Female Sexual Dysfunction, Hypertension
Conditions
Keywords
sexual dysfunction, female, hypertension, high blood pressure, beta blockers, metoprolol, nebivolol, Bystolic, Toprol XL
Brief summary
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.
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.
Interventions
DRUGnebivolol 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.
DRUGmetoprolol 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.
Sponsors
East Coast Institute for Research
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Female Sexual Function Index | Baseline, 12 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Sexual Functioning Questionnaire Score | Baseline, 12 weeks | 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. |
Countries
United States
Participant flow
Pre-assignment details
4 subjects were randomized and dropped from the study prior to taking the study medication
Participants by arm
| Arm | Count |
|---|---|
| Nebivolol 5 mg Daily First, Then Metoprolol Succinate 100 mg 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.
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. | 9 |
| Metoprolol Succinate 100 mg First, Then Nebivolol 5 mg Daily 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.
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. | 12 |
| Total | 21 |
Baseline characteristics
| Characteristic | Metoprolol Succinate 100 mg First, Then Nebivolol 5 mg Daily | Total | Nebivolol 5 mg Daily First, Then Metoprolol Succinate 100 mg |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 3 Participants | 4 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 17 Participants | 8 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 12 Participants | 21 Participants | 9 Participants |
| Sex: Female, Male Female | 12 Participants | 21 Participants | 9 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 25 | 0 / 25 |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
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.
Time frame: Baseline, 12 weeks
Population: The number of participants analyzed for the measure are participants that had data available for both of the study periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol 5 mg Daily | Change in Female Sexual Function Index | 1.24 units on a scale | Standard Deviation 9.183 |
| Metoprolol Succinate 100 mg Daily | Change in Female Sexual Function Index | 1.42 units on a scale | Standard Deviation 5.262 |
Secondary
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.
Time frame: Baseline, 12 weeks
Population: The number of participants analyzed for the measure are participants that had data available for both of the study periods.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nebivolol 5 mg Daily | Change in Sexual Functioning Questionnaire Score | 2.38 units on a scale | Standard Deviation 7.6 |
| Metoprolol Succinate 100 mg Daily | Change in Sexual Functioning Questionnaire Score | 0.85 units on a scale | Standard Deviation 8.315 |