Progesterone Amplifies Estrogen-stimulated Growth Hormone Secretion in Older Women

NCT ID: NCT02272647

Last Updated: 2018-03-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2018-02-28

Brief Summary

Progesterone amplifies estrogen-stimulated Growth Hormone (GH) secretion in postmenopausal women. Preliminary data are sought to estimate statistical power for more detailed studies of this hypothesis.

Detailed Description

The systemic availability and orderly secretion patterns of GH and sex steroids decline in healthy aging men and women. The combined changes have substantial clinical implications to aging-related physical frailty, diminished aerobic capacity, sarcopenia, osteopenia, visceral adiposity, glucose intolerance, and reduced psychosocial wellbeing. Whereas androgen is considered the main trophic (anabolic) sex steroid, recent data demonstrate that certain tissues respond principally to GH and testosterone-derived estradiol, Estrogen (E2) (e.g. bone, brain, liver and pituitary). In principle, frailty may thus be associated with dual GH and sex-steroid deficiencies. Additionally, young, but not older healthy women secrete significant amounts of progesterone for approximately 14 days during the luteal phase of every menstrual cycle. When GH levels rise nearly two fold, the investigators hypothesize that progesterone potentiates the GH response to E2. This hypothesis arises from scattered indirect studies often using synthetic progestins with partial androgen agonism, instead of progesterone per se.

Because there is no basis for estimating statistical power for this novel paradigm, 40 women, 10 each in 4 groups, will be studied. The pilot data will be used to calculate statistical power for a definitive R01-based investigation of gender-specific distinctions in estrogen-regulated pituitary-hormone secretion.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

IM Plac - Oral Plac - Ghrelin

Day 1: IM Saline Placebo (0.25 ml) Day 10: IM Saline Placebo (0.5 ml) and Oral Placebo 3x/day Day 23: IV push of ghrelin (0.3 ug/kg) + Placebo (for 10 days)

Group Type: EXPERIMENTAL

IM Saline Placebo (0.25 ml)

Intervention Type: DRUG

IM Saline Placebo (0.5 ml)

Intervention Type: DRUG

Oral Placebo

Intervention Type: DRUG

Ghrelin (0.3 ug/kg)

Intervention Type: DRUG

Oral Placebo

Intervention Type: DRUG

(in lieu of Medroxyprogesterone)

IM Plac - Oral Prog - Ghrelin

Day 1: IM Saline Placebo (0.25 ml) Day 10: IM Saline Placebo (0.5 ml) and Oral Micronized Progesterone 3x/day Day 23: IV push of ghrelin (0.3 ug/kg) + Placebo (for 10 days)

Group Type: EXPERIMENTAL

IM Saline Placebo (0.25 ml)

Intervention Type: DRUG

IM Saline Placebo (0.5 ml)

Intervention Type: DRUG

Oral Micronized Progesterone

Intervention Type: DRUG

Ghrelin (0.3 ug/kg)

Intervention Type: DRUG

Oral Placebo

Intervention Type: DRUG

(in lieu of Medroxyprogesterone)

IM E2 - Oral Plac - Ghrelin

Day 1: IM Estradiol (2.5 mg) Day 10: IM Estradiol (5.0 mg) and Oral Placebo 3x/day Day 23: IV push of ghrelin (0.3 ug/kg) + Medroxyprogesterone (5 mg - for 10 days)

Group Type: EXPERIMENTAL

IM Estradiol valerate (2.5 mg)

Intervention Type: DRUG

IM Estradiol valerate (5.0 mg)

Intervention Type: DRUG

Oral Placebo

Intervention Type: DRUG

Ghrelin (0.3 ug/kg)

Intervention Type: DRUG

Medroxyprogesterone - Acetate

Intervention Type: DRUG

IM E2 - Oral Prog - Ghrelin

Day 1: IM Estradiol (2.5 mg) Day 10: IM Estradiol (5.0 mg) and Oral Micronized Progesterone 3x/day Day 23: IV push of ghrelin (0.3 ug/kg) + Placebo (for 10 days)

Group Type: EXPERIMENTAL

IM Estradiol valerate (2.5 mg)

Intervention Type: DRUG

IM Estradiol valerate (5.0 mg)

Intervention Type: DRUG

Oral Micronized Progesterone

Intervention Type: DRUG

Ghrelin (0.3 ug/kg)

Intervention Type: DRUG

Oral Placebo

Intervention Type: DRUG

(in lieu of Medroxyprogesterone)

Interventions

IM Saline Placebo (0.25 ml)

Intervention Type: DRUG

IM Estradiol valerate (2.5 mg)

Intervention Type: DRUG

IM Saline Placebo (0.5 ml)

Intervention Type: DRUG

IM Estradiol valerate (5.0 mg)

Intervention Type: DRUG

Oral Micronized Progesterone

Intervention Type: DRUG

Oral Placebo

Intervention Type: DRUG

Ghrelin (0.3 ug/kg)

Intervention Type: DRUG

Medroxyprogesterone - Acetate

Intervention Type: DRUG

Oral Placebo

(in lieu of Medroxyprogesterone)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• women ages 50 to 80
• postmenopausal as defined by: any combination of the following

• Hormonally postmenopausal for 1 year
• Lh greater than 15 IU/L, FSH greater than 30 IU/L
• Total hysterectomy with oophorectomy greater than one year
• Hysterectomy with ovaries preserved with hormone levels: Lh > 15 IU/L, FSH > 30 IU/L
• Following laboratory results with normal range, unless PI approves out of range values.
• BMI 18 to 35

Exclusion Criteria

• structural hypothalamo-pituitary-gonadal disease
• endocrinopathy (diseases involving the following organs pituitary, thyroid, adrenals, ovaries, testes and pancreas), other than primary thyroid failure receiving replacement
• recent (within 2 weeks) estrogen, progestin, anabolic steroid or glucocorticoid use
• clinically significant ECG abnormality as determined by study team physicians
• obstructive uropathy
• history of a stroke
• history of MI or angina
• acute or chronic systemic disease
• recent transmeridian travel (traversing more than 3 time zones within 7 days of admission)
• current night shift work
• concurrent use of neuropsychiatric medications
• alcohol or drug abuse, current and within 2 years
• history of depression, psychosis, or mania
• weight gain or loss (2 kg or more in 3 weeks)
• BMI > 35 kg/m2
• anemia, hemoglobin less than 12.5 g/dl
• abnormal hepatorenal function, creatinine outside normal range, ALT greater than two times normal range
• biochemical and chemistry lab results out of physician acceptable range
• history of deep-vein thrombophlebitis
• history of Congestive Heart Failure, cardiac arrhythmias, and medications used to treat cardiac arrhythmias
• known allergy to estradiol valerate, castor oil or sesame oil
• history of smoking within the last 2 years
• untreated gall bladder disease
• lack of voluntary, written informed consent
• history of carcinoma excluding localized basal cell or squamous cell, including women with known, suspected or history of breast cancer
• not clinically postmenopausal
• women with allergies to nuts will not be enrolled in the study.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Johannes D. Veldhuis

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Countries

United States

Other Identifiers

14-002829

Identifier Type: -

Identifier Source: org_study_id