonpulsatile GH secretion in healthy women.

SUBMITTER: Hudson SB

PROVIDER: S-EPMC2805499 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Publications

Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type determine pulsatile growth hormone secretion in healthy women: studies using submaximal agonist drive and an estrogen clamp.

Hudson Susan B SB Schroeder Darrell R DR Bailey Joy N JN Mielke Kristi L KL Erickson Dana D Miles John M JM Bowers Cyril Y CY Veldhuis Johannes D JD

The Journal of clinical endocrinology and metabolism 20091026 1

<h4>Context</h4>GH-releasing peptide (GHRP), GHRH, and somatostatin are physiological regulators of pulsatile GH secretion.<h4>Hypothesis</h4>Age, independently of abdominal visceral fat (AVF) and basal (nonpulsatile) GH secretion, damps pulsatile GH secretion driven by physiological (rather than pharmacological) amounts of GHRP and GHRH in an experimentally controlled estradiol (E(2)) milieu.<h4>Design and setting</h4>A prospectively randomized, double-blind parallel-cohort study was conducted ...[more]

PMID: 19858315

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Project description:ImportanceHalf of women who are postmenopausal have genitourinary discomfort after menopause. Recommended therapies include low-dose vaginal estrogen. Individuals with a history of breast cancer or venous thromboembolism may have concerns about the safety of this intervention.ObjectiveTo compare serum estrogen concentrations with the use of vaginal estrogen, 10 μg, tablet vs placebo in women who are postmenopausal.Design, setting, and participantsThis is a secondary, post hoc analysis of data from a randomized clinical trial of treatment for moderate to severe genitourinary syndrome in women who are postmenopausal. The study was conducted at Kaiser Permanente Washington Health Research Institute and the University of Minnesota from April 11, 2016, to April 23, 2017. Measurements and data analysis were performed from November 3, 2020, to September 23, 2022.InterventionsParticipants were randomly assigned to vaginal estradiol tablet (10 μg/d for 2 weeks and then twice weekly) plus placebo gel (3 times weekly) or dual placebo for 12 weeks.Main outcomes and measuresIn this post hoc analysis, baseline and week 12 serum estradiol, estrone, and sex hormone-binding globulin (SHBG) concentrations were measured by a chemiluminescent assay. Week 12 values of the 3 analytes were compared by baseline participant characteristics. Linear models compared week 12 estradiol concentrations between treatment groups, adjusted for baseline characteristics.ResultsA total of 174 women, mean (SD) age 61 (4) years, were included. Those in the estrogen group (n = 88) were more likely to have higher geometric mean (SD) week 12 serum estradiol concentrations (4.3 [2.2 pg/mL]) than those in the placebo group (n = 86) (3.5 [2.1] pg/mL) (P = .01). Adjusted for pretreatment hormone concentrations, age, clinical site, and body mass index, assignment to the estrogen vs placebo treatment group was significantly associated with higher week 12 estradiol concentrations (23.8% difference; 95% CI, 6.9%-43.3%). Most (121 of 174 [69.5%]) participants had enrollment serum estradiol concentrations higher than 2.7 pg/mL. Of women starting treatment at estradiol levels lower than or equal to 2.7 pg/mL, 38.1% (8 of 21) in the estrogen group and 34.4% (11 of 32) in the placebo group had estradiol concentrations higher than 2.7 pg/mL after 12 weeks of study participation (P = .78). Treatment assignment was not associated with week 12 estrone or SHBG concentrations.Conclusions and relevanceIn this secondary analysis of a randomized clinical trial, a significant, although small, increase in serum estradiol levels was noted after 12 weeks of vaginal estrogen administration. The clinical relevance of this small increase is uncertain.Trial registrationClinicalTrials.gov Identifier: NCT02516202.

Dataset Information

Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type determine pulsatile growth hormone secretion in healthy women: studies using submaximal agonist drive and an estrogen clamp.

Context

Hypothesis

Design and setting

Participants

Interventions

Analysis

Results

Conclusion

Publications

Pre- versus postmenopausal age, estradiol, and peptide-secretagogue type determine pulsatile growth hormone secretion in healthy women: studies using submaximal agonist drive and an estrogen clamp.

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