Sex Steroids Balance for Metabolic and Reproductive Health in Klinefelter Syndrome (KLIN-HEALTH)

May 7, 2026 updated by: Georgios Papadakis

Dissecting the Importance of Sex Steroids Balance for Metabolic and Reproductive Health in Men With Klinefelter Syndrome: a Randomized Controlled Study

The study seeks primarily to determine whether modulation of systemic and testicular sex steroids balance by aromatase inhibitors will positively affect the metabolic health and spermatogenesis of men with Klinefelter syndrome (KFS) as compared to the current state of the art for each issue.

Secondary objectives of this study are (i) to unravel the heterogeneity of the reproductive and metabolic phenotype of men with KFS by performing a multi-omic analysis in a large cohort at baseline; (ii) to evaluate the efficacy of semaglutide-induced weight loss to achieve metabolic and reproductive benefit in men with Klinefelter syndrome as compared to standard testosterone replacement; (ii) to assess whether addition of hCG to aromatase inhibitors further increases intratesticular testosterone and promotes spermatogenesis in men with KFS.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Switzerland
      • Lausanne, Switzerland, 1011
        • Recruiting
        • Service of Endocrinology, Diabetes & Metabolism
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 65 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

-Diagnosis of Klinefelter syndrome (47,XXY or mosaicism)

Design 1:

  • Age range: 16-40 years old
  • Intention to become parent or interest in fertility preservation
  • Confirmed azoospermia (lack of spermatozoids) after centrifugation of one semen sample

Design 2:

  • Age range: 18-65 years old
  • No interest in fertility or fertility preservation
  • Hypogonadism at diagnosis or after wash-out of testosterone replacement therapy
  • High metabolic risk defined as overweight (BMI 25-28 kg/m2) and insulin resistance (HOMA-IR > 2.6)

Exclusion Criteria:

  • Contraindications to testosterone-rising therapies (prostate or breast cancer, PSA > 4 µg/l, active liver disease, symptomatic heart disease)
  • Decreased life expectancy due to terminal disease
  • Known or suspected non-compliance, drug or alcohol abuse
  • Inability to follow the procedures of the study (language problems, severe psychological or mental disorders)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: Group 1 (Fertility) - positive micro-dissection testicular sperm extraction (mTESE) biopsy 1
Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have positive sperm retrieval (detectable spermatozoids)
Experimental: Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm A
Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have negative sperm retrieval (no detectable spermatozoids), subsequently randomized to receive an hormonal stimulation for 26 weeks
Drug: Anastrozole
This will be an experimental treatment for 26 weeks in Group 1 Arm A and Arm B as well for Group 2 Arm D
Other Names:
  • Anastrozole Teva
Experimental: Group 1 (Fertility) - negative mTESE biopsy 1, then randomized to Arm B
Men with Klinefelter syndrome seeking fertility or interested in fertility preservation that undergo mTESE biopsy after wash-out of testosterone replacement therapy and have negative sperm retrieval (no detectable spermatozoids), subsequently randomized to receive an hormonal stimulation for 26 weeks
Drug: Anastrozole
This will be an experimental treatment for 26 weeks in Group 1 Arm A and Arm B as well for Group 2 Arm D
Other Names:
  • Anastrozole Teva
Drug: human chorionic gonadotropin
This will be an experimental treatment for 26 weeks in addition to anastrozole in Group 1 - Arm B
Other Names:
  • Choriomon
Active Comparator: Group 2 (Metabolic Risk) - randomized to Arm C
Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an active comparator by a testosterone gel
Drug: Testosterone gel
This will be an active comparator for 26 weeks in Group 2 - Arm C
Other Names:
  • Tostran
Experimental: Group 2 (Metabolic Risk) - randomized to Arm D
Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an an experimental treatment
Drug: Anastrozole
This will be an experimental treatment for 26 weeks in Group 1 Arm A and Arm B as well for Group 2 Arm D
Other Names:
  • Anastrozole Teva
Experimental: Group 2 (Metabolic Risk) - randomized to Arm E
Men with Klinefelter syndrome not interested in fertility that present with high metabolic risk and consent to a wash-out of testosterone replacement therapy. They are subsequently randomized to receive an hormonal treatment to improve metabolic health. This arm will receive an an experimental treatment
Drug: Semaglutide
This will be an experimental treatment for 26 weeks in Group 2 Arm E
Other Names:
  • Ozempic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Design 1 : sperm retrieval rate at mTESE biopsy
Time Frame: mTESE biopsy 26 weeks after hormonal intervention
Sperm retrieval rate at mTESE biopsy (Group A and B)
mTESE biopsy 26 weeks after hormonal intervention
Design 2 : change in insulin resistance index (HOMA-IR)
Time Frame: From baseline to week 26 of intervention
HOMA-IR calculated using fasting glucose and insulin levels
From baseline to week 26 of intervention

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Georgios Papadakis

Investigators

  • Principal Investigator: GEORGIOS PAPADAKIS, MD, Service of endocrinology, diabetes & metabolism, CHUV, Lausanne University Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2023

Primary Completion (Estimated)

April 30, 2027

Study Completion (Estimated)

April 30, 2027

Study Registration Dates

First Submitted

October 15, 2022

First Submitted That Met QC Criteria

October 15, 2022

First Posted (Actual)

October 19, 2022

Study Record Updates

Last Update Posted (Actual)

May 11, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PZ00P3_202151

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Upon reasonable request and data transfer agreement

IPD Sharing Time Frame

At study completion

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Klinefelter Syndrome

Clinical Trials on Anastrozole

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Guinea

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe