In short
Leflutrozole is an investigational aromatase inhibitor being studied for male infertility. It is a chemically synthesised substance given as hard capsules by mouth. One authorised Phase 2 trial (2025-524774-42-00) is testing whether leflutrozole can improve semen quality in 15 men with non-obstructive azoospermia. A separate Phase 2 study reported a beneficial effect on sperm production in men with obesity-associated secondary hypogonadotropic hypogonadism.
Key points
- Leflutrozole is an investigational aromatase inhibitor with no marketing authorisation in the product records.
- A Phase 2 trial is testing leflutrozole in non-obstructive azoospermia, a form of male infertility.
- The trial is authorised and plans to enrol 15 participants.
- Leflutrozole is given as 0.3 mg hard capsules taken orally.
- The primary endpoint is the proportion of patients with spermatozoa in the ejaculate at Week 12–20.
- A separate Phase 2 study reported a beneficial effect on sperm production in men with obesity-associated hypogonadotropic hypogonadism.
What is leflutrozole?
Leflutrozole is a chemically synthesised substance classified as an aromatase inhibitor. Aromatase inhibitors block the enzyme aromatase, which converts testosterone to estradiol. Leflutrozole is an investigational substance: the product records from the EU Clinical Trials Information System (CTIS) show no marketing authorisation, meaning it has not been approved as a medicine for routine clinical use. The substance is supplied by Repronovo ApS.
How does leflutrozole work?
Leflutrozole works by inhibiting the aromatase enzyme. In men, aromatase converts testosterone into estradiol, a form of estrogen. Excess aromatase activity — for example in adipose (fat) tissue — can increase this conversion, leading to high estradiol levels and suppressed gonadotropins. This suppression can reduce sperm production and cause a condition called hypogonadotropic hypogonadism. By blocking aromatase, leflutrozole aims to lower estradiol and restore the hormonal signals that support sperm production.
Which conditions is it used or studied for?
Leflutrozole is not authorised for any condition. It is being studied in two areas of male infertility:
- Non-obstructive azoospermia — a condition where no sperm are present in the ejaculate because the testicles do not produce enough sperm. The authorised Phase 2 trial is testing whether leflutrozole can help sperm appear in the ejaculate.
- Obesity-associated secondary hypogonadotropic hypogonadism — a hormonal condition in men with obesity where high estradiol levels suppress the hormones that drive sperm production. A separate Phase 2 study reported a beneficial effect of leflutrozole on sperm production in this group.
How is leflutrozole given?
In the registered trial, leflutrozole is given as hard capsules containing 0.3 mg of the substance, taken orally (by mouth). No other pharmaceutical forms or routes of administration appear in the available records.
What do the clinical trials show?
One trial of leflutrozole is registered in the EU Clinical Trials Information System. The NOVA-NOA trial (2025-524774-42-00) is a Phase 2 interventional study in male infertility, specifically non-obstructive azoospermia. It is currently authorised, meaning it has received regulatory approval to proceed but has not yet reported results. The trial plans to enrol 15 participants.
The primary endpoint is the proportion of patients with spermatozoa in the ejaculate at Week 12–20. This measures whether treatment with leflutrozole leads to the appearance of sperm in semen where none were present before.
In addition, a separate Phase 2 study reported in the Journal of the Endocrine Society found a beneficial effect of leflutrozole on sperm production in men with obesity-associated secondary hypogonadotropic hypogonadism. In that study, the rationale was that excess aromatase activity in adipose tissue converts testosterone to estradiol, suppressing gonadotropins and reducing fertility.
What side effects are known?
The supplementary source provided does not describe specific side effects of leflutrozole. No side effect data are available from the trial registry record, which has not yet reported results.