Study of the Effect of Testosterone and Estradiol on NP Responses to Acute and Chronic Salt Loading

Mass General Brigham

Status and phase: Withdrawn; Early Phase 1

Conditions: Hypertension

Treatments: Drug: Anastrozole; Drug: leuprolide acetate

Study type: Interventional

Funder types: Other

Identifiers

NCT01763541

2012P002337

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 40 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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0 participants in 2 patient groups

Testosterone

Other group

Description:

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

Treatment:

Drug: leuprolide acetate

Drug: Anastrozole

Estradiol

Other group

Description:

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

Treatment:

Drug: leuprolide acetate