Hydroxyurea Therapy Shown Not to Impact Onset of Puberty in Male Sickle Cell Disease Patients

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This new data on a European sickle cell disease cohort expands upon existing knowledge of the effects of HU on fertility, with the findings showing the benefits of cryopreservation.

Mariane De Montalembert, MD, PhD

Credit: Assistance Publique – Hôpitaux de Paris

Mariane De Montalembert, MD, PhD

Credit: Assistance Publique – Hôpitaux de Paris

Hydroxyurea (HU) therapy has no impact on the onset of puberty in male patients with sickle cell disease (SCD), according to new findings presented at the American Society of Hematology (ASH) 2023 meeting,

Prior to their research, the investigators of this study noted that male SCD patients have been known to face reproductive health issues, with some of these including pubertal delay that has been linked to SCD. Larger-scale studies on puberty onset in such people were also known to be scarce.

Fertility issues are common among males without HU therapy implementation, with below 10% exhibiting normal semen analysis results based on World Health Organization (WHO) guidelines. The investigators, led by Mariane De Montalembert, MD, PhD, added that HU treatment may exacerbate concerns about fertility for many.

“To address these concerns, various fertility preservation strategies have been developed for male SCD patients on HU, including sperm cryopreservation for pubescent boys and adults before starting HU, and temporary HU discontinuation when therapy is initiated in infancy for sperm banking, at best with monthly transfusion during the period without HU,” De Montalembert and colleagues wrote.

The European Sickle Cell Disease Cohort – Hydroxyurea Extension (ESCORT-HU Extension) study was a multicentric, prospective, non-interventional research initiative that the investigators carried out to look at the HU safety profile. They specifically looked into poorly-documented