Therapy With Letrozole and hCG in Male Hypogonadism Induced by Illicit Use of AAS

[madman]

ClinicalTrials.gov

clinicaltrials.gov

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​

Brief Summary

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.


Detailed 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: the Department of Endocrinology, Rigshospitalet. Following participation in the study, all participants will be offered a 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 the same procedures as the screening and randomization visits.

Primary Outcome Measures :

1. Change in plasma total testosterone concentration after 24 weeks from baseline [ Time Frame: 24 weeks ]

Secondary Outcome Measures :

1. Number of participants who adhere to AAS cessation after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
2. Change in total plasma testosterone concentration after 50 weeks from baseline [ Time Frame: 50 weeks ]
3. Change in plasma total testosterone secretion in response to hCG stimulation after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
4. Change in basal plasma pituitary gonadotropins, LH and FSH, after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
5. Change in secretion of plasma pituitary gonadotropins, LH and FSH, in response to GnRH stimulation after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
6. Change in sperm count after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
7. Change in sperm motility after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
8. Change in sperm morphology after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
9. Change in sperm acrosome reaction after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
10. Change in sperm DNA fragmenting after 24 and 50 weeks from baseline [ Time Frame: 24 and 50 weeks ]
11. Change in testicular size assessed using ultrasound after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
12. Change in questionnaire score IIEF (erectile function and libido) from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
13. Change in questionnaire score ADAM (hypogonadism) from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
14. Change in questionnaire score of Major Depression Inventory (MDI) (depression) from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
15. Change in questionnaire score of (GAD7) (anxiety) from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
16. Change in questionnaire score of Buss-Perry Aggression scale (BPA) (hostility and aggression) from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
17. Change in questionnaire score of COBRA (Cognitive complaints in bipolar disorder rating assessment) from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
18. Change in questionnaire score of the Health Assessment Short Form-36 questionnaire from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
19. Change in questionnaire score of Body-Q 349 (Perception of own body) from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
20. Change in questionnaire score of the Inventory of Interpersonal Problems 32-item (IIP32) from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
21. Change in myocardial function assessed by myocardial flow reserve (mL/min/gr) by Rb-82 PET from baseline and after 24 and 50 weeks [ Time Frame: 24 and 50 weeks ]
22. Change in cardiac systolic function was assessed using left ventricular ejection fraction (LVEF) obtained using echocardiography and 24 and 50 weeks from baseline. [ Time Frame: 24 and 50 weeks ]
23. Change in cardiac systolic function was assessed using left ventricular global longitudinal strain (GLS) obtained using echocardiography and 24 and 50 weeks from baseline. [ Time Frame: 24 and 50 weeks ]
24. Change in cardiac structure (left ventricular mass) obtained using echocardiography and 24 and 50 weeks from baseline. [ Time Frame: 24 and 50 weeks ]