Aromatase Inhibitors in the Treatment of Male Infertility

This study has been terminated.
(Not able meet target enrollment.)
Sponsor:
Information provided by (Responsible Party):
Ahmad Hammoud, University of Utah
ClinicalTrials.gov Identifier:
NCT00440180
First received: February 22, 2007
Last updated: May 20, 2014
Last verified: May 2014
  Purpose

Obesity is associated with an increase in blood levels of estrogen. Estrogen or "female hormone" is believed to have a negative effect on sperm production. Aromatase inhibitors such as anastrozole work to decrease the production of estrogen and increase testosterone in the body. By decreasing the level of estrogen, sperm production should improve. In this study, the investigators will try to determine the benefit of anastrozole in obese men with low sperm counts.

Patients participating in this study will be randomly assigned (by chance) to treatment in one of two study arms: Group A: Anastrozole 1mg per day for 4 months and Group B: Placebo for 4 months. Neither patients nor doctors will know in which treatment group they are.

Screening assessments will take place prior to the start of treatment. During this time, demographic data and medical history will be reviewed and recorded. Also, testicular exam, sperm count and laboratory blood analysis will be performed. Over the course of study, semen and blood analysis including hormonal profile (testosterone, estrogen, follicle stimulating hormone and luteinizing hormone) will be recollected.

At the conclusion of the trial, the investigators expect the group that received anastrozole to have an improved sperm count, increased testosterone and decreased estrogen levels.


Condition Intervention Phase
Obesity
Oligospermia
Drug: Anastrozole
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Role of Aromatase Inhibitors in the Treatment of Infertility in Obese Male

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Sperm concentration [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Other sperm parameters, hormonal measures and pregnancy rates [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: March 2007
Estimated Study Completion Date: June 2014
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Group B
Placebo
Drug: Placebo
Placebo Comparator
Other Name: Placebo
Experimental: Group A
Anastrozole
Drug: Anastrozole
1 mg qd for 4 months
Other Name: Arimidex

Detailed Description:

The role of aromatase inhibitors in the treatment of infertility (due to hypogonadism) in obese Male

Background:

The incidence of male infertility is increasing in the western world in parallel with an increase in obesity. It is estimated that in the United States sperm counts may be decreasing by as much as 1.5% each year (Swan et al, 2000). It is proposed that increased estrogen levels associated with obesity cause hypogonadism and male infertility via inappropriate suppression of gonadotropins and direct adverse effects on spermatogenesis. The link between obesity and its likely effects on the endocrine function of the male reproductive axis underlie the mechanistic justification for this novel trial of a medical therapy for hypogonadism and male infertility associated with obesity.

Study design:

The investigaotrs designed a double blind, randomized, placebo control trial of the aromatase inhibitor Anastrozole to treat men that are overweight (BMI ≥ 30 kg/m2) and oligospermic (sperm count ≤ 20 × 106/mL and ≥ than 3 × 106/mL). After enrollment, patients will be randomized to receive Anastrozole 1mg/d or placebo for 4 months. Semen analysis and hormonal profile (FSH, LH, Estradiol, total and free Testosterone will be measured at the start and the conclusion of the study. The primary outcome will be sperm density. Secondary outcomes will be other sperm parameters including: total count per ejaculate, total motile sperm per ejaculate, and sperm morphology. The investigators will also follow the change in FSH and LH, testosterone and estrogen levels, and will seek correlation between endocrine change and semen parameters. Based on a power analysis, a total of 50 patients will be included in the study. Study design and reporting will comply with the CONSORT (Consolidated Standards of Reporting Trials) guidelines.

Anticipated results:

The study will evaluate the research hypothesis that inhibition of aromatase will result in improvements in sperm density, as well as secondary semen analysis parameters (e.g. morphology and motility). Supporting endocrine data will be obtained as part of this clinical protocol that the investigators expect will show an increase in testosterone, LH and FSH levels and a decrease in estrogen levels associated with active treatment.

  Eligibility

Ages Eligible for Study:   16 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male partner of a couple presenting for infertility work up after one year of unprotected intercourse
  2. Moderate oligozoospermia (defined as mean sperm count ≤ 20 × 106/mL and ≥ than 3 × 106/mL) of at least two separate occasions spanning a minimum of two weeks
  3. Obese men BMI ≥ 30
  4. FSH and LH levels < 10 mIU/mL

Exclusion Criteria:

  1. Severe Oligozoospermia: Sperm count < than 3 × 106/mL, including azoospermia
  2. Age less than 18 or greater than 65 years
  3. Pyospermia or leukospermia: defined by white blood cells ≥ 1 million leukocytes per milliliter of semen
  4. Cryptorchidism
  5. Vasectomy reversal
  6. Regular use of tobacco products
  7. BMI < 30
  8. Use of anabolic steroids or testosterone replacement
  9. All patients with abnormal initial liver function tests "AST or ALT" will be excluded form the study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00440180

Locations
United States, Utah
University of Utah
Salt Lake City, Utah, United States, 84132
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: Ahmad O Hammoud, MD University of Utah
  More Information

No publications provided

Responsible Party: Ahmad Hammoud, MD, University of Utah
ClinicalTrials.gov Identifier: NCT00440180     History of Changes
Other Study ID Numbers: IRB_00016246
Study First Received: February 22, 2007
Last Updated: May 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Utah:
Obesity
Low sperm count
Male infertility

Additional relevant MeSH terms:
Obesity
Infertility
Oligospermia
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Genital Diseases, Male
Genital Diseases, Female
Infertility, Male
Aromatase Inhibitors
Anastrozole
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 30, 2014