What side effects are associated with this type of intervention?

Common treatments for Hypogonadotropic Hypogonadism (HH) include gonadotropin-releasing hormone (GnRH) therapy, gonadotropin injections, and clomiphene citrate. Side effects of these treatments can vary. GnRH therapy may cause headaches, mood swings, and injection site reactions. Gonadotropin injections can lead to ovarian hyperstimulation syndrome (OHSS) in women, multiple pregnancies, and injection site discomfort. Clomiphene citrate may cause hot flashes, abdominal discomfort, and visual disturbances. Opioid antagonists, which are being studied for their potential to influence GnRH release, may cause gastrointestinal issues, headaches, and dizziness. It is important to discuss these potential side effects with a healthcare provider to determine the best treatment plan.

What prior FDA approvals exist?

The FDA has approved several treatments for Hypogonadotropic Hypogonadism (HH) that focus on stimulating the release of gonadotropin-releasing hormone (GnRH) or directly supplementing deficient hormones. Common treatments include gonadotropin therapy (e.g., human chorionic gonadotropin, hCG, and follicle-stimulating hormone, FSH) and pulsatile GnRH therapy, which directly stimulates the pituitary gland to release LH and FSH. While specific FDA approvals for opioid antagonists in the treatment of HH are not detailed, these drugs work by blocking opioid receptors, potentially influencing GnRH release and restoring normal hormonal function.

What other types of research exist?

Promising novel alternatives to opioid antagonists for treating hypogonadotropic hypogonadism in 2024 include the use of Kisspeptin and GnRH agonists/antagonists such as buserelin and nafarelin. These treatments aim to stimulate the hypothalamic-pituitary-gonadal axis and enhance gonadotropin release.

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Gonadotropin-releasing Hormone Agonist

Opioid Antagonist Therapy for Low Testosterone

Phase 2

Waitlist Available

Led By Stephanie Seminara, MD

Research Sponsored by Stephanie B. Seminara, MD

Eligibility Criteria Checklist

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

Must have

For women: Not breastfeeding and not pregnant

Hemoglobin: Women - no less than 0.5 gm/dL below the lower limit of the reference range for normal women; Men - on adequate testosterone replacement therapy: normal male reference range, off testosterone replacement therapy: no lower than 0.5 gm/dL below the lower limit of the reference range for normal women

Timeline

Screening 3 weeks

Treatment Varies

Follow Up before and during treatment

Awards & highlights

Summary

This trial uses hormone injections and naloxone to study their effects on people with low reproductive hormone levels due to an unknown cause. Kisspeptin and GnRH help increase hormone production, while naloxone blocks opioid effects. The goal is to understand how these treatments affect hormone levels in these patients.

Who is the study for?

This trial is for adults with low testosterone or estradiol due to hypogonadotropic hypogonadism (HH), who are not currently seeking fertility, and have stable medical conditions. Participants should not be on medications affecting reproductive functions, have no history of severe medication reactions, and must pass certain blood tests.

What is being tested?

The study is testing the impact of opioid antagonists like naloxone on the hormonal axis in people with idiopathic HH. It aims to understand how blocking opioids affects hormones that control reproductive functions using substances such as kisspeptin and GnRH.

What are the potential side effects?

Potential side effects may include reactions at injection sites, changes in mood or energy levels, gastrointestinal discomfort, headaches, and possible alterations in hormone levels which could affect various bodily functions.

Eligibility Criteria

Inclusion Criteria

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

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I am not pregnant or breastfeeding.

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My hemoglobin levels are within the normal range for my gender.

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I have been diagnosed with hypogonadotropic hypogonadism and have low testosterone or estradiol levels.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ before and during treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~before and during treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and before and during treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Average change in Luteinizing Hormone (LH) pulse frequency

Secondary study objectives

Pulse Rate

Side effects data

From 2008 Phase 3 trial • 19 Patients • NCT00710385

18%

Mild Opioid Withdrawal

12%

urticaria

chest discomfort

vomiting

dizziness

100%

80%

60%

40%

20%

Study treatment Arm

Combined for All Study Conditions

Trial Design

1Treatment groups

Experimental Treatment

Group I: naloxoneExperimental Treatment1 Intervention

one period of frequent blood sampling with no medication administered; one period of frequent blood sampling with IV administration of naloxone (one bolus and an infusion over an up to 12-hour period.)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Naloxone

2014

Completed Phase 3

~1290

0 / 3Eligibility 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

Hypogonadotropic Hypogonadism (HH) is commonly treated with therapies that aim to restore the function of the hypothalamic-pituitary-gonadal axis. One such treatment involves the use of opioid antagonists, which block opioid receptors and thereby influence the release of gonadotropin-releasing hormone (GnRH). This blockade helps to increase the secretion of GnRH, which in turn stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are crucial for the production of sex steroids and gametogenesis. For HH patients, this mechanism is vital as it addresses the underlying hormonal deficiency, thereby improving symptoms and potentially restoring fertility.

Regulation of pituitary glycoprotein alpha-subunit secretion after administration of a luteinizing hormone-releasing hormone antagonist in normal men.Progestins increase endogenous opioid peptide activity in postmenopausal women.A mild ovarian stimulation strategy in women with poor ovarian reserve undergoing IVF: a multicenter randomized non-inferiority trial.