What side effects are associated with this type of intervention?

Clomiphene Citrate, used to treat low testosterone, can cause side effects such as visual disturbances, mood swings, and potential increases in liver enzymes. Other common treatments like testosterone replacement therapy (TRT) may lead to side effects including erythrocytosis, acne, sleep apnea, and an increased risk of cardiovascular events. Patients should discuss these potential risks with their healthcare provider to determine the most appropriate treatment.

What prior FDA approvals exist?

The FDA has approved several treatments for low testosterone, primarily focusing on testosterone replacement therapies such as testosterone gels, patches, injections, and pellets. These treatments directly supplement testosterone levels rather than stimulating the body's own production. Clomiphene Citrate, a Selective Estrogen Receptor Modulator (SERM), is not FDA-approved for treating low testosterone but is sometimes used off-label to stimulate gonadotropin release and increase endogenous testosterone production. Other similar treatments include aromatase inhibitors, which also work to increase endogenous testosterone by preventing the conversion of testosterone to estrogen, though these are not typically first-line treatments for low testosterone.

What other types of research exist?

Promising alternatives to Clomiphene Citrate for low testosterone patients include aromatase inhibitors (such as anastrozole or letrozole) and GnRH antagonists (such as degarelix). These treatments have shown efficacy in increasing testosterone levels by different mechanisms: aromatase inhibitors prevent the conversion of testosterone to estrogen, and GnRH antagonists suppress the release of gonadotropins from the pituitary gland.

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Selective Estrogen Receptor Modulator

Clomiphene Citrate for Low Testosterone

Q: What is the mechanism of action of this treatment?

Common treatments for low testosterone include Clomiphene Citrate, testosterone replacement therapy (TRT), and aromatase inhibitors. Clomiphene Citrate, a Selective Estrogen Receptor Modulator (SERM), works by stimulating the release of gonadotropins (LH and FSH) from the pituitary gland, which in turn increases the production of testosterone by the testes. This is particularly important for patients with low testosterone as it helps restore natural testosterone production without directly introducing external testosterone, potentially preserving fertility. TRT involves the direct administration of testosterone, which can quickly alleviate symptoms but may suppress natural testosterone production and affect fertility. Aromatase inhibitors reduce the conversion of testosterone to estrogen, thereby increasing testosterone levels. Understanding these mechanisms helps patients and doctors choose the most appropriate treatment based on individual needs and long-term health goals.

Phase 2

Recruiting

Led By Jonathan Gal, MD

Research Sponsored by Weill Medical College of Cornell University

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Male, 21-45 years of age

Serum testosterone concentration < 300 ng/dl measured on two separate occasions (separated by at least one week), with collection prior to 10AM

Must not have

History of pituitary tumor or resection of pituitary tumor

Documented allergy or hypersensitivity to clomiphene citrate or other SERM

Timeline

Screening 3 weeks

Treatment Varies

Follow Up evaluation will occur at baseline, day 2, day 4, weeks 1 - 4, and again at weeks 8, 12, and 16.

Awards & highlights

Summary

This trial tests clomiphene citrate in men with low testosterone to see if it can naturally boost their hormone levels. The goal is to find a dose that doesn't require daily medication. Clomiphene citrate has been used to increase testosterone levels in men and improve reproductive health.

Who is the study for?

Men aged 21-45 with low testosterone (TT < 300 ng/dl) can join this trial. They must have had two tests a week apart showing low levels and be free from serious health issues like heart or liver disease, psychiatric disorders, bleeding problems, and certain hormonal conditions. No history of drug abuse or sensitivity to clomiphene is allowed.

What is being tested?

The trial is testing how the body processes two different doses of Clomiphene Citrate (25mg and 50mg) in men with low testosterone. Participants will be randomly assigned to receive one of the doses in an open-label setting where both they and the researchers know which dose is given.

What are the potential side effects?

Clomiphene Citrate may cause side effects such as vision changes, mood swings, pain in the testes, flushing, nausea, vomiting, headache. It's important for participants to report any discomforts they experience during the trial.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am a man aged between 21 and 45.

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My testosterone levels are below 300 ng/dl, confirmed by two tests.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a pituitary tumor or surgery to remove one.

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I am allergic to clomiphene or similar medications.

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I have had testicular cancer or have undergone orchiectomy.

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I have been diagnosed with primary hypogonadism.

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I have had prostate cancer or severe prostate enlargement.

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I have had chemotherapy, radiation to my groin/pelvis, or been exposed to agents harmful to reproductive organs.

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I have had inflammation of the testicle or epididymis before.

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I have a health condition like kidney, heart, liver disease, or others listed.

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My tests show an abnormal chromosome structure.

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I have been diagnosed with Kallmann syndrome.

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I have had a urinary tract infection before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ evaluation will occur at baseline, day 2, day 4, weeks 1 - 4, and again at weeks 8, 12, and 16.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~evaluation will occur at baseline, day 2, day 4, weeks 1 - 4, and again at weeks 8, 12, and 16.

This trial's timeline: 3 weeks for screening, Varies for treatment, and evaluation will occur at baseline, day 2, day 4, weeks 1 - 4, and again at weeks 8, 12, and 16. for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in serum testosterone

Secondary study objectives

Change in FSH levels

Body Weight Changes

Change in estradiol levels

Trial Design

2Treatment groups

Experimental Treatment

Group I: Clomiphene citrate 50 mg every other day for 12 weeksExperimental Treatment1 Intervention

Group II: Clomiphene citrate 25 mg daily for 12 weeksExperimental Treatment1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Clomiphene Citrate 50mg

2021

Completed Phase 4

~430

Clomiphene Citrate 25mg

2015

Completed Phase 2

~30

0 / 13Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for low testosterone include Clomiphene Citrate, testosterone replacement therapy (TRT), and aromatase inhibitors. Clomiphene Citrate, a Selective Estrogen Receptor Modulator (SERM), works by stimulating the release of gonadotropins (LH and FSH) from the pituitary gland, which in turn increases the production of testosterone by the testes. This is particularly important for patients with low testosterone as it helps restore natural testosterone production without directly introducing external testosterone, potentially preserving fertility. TRT involves the direct administration of testosterone, which can quickly alleviate symptoms but may suppress natural testosterone production and affect fertility. Aromatase inhibitors reduce the conversion of testosterone to estrogen, thereby increasing testosterone levels. Understanding these mechanisms helps patients and doctors choose the most appropriate treatment based on individual needs and long-term health goals.