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Progesterone Amplifies Estrogen-stimulated Growth Hormone Secretion in Older Women

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02272647
Recruitment Status : Completed
First Posted : October 23, 2014
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
Johannes D. Veldhuis, Mayo Clinic

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: IM Saline Placebo (0.25 ml) Drug: IM Estradiol valerate (2.5 mg) Drug: IM Saline Placebo (0.5 ml) Drug: IM Estradiol valerate (5.0 mg) Drug: Oral Micronized Progesterone Drug: Oral Placebo Drug: Ghrelin (0.3 ug/kg) Drug: Medroxyprogesterone - Acetate Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Official Title: Progesterone Amplifies Estrogen-stimulated Growth Hormone Secretion in Older Women
Study Start Date : December 2014
Actual Primary Completion Date : December 2016
Actual Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hormones

Arm Intervention/treatment
Experimental: 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)
Drug: IM Saline Placebo (0.25 ml)
Drug: IM Saline Placebo (0.5 ml)
Drug: Oral Placebo
Drug: Ghrelin (0.3 ug/kg)
Drug: Oral Placebo
(in lieu of Medroxyprogesterone)

Experimental: 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)
Drug: IM Saline Placebo (0.25 ml)
Drug: IM Saline Placebo (0.5 ml)
Drug: Oral Micronized Progesterone
Drug: Ghrelin (0.3 ug/kg)
Drug: Oral Placebo
(in lieu of Medroxyprogesterone)

Experimental: 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)
Drug: IM Estradiol valerate (2.5 mg)
Drug: IM Estradiol valerate (5.0 mg)
Drug: Oral Placebo
Drug: Ghrelin (0.3 ug/kg)
Drug: Medroxyprogesterone - Acetate
Experimental: 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)
Drug: IM Estradiol valerate (2.5 mg)
Drug: IM Estradiol valerate (5.0 mg)
Drug: Oral Micronized Progesterone
Drug: Ghrelin (0.3 ug/kg)
Drug: Oral Placebo
(in lieu of Medroxyprogesterone)




Primary Outcome Measures :
  1. Logarithm of the ratio of the normalized growth hormone secretion rate over the first 10 hr. [ Time Frame: The subject will be followed on average for a month. Growth hormone measurements will occur on Day 23 after initiation of study drug administration ]
    Subjects will be given IM placebo/estradiol on Day 1. 10 days later they will receive IM placebo/estradiol again, then start progesterone/placebo capsules for 14 days. On Day 23, subjects will undergo a 12-h overnight (2200 - 1000h) fasting, 10-min blood sampling. The primary comparison parameter is the logarithm of the ratio of the normalized growth hormone secretion rate over the first 10 hr.


Secondary Outcome Measures :
  1. Growth hormone secretion post ghrelin injection [ Time Frame: The subject will be followed on average for a month. Growth hormone measurements will occur on Day 23 after initiation of study drug administration ]
    Subjects will be given IM placebo/estradiol on Day 1. 10 days later they will receive IM placebo/estradiol again, then start progesterone/placebo capsules for 14 days. On Day 23, subjects will undergo a 12-h overnight (2200 - 1000h) fasting, 10-min blood sampling. A secondary outcome is GH secretion over the 2 hr after bolus ghrelin injection, a potent growth hormone secretagogue



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02272647


Locations
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United States, Minnesota
Mayo Clinic in Rochester
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic

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Responsible Party: Johannes D. Veldhuis, Professor, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02272647    
Other Study ID Numbers: 14-002829
First Posted: October 23, 2014    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018
Keywords provided by Johannes D. Veldhuis, Mayo Clinic:
Normal Healthy Volunteers
Additional relevant MeSH terms:
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Medroxyprogesterone Acetate
Estradiol 3-benzoate
Estradiol 17 beta-cypionate
Medroxyprogesterone
Hormones
Estradiol
Polyestradiol phosphate
Progesterone
Estrogens
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Contraceptive Agents
Reproductive Control Agents
Contraceptive Agents, Female
Progestins
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Male
Antineoplastic Agents, Hormonal
Antineoplastic Agents