Combined Antihypertensive Therapy and Sexual Dysfunction

Study Overview
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Brief Summary
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This randomized,active controlled study aimed to compare the effects on sexual function of treatment with combined antihypertensive drugs. The researchers hypothesize that: Both felodipine-irbesartan combination and felodipine-metoprolol combination are effective in lowing blood pressure in patients with essential hypertension. Felodipine-metoprolol combination induces a worse sexual function and a reduction of sex hormone,whereas felodipine-irbesartan combination does not impair sexual function and does not change hormone levels. Oxidative stress decline after both combination regimens. Felodipine-irbesartan combination has a greater impact on oxidative stress indicators than felodipine-metoprolol combination.

Detailed Description
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The effects of hypertension and its pharmacotherapy on sexual function are well known in men,although this topic remains unexplored in women.There is evidence suggests that some classes of antihypertensive drugs such as diuretics and beta-blockers have more negative impact on male sexual function than other classes such as calcium channel blockers(CCBs) and angiotensin-converting enzyme inhibitors(ACEI).Some data suggest that angiotensin Ⅱ antagonists（ARBs) not only do not exacerbate sexual function in males,but even improve it. Treatment with multiple antihypertensive medications was often necessary to attain blood-pressure goals recommended by guidelines.More than two third of patients with 2 or 3 degree of essential hypertension require combination therapy at the beginning of treatment to avoid target organ damage and to minimize the accidence of adverse events. CCBs were recommended by both JNC-7 and ESH / ESC 2007 hypertension guidelines as the basic for the treatment of hypertension.The purpose of this study is to compare the impacts of different CCB-based antihypertensive drugs combination on sexual behavior in both male and female patients with essential hypertension,thus provide evidences for physicians to increase patients adherence to the treatment regimens beside lowing blood pressure.

Official Title
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Effect of Combined Antihypertensive Therapy on Blood Pressure and Sexual Function in Patients With Essential Hypertension

Conditions
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Hypertension, Sexual Dysfunction

