Hypertension
Conditions
Keywords
Natriuretic Peptides
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.
Interventions
DRUGleuprolide acetate
Given to both arms to induce hypogonadism
DRUGAnastrozole
Given to men to prevent conversion of administered testosterone to estradiol.
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 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 | — |
| 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 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 | — |
Countries
United States
Outcome results
None listed