Impact of Estradiol Addback

Phase 1

Completed

• Conditions: Normal Healthy Volunteers
• Interventions: Drug: Degarelix; Drug: Testosterone; Drug: Anastrozole; Drug: Estrogen patch

• Registration Number: NCT01862835
• Lead Sponsor: Mayo Clinic

Brief Summary

Repletion of testosterone (T) in older men drives Growth Hormone secretion after its aromatization to estradiol (E2) by potentiating endogenous GH drive.

Detailed Description

Systemic concentrations of Te, E2, GH, Insulin-like Growth Factor-I and IGFBP-3 decline in healthy aging men. Relative sex-steroid deprivation accentuates GH and IGF-I depletion, since Te stimulates GH and IGF-I production in older men, hypogonadal males of all ages, and patients undergoing (genotypic female-to-male) gender reassignment. Tamoxifen blocks this effect of Te, suggesting involvement of E2 in GH's stimulation in men. E2 per se stimulates GH secretion in women. Because Te is converted to E2 by aromatization in the body, we postulate that E2 is the active moiety in men also. Moreover, we hypothesize that the decline of E2 in older men contributes to the fall in GH output. This has never been tested. From a clinical vantage, understanding the mechanistic basis of Te's drive of the somatotropic axis is especially relevant in boys with pubertal failure, adults with primary hypogonadism and men with aging-related hypoandrogenemia. In relation to aging in the male, testosterone and E2 bioavailabilities fall by 35-50% in the eighth compared with third decade of life. From a medical perspective, aging is accompanied by progressive osteopenia, sarcopenia and intra-abdominal obesity. These adverse outcomes are remediable by short-term replacement with Te and/or recombinant GH, thus linking GH/Te/E2 availability with key body-compositional features.

Study Timeline

• Study Start: 2013-05
• Study First Submitted: 2013-05-22
• Study First Submitted QC: 2013-05-22
• Study First Posted: 2013-05-27
• Primary Completion: 2016-09-30
• Study Completion: 2018-12-30
• Status Verified: 2019-06
• Last Update Submitted: 2019-06-05
• Last Update Posted: 2019-06-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 43

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
degarelix/Te/anastrozole/ placebo	Degarelix	degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
degarelix/Te/anastrozole/ placebo	Anastrozole	degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
degarelix/Te/ anastrozole/E2 patch	Estrogen patch	degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
Degarelix/Te/placebo/ placebo	Degarelix	Degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral placebo once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
Degarelix/Te/placebo/ placebo	Testosterone	Degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral placebo once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
degarelix/Te/anastrozole/ placebo	Testosterone	degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.
degarelix/Te/ anastrozole/E2 patch	Degarelix	degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
degarelix/Te/ anastrozole/E2 patch	Testosterone	degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
degarelix/Te/ anastrozole/E2 patch	Anastrozole	degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; Te enanthate 100 mg i.m. given on day 1, 8 and 15; Oral anastrozole 2.0 mg once daily x 22 days; and an E2 patch calibrated to deliver 0.05 mg/day E2 beginning on day 1 and changed every 3 days through day 22.
degarelix/ placebo/placebo/no patch	Degarelix	degarelix 80 mg (given as two s.c. injections of 60 mg) once \[called day 1\]; placebo i.m. given on day 1, 8 and 15; Oral placebo once daily x 22 days; and no patch beginning on day 1 and changed every 3 days through day 22.

Primary Outcome Measures

Name	Time	Method
BioStatistical Analysis	Subjects will undergo 15-h overnight (2200 - 1300 h) fasting, 10-min blood sampling	The primary analytical outcome is the summed mass of GH secreted in pulses over the 15 h of overnight blood sampling. The outcome measure is relevant, since sex-steroid hormones and regulatory peptides uniquely control GH secretory-burst mass.

Trial Locations

Locations (1)

Mayo Clinic in Rochester; 🇺🇸 Rochester, Minnesota, United States