Intervention / Treatment
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* Drug: Felodipine add Irbesartan
* Drug: Felodipine add Metoprolol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with essential hypertension. Initial hypertension, or without taking any antihypertensive for at least one month. Sexual active. Exclusion Criteria: Patients with secondary hypertension. Patients with malignant hypertension, coronary heart disease, diabetes, a history of syncope, bradycardia (heart rate <45 beats / min), atrioventricular block(Ⅱ or Ⅲ degree), sick sinus syndrome, congestive heart failure, a history of cerebral vascular accidents, serious hepatic and kidney dysfunction, a history of serious mental illness, pregnant, taking oral exogenous estrogens (including contraceptives), hysterectomy, breastfeeding, a history of alcohol or drug abuse, having serious conflict with sexual partner, severity sexual dysfunction. Patients refuse to answer questions, refuse to fill in the questionaires,or do not willing to take blood examination.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Felodipine,Irbesartan,Sexual Dysfunction<br> | Drug: Felodipine add Irbesartan<br>* Felodipine Sustained Release Tablets,5mg/day,AstraZeneca Pharmaceutical Co.Ltd., Registration Number: H20030415. Irbesartan,150mg/day, Sanofi - Aventis Pharmaceutical company, Registration Number: H20080074.<br>* Other names: Aprovel;|
| Active Comparator: Felodipine,Metoprolol,Sexual Dysfunction<br> | Drug: Felodipine add Metoprolol<br>* Felodipine Sustained Release Tablets,5mg/day,AstraZeneca Pharmaceutical Co.Ltd., Registration Number: H20030415. Metoprolol Succinate,47.5mg/day,AstraZeneca Pharmaceutical Co.Ltd., Registration Number: J20050061.<br>* Other names: Betaloc;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Female Sexual Function Index (FSFI) | The Female Sexual Function Index (FSFI) is a multidimensional self-report scale for assessing sexual function in women.The FSFI hase been validated in women with various sexual disorders,and in non-dysfunctional controls showing good discriminant validity,internal consistency,and test-retest reliability. | 48 weeks | 
| International Index of Erectile Function(IIEF) | The 15-item International Index of Erectile Function (IIEF) was developed to diagnose the presence and severity of erectile dysfunction (ED). | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Systolic Blood Pressure in 2 Weeks | The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week. BP is measured using a calibrated standard mercury sphygmomanometer.After the patient has been seated for 15 minutes,sitting BP is measured 2 times at 1- to 2-minutes intervals,The mean of 2 sitting BP measurements is used as the sitting BP value for that visit;If the difference between the 2 measurements is over 5mmHg,BP should be measured again, and the average of 3 measurements will be taken. | 2 weeks | 
| Change of Systolic Blood Pressure in 4 Weeks | The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week. | 4 weeks | 
| Change of Systolic Blood Pressure in 8 Weeks | The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week. | 8 weeks | 
| Change of Systolic Blood Pressure in 12 Weeks | The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week | 12 weeks | 
| Change of Systolic Blood Pressure in 24 Weeks | The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week. | 24 weeks | 
| Change of Systolic Blood Pressure in 48 Weeks | The decrease of systolic blood pressure compared with baseline. Baseline is blood pressure in 0 week | 48 weeks | 
| Change of Diastolic Blood Pressure in 2 Weeks | The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week | 2 weeks | 
| Change of Diastolic Blood Pressure in 4 Weeks | The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week | 4 weeks | 
| Change of Diastolic Blood Pressure in 8 Weeks | The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week | 8 weeks | 
| Change of Diastolic Blood Pressure in 12 Weeks | The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week. | 12 weeks | 
| Change of Diastolic Blood Pressure in 24 Weeks | The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week. | 24 weeks | 
| Change of Diastolic Blood Pressure in 48 Weeks | The decrease of diastolic blood pressure compared with baseline. Baseline is blood pressure in 0 week. | 48 weeks | 
| Serum Estradiol in 24 Weeks | Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ℃. Use hemiluminescent radioimmunoassay to detect the level of estradiol in serum sample. | 24 weeks | 
| Serum Estradiol in 48 Weeks |  | 48 weeks | 
| Serum Testosterone in 24 Weeks | Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ℃. Use hemiluminescent radioimmunoassay to detect the level of testosterone in serum sample. | 24 weeks | 
| Serum Testosterone in 48 Weeks |  | 48 weeks | 
| Serum MDA in 24 Weeks | Among many oxidative stress biological indicators,malondialdehyde (MDA),the secondary products of lipid peroxidation,is the most representative and most studied polyunsaturated fatty acid peroxidation. Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ℃. Use ELISA to detect the level of MDA in serum samples. | 24 weeks | 
| Serum MDA in 48 Weeks |  | 48 weeks | 
| Serum 8-OHdG in 24 Weeks | Reactive oxygen species (ROS) produced either endogenously or exogenously can attack lipid, protein and nucleic acid simultaneously in the living cells. In nuclear and mitochondrial DNA, 8-hydroxydeoxyguanosine (8-OHdG) is produced during DNA repair and its measurement be useful as a marker of DNA lesion. Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ℃. Use ELISA to detect the level of 8-OHdG in serum samples. | 24 weeks | 
| Serum 8-OHdG in 48 Weeks |  | 48 weeks | 
| Serum HNE in 24 Weeks | 4 - hydroxy-nonyl acid (HNE) is a strong toxicity end product of lipid peroxidation. Fasting blood samples are taken at 8:00-10:00.After quiescence for 1h and centrifuged (3500rpm/min * 15min), serum samples are extracted and preserved in -80 ℃. Use ELISA to detect the level of HNE in serum samples. | 24 weeks | 
| Serum HNE in 48 Weeks |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertension, Antihypertensive Agents, Combination, Sexual Dysfunction, Oxidative Stress