A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial

Rigshospitalet

Status and phase: Terminated; Phase 4

Conditions: Hypogonadotropic Hypogonadism; Hypogonadism; Hypogonadism, Male

Treatments: Drug: Placebo; Drug: Letrozole 2.5mg, hCG

Study type: Interventional

Funder types: Other

Identifiers

NCT05205837

H-20036287

2020-002612-52 (EudraCT Number)

Details and patient eligibility

About

The overall objective of this randomized trial is to investigate the effects of treatment of AAS- induced male hypogonadism with combined therapy of letrozole and hCG compared with placebo on reproductive hormone levels, adherence to cessation of AAS use, fertility, cardiac function and quality of life.

Full description

A randomized, double-blinded, clinical, placebo-controlled trial enrolling 60 male illicit AAS users with documented AAS-induced hypogonadism after a period > 12 weeks of AAS cessation or a negative urine AAS doping test. Participants will be randomized to two study groups; 24 weeks of treatment with either tablet letrozole (femar®) initial dose of 2.5 mg each day versus tablet placebo. After an initial treatment period of four weeks, intramuscular injections with either hCG, initial dose 1500 IE twice weekly (letrozole group) or isotonic saline twice weekly (placebo group) will be added to therapy if plasma total testosterone level has not increased to target plasma level. Following 24 weeks of therapy, all participants will be observed for another 26 weeks without therapy. The study will have one trial center of recruitment: Department of Endocrinology, Rigshospitalet. Following participation in the study, all participants will be offered referral to an endocrine outpatient clinic if they still display clinical and biochemical signs of male hypogonadism.

A healthy group of 30 young lean eugonadal men, who have never used AAS, will be enrolled as control participants and undergo a screening visit and one visit including same procedures as the screening and randomization visits.

Enrollment: 8 patients

Sex: Male

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• • Male sex

  • 18 - 50 years of age
  • Hypogonadism following observational period of a minimum of 12 weeks since AAS discontinuation OR hypogonadism with a urine sample negative for AAS analyses at screening visit: plasma total testosterone ≤ 10 nmol/L AND featuring at least one symptom of male hypogonadism using IIEF in terms of erectile function (IIEF: Q1 - Q5 + Q15; total score < 26) and/or sexual desire (IIEF: Q11 + Q12; total < 7) (1) and/or ADAM questionnaire (YES to three questions other than question 1 and 7) and/or regular use of medical treatment for erectile dysfunction.
  • Motivation for permanent AAS cessation

Exclusion criteria

• Established cardiovascular disease

  • Established diabetes of any kind 384
  • Congenital hypogonadal conditions (cryptorchidism, Klinefelter's disease, Kallmann's disease etc.)
  • Previous established hypogonadal conditions due to other causes than illicit use of AAS
  • Current or previous treatment with testosterone on other indication than AAS-induced male hypogonadism
  • Abnormal puberty development (small testes, late or absent pubic hairing, late or absent deepening of voice, etc.)
  • Current or previous pituitary diseases including pituitary tumors
  • Current or previous tumors of the hypothalamus
  • Current or former testicular cancer
  • Current or previous prostate cancer
  • Current or previous breast cancer
  • Other cancers unless complete remission ≥ 5 year
  • Other concomitant disease or makes the patient unsuitable to participate in the study
  • Severely impaired liver function
  • Allergy or hypersensitivity to the active substance (letrozole) or excipients of Letrozol "Accord"® listed in Appendix D
  • Allergy or hypersensitivity to the active substance (hCG) or excipients of Brevactid® listed in Appendix D
  • Established Lapp lactase deficiency or glucose/galactose malabsorption
  • Severe venous phlebitis or current or previous venous thromboembolism
  • Inguinal hernia
  • treatment which according to the investigators' assessment
  • Simultaneous participation in another clinical study
  • Unable to follow treatment instructions in terms of study medication instructions
  • Ongoing criminal behavior in terms of violence or illicit distribution of drugs
  • Currently or in the foreseeable future included in anti-doping programs

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

8 participants in 2 patient groups, including a placebo group

Active Comparator - placebo

Placebo Comparator group

Description:

Intervention: Intramuscular injection - placebo Intervention: Drug: placebo

Treatment:

Drug: Placebo

Active comparator - treatment

Active Comparator group

Description:

Intervention: intramuscular injection - hCG Intervention: Drug: Letrozole

Treatment:

Drug: Letrozole 2.5mg, hCG