Study of the Effect of Testosterone and Estradiol on NP Responses to Acute and Chronic Salt Loading
- Registration Number
- NCT01763541
- Lead Sponsor
- Massachusetts General Hospital
- Brief Summary
There is gender dimorphism in cardiovascular risk, with men at higher risk than women. However, the fundamental basis for the protective effect of female sex remains unclear. Recent data implicate the natriuretic peptide (NP) system as an important determinant of blood pressure. Also, NP levels are twice as high in women of reproductive age than in men, and gonadal steroids are important determinants of circulating NPs. These are the marked, but poorly understood differences in the NP status between men and women. The investigators hypothesize that gonadal steroids regulate NP release, specifically that testosterone inhibits and estrogen activates the NP axis, leading to differences in both resting NP levels and dynamic responses of the NP, RAAS, and kidneys to acute and chronic salt loading. Understanding the basis for gender differences in NP function should provide important insights regarding mechanisms underlying hypertension in men versus women.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- 18-40 years old
- no history of hypertension
- normal BMI
- Male: normal testosterone and free testosterone levels
- Female: regular menses, negative pregnancy test, no sex steroid therapy >/=3 mos
- on hypertensives, diuretics, or insulin
- with diabetes mellitus
- estimated creatinine clearance <60 ml/min
- prior cardiovascular, liver or renal disease
- history of hormonally-responsive cancer
- elevated liver function test (LFTs)
- atrial fibrillation
- abnormal sodium or potassium levels
- taking medications that directly impact the endocrine system (exogenous hormones, steroids, etc.)
- taking medications that indirectly impact the endocrine system (SSRIs, opioids, finasteride, etc.)
- with untreated hyper- or hypothyroidism
- smoker
- psychiatric history
- Women: not willing to abstain from getting pregnant during the course of the study, with abnormal menstrual cycle, or who have osteoporosis
- Men: with polycythemia
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Testosterone leuprolide acetate To determine the effect of testosterone on the NP responses to acute and chronic salt loading. One testosterone patch (Androderm 5 mg) applied to each male subject each day for 14 days. Intervention: Leuprolide acetate and anastrozole Testosterone Anastrozole To determine the effect of testosterone on the NP responses to acute and chronic salt loading. One testosterone patch (Androderm 5 mg) applied to each male subject each day for 14 days. Intervention: Leuprolide acetate and anastrozole Estradiol leuprolide acetate To determine the effect of estradiol on the NP responses to acute and chronic salt loading. Two estradiol patches (Vivelle Dot 0.1mg) will be applied to each female subject twice-a-week for 2 weeks. Intervention: leuprolide acetate
- Primary Outcome Measures
Name Time Method NP levels in men with testosterone patch and low-salt diet At day 7 of week of testosterone administration with low-salt diet B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in men with testosterone patch and high-salt diet At day 7 of week of testosterone administration with high-salt diet B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in women with estradiol patch and low-salt diet At day 7 of week of estradiol administration with low-salt diet B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in women with estradiol patch and high-salt diet At day 7 of week of estradiol administration with high-salt diet B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in men with placebo patch and low-salt diet At day 7 of week of placebo administration with low-salt diet B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in men with placebo patch and high-salt diet At day 7 of week of placebo administration with high-salt diet B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in women with placebo patch and low-salt diet At day 7 of week of placebo administration with low-salt diet B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
NP levels in women with placebo patch and high-salt diet At day 7 of week of placebo administration with high-salt diet B-type natriuretic peptide (BNP), Atrial natriuretic peptide (ANP), amino-terminal brain natiuretic peptide (N-BNP), amino-terminal atrial natiuretic peptide (N-ANP), cyclic guanosine monophosphate (cGMP)
- Secondary Outcome Measures
Name Time Method Plasma Renin Activity (PRA) levels in women on estradiol on low-salt diet At day 7 of week of estradiol administration on low-salt diet Plasma Renin Activity (PRA)
Aldosterone levels in men with testosterone on low-salt diet At day 7 of week of testosterone administration on low-salt diet Aldosterone
Plasma Renin Activity (PRA) levels in women on estradiol on high-salt diet At days 6 and 7 of week of estradiol administration on high-salt diet Plasma Renin Activity (PRA)
Plasma Renin Activity (PRA) levels in women on placebo on low-salt diet At day 7 of week of placebo administration on low-salt diet Plasma Renin Activity (PRA)
Plasma Renin Activity (PRA) levels in women on placebo on high-salt diet At days 6 and 7 of week of placebo administration on high-salt diet Plasma Renin Activity (PRA)
Plasma Renin Activity (PRA) levels in men on testosterone on low-salt diet At day 7 of week of testosterone administration on low-salt diet Plasma Renin Activity (PRA) levels in men on testosterone on high-salt diet At days 6 and 7 of week of testosterone administration on high-salt diet Plasma Renin Activity (PRA) levels in men on placebo on low-salt diet At day 7 of week of placebo administration on low-salt diet Plasma Renin Activity (PRA) levels in men on placebo on high-salt diet At days 6 and 7 of week of placebo administration on high-salt diet Aldosterone levels in men on testosterone on high-salt diet At days 6 and 7 of week of testosterone administration on high-salt diet Aldosterone levels in men on placebo on high-salt diet At days 6 and 7 of week of placebo administration on high-salt diet Aldosterone levels in men on placebo on low-salt diet At day 7 of week of placebo administration on low-salt diet Aldosterone levels in women on estradiol on high-salt diet At days 6 and 7 of week of estradiol administration on high-salt diet Aldosterone levels in women on estradiol on low-salt diet At day 7 of week of estradiol administration on low-salt diet Aldosterone levels in women on placebo on high-salt diet At days 6 and 7 of week of placebo administration on high-salt diet Aldosterone levels in women on placebo on low-salt diet At day 7 of week of placebo administration on low-salt diet Urinary sodium concentration in women on estradiol on high-salt diet 0, 60, and 120 minute of saline infusion on morning of day 7 of estradiol administration on high-salt diet Urinary sodium concentration in women on placebo on high-salt diet 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet Urinary sodium concentration in men on testosterone on high-salt diet 0, 60, and 120 minute of saline infusion on morning of day 7 of testosterone administration on high-salt diet Urinary sodium concentration in men on placebo on high-salt diet 0, 60, and 120 minute of saline infusion on morning of day 7 of placebo administration on high-salt diet
Trial Locations
- Locations (1)
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States