Comparative Effects of Nebivolol and Metoprolol on Female Sexual Function

Beta-blockers (BB) are an important treatment for high blood pressure and heart disease. However beta-blockers can cause sexual dysfunction (SD) and this common side effect limits successful use of this class of medications. Sexual side effects often result in drug discontinuation, compromising therapy goals. The investigators are conducting the study to determine if nebivolol, a newer beta blocker that is selective for receptors in the heart and causes vasodilation in the body causes fewer sexual side effects, or even improves sexual function, compared with metoprolol succinate.

Study Overview

• Status: Completed
• Conditions: Hypertension; Female Sexual Dysfunction
• Intervention / Treatment: Drug: nebivolol and metoprolol succinate; Drug: metoprolol succinate and nebivolol

Detailed Description

This protocol is designed to compare the effects two beta blockers, nebivolol (Bystolic) 5-10 mg daily with metoprolol succinate (Toprol XL) 100-200 mg daily on sexual function in post-menopausal women with high blood pressure. The study is composed of 2 treatment phases. At baseline subjects are randomized to either nebivolol 5 mg once daily or metoprolol succinate 100 mg once daily. After randomization, subjects are treated for 12 weeks with double blind therapy. Following double-blind therapy subjects enter a 2-week washout phase and are subsequently switched to the alternate therapy.

After 4 weeks (visits 3 and 7) of double-blind treatment with either nebivolol 5 mg once daily or metoprolol succinate 100 mg once daily subjects will be evaluated and the need for dosage titration assessed. If blood pressure is not at goal the dosage of study medication will be doubled to nebivolol 10 mg once daily or metoprolol succinate 200 mg once daily. If blood pressure remains uncontrolled after 8 weeks of double blind treatment with study medication open label amlodipine 5 mg will be initiated (visits 4 and 8) at the discretion of the principal investigator. During double blind treatment subjects will be evaluated in clinic every 4 weeks.

The primary efficacy variable is the change from baseline in Changes in Sexual Functioning Questionnaire (CSFQ) and the Female Sexual Function Index (FSFI).

The primary study objective is to determine whether nebivolol causes fewer sexual side effects compared with metoprolol succinate and if nebivolol improves FSF in women. FSF will be assessed with the above questionnaires-FSFI and CSFQ.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Family Practice

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Over the age of 40 years
2. Postmenopausal (according to self report of 12 consecutive months of amenorrhea, serum FSH concentrations greater than 40 international units/L, or surgical history consistent with menopause)
3. In a stable monogamous relationship with a male partner for at least 6 months
4. History of hypertension, treated or untreated
5. Requirement for the initiation of an anti-hypertensive agent OR addition of another anti-hypertensive medication (according to the principal investigator and based on clinical judgment) OR patients requiring monotherapy with an anti-hypertensive that wish to participate in the study and are willing to undergo a two week wash-out of current anti-hypertensive therapy
6. Provide written informed consent prior to participation.

Exclusion Criteria:

1. Properly measured clinic SBP > 170 mmHg
2. Advanced AV block
3. Severe hepatic disease
4. Heart rate < 55 beats/min (and not currently on beta blocker therapy)
5. Pregnancy or lactation
6. Heart failure with ejection fraction less than 0.40
7. History of myocardial infarction
8. History of Raynaud's syndrome
9. Patients with alcoholism or recreational drug use will be excluded due to concerns about the ability to comply with the study requirements.
10. Major psychiatric disorder not well controlled with treatment
11. Spinal cord injury
12. Severe respiratory disease, which in the opinion of the investigator contraindicates BB treatment
13. Poorly controlled diabetes mellitus (≥ 9%)
14. Persistent arrhythmia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Nebivolol 5 mg daily for 12 weeks followed by Metoprolol succinate 100 mg daily for 12 weeks. A two week washout (no medication) is completed prior to switching to metoprolol.	Drug: nebivolol and metoprolol succinate; Subjects randomized to treatment Arm A will receive nebivolol 5 mg once daily for 12 weeks. After 12 weeks, double blind therapy will be discontinued and patients will undergo a wash-out period of study therapy over 2 weeks. Subjects randomized to treatment Arm A will then receive metoprolol succinate 100 mg once daily. Subjects will continue double blind therapy for a total duration of 12 weeks.; Other Names: Bystolic; Toprol XL; nebivolol; metoprolol succinate
Experimental: Arm B; Metoprolol succinate 100 mg daily for 12 weeks followed by nebivolol 5 mg daily for 12 weeks. A two week washout (no medication) is completed prior to switching to nebivolol.	Drug: metoprolol succinate and nebivolol; Subjects randomized to treatment Arm B will receive metoprolol succinate 100mg once daily for 12 weeks. After 12 weeks, double blind therapy will be discontinued and patients will undergo a wash-out period of study therapy over 2 weeks. Subjects randomized to treatment Arm B will then receive nebivolol 5 mg once daily. Subjects will continue double blind therapy for a total duration of 12 weeks.; Other Names: Bystolic; Toprol XL; nebivolol; metoprolol succinate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Female Sexual Function Index	This scale is a self-reported instrument used to detect female sexual function. The scale ranges from 2 to 36. The higher score indicates higher sexual function.	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Sexual Functioning Questionnaire Score	This scale is a self-reported instrument used to detect sexual functioning. The scale ranges from 14 to 70. The higher scores reflects higher sexual functioning.	Baseline, 12 weeks

Collaborators and Investigators

• Sponsor: East Coast Institute for Research
• Investigators: Principal Investigator: Benjamin Epstein, PharmD, East Coast Institute for Research

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: October 1, 2009
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: October 12, 2009
• First Submitted That Met QC Criteria: October 13, 2009
• First Posted (Estimate): October 14, 2009

Study Record Updates

• Last Update Posted (Actual): March 29, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: hypertension; female; sexual dysfunction; nebivolol; high blood pressure; metoprolol; beta blockers; Bystolic; Toprol XL
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic Agonists; Adrenergic beta-Agonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Adrenergic beta-1 Receptor Agonists; Nebivolol; Metoprolol
• Other Study ID Numbers: SAIRB-09-0011