Combined Antihypertensive Therapy and Sexual Dysfunction

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

This randomized,active controlled study aimed to compare the effects on sexual function of treatment with combined antihypertensive drugs.

The researchers hypothesize that:

1. Both felodipine-irbesartan combination and felodipine-metoprolol combination are effective in lowing blood pressure in patients with essential hypertension.
2. 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.
3. Oxidative stress decline after both combination regimens. Felodipine-irbesartan combination has a greater impact on oxidative stress indicators than felodipine-metoprolol combination.

Study Overview

• Status: Unknown
• Conditions: Hypertension; Sexual Dysfunction
• Intervention / Treatment: Drug: Felodipine add Irbesartan; Drug: Felodipine add Metoprolol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 280
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jing Yu, Professor; Phone Number: +86 0931 8942076; Email: yujing2304@126.com
• Study Contact Backup: Name: Ruixin Ma, Doctor; Phone Number: +86 13893102690; Email: mrxdr@sina.com

Study Locations

• China
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • Recruiting
      • The Second Hospital of Lanzhou University
      • Contact: Ruixin Ma, Doctor; Phone Number: +86 13893102690; Email: mrxdr@sina.com
      • Contact: Jing Yu, Professor; Phone Number: +86 13893607559; Email: yujing2304@126.com
      • Principal Investigator: Jing Yu, Professor
      • Sub-Investigator: Ruixin Ma, Doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Felodipine,Irbesartan,Sexual Dysfunction	Drug: Felodipine add Irbesartan; Felodipine Sustained Release Tablets,5mg/day,AstraZeneca Pharmaceutical Co.Ltd., Registration Number: H20030415. Irbesartan,150mg/day, Sanofi - Aventis Pharmaceutical company, Registration Number: H20080074.; Other Names: Plendil; Aprovel
Active Comparator: Felodipine,Metoprolol,Sexual Dysfunction	Drug: Felodipine add Metoprolol; 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.; Other Names: Betaloc; Plendil

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: LanZhou University
• Investigators: Study Chair: Jing Yu, Professor, Second Hospital of Lanzhou University

Publications and helpful links

General Publications

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• Fogari R, Preti P, Derosa G, Marasi G, Zoppi A, Rinaldi A, Mugellini A. Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men. Eur J Clin Pharmacol. 2002 Jun;58(3):177-80. doi: 10.1007/s00228-002-0456-3. Epub 2002 May 1.
• Fogari R, Zoppi A, Corradi L, Mugellini A, Poletti L, Lusardi P. Sexual function in hypertensive males treated with lisinopril or atenolol: a cross-over study. Am J Hypertens. 1998 Oct;11(10):1244-7. doi: 10.1016/s0895-7061(98)00139-3.
• Dusing R. Sexual dysfunction in male patients with hypertension: influence of antihypertensive drugs. Drugs. 2005;65(6):773-86. doi: 10.2165/00003495-200565060-00005.
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• Ma R, Yu J, Xu D, Yang L, Lin X, Zhao F, Bai F. Effect of felodipine with irbesartan or metoprolol on sexual function and oxidative stress in women with essential hypertension. J Hypertens. 2012 Jan;30(1):210-6. doi: 10.1097/HJH.0b013e32834e1e2e.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Anticipated): October 1, 2010
• Study Completion (Anticipated): November 1, 2010

Study Registration Dates

• First Submitted: October 12, 2010
• First Submitted That Met QC Criteria: November 10, 2010
• First Posted (Estimate): November 11, 2010

Study Record Updates

• Last Update Posted (Estimate): November 11, 2010
• Last Update Submitted That Met QC Criteria: November 10, 2010
• Last Verified: November 1, 2010

More Information

Terms related to this study

• Keywords: Hypertension; Oxidative Stress; Combination; Antihypertensive Agents; Sexual Dysfunction
• 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; Membrane Transport Modulators; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Sympatholytics; Adrenergic beta-1 Receptor Antagonists; Metoprolol; Felodipine; Irbesartan
• Other Study ID Numbers: 0709TCYA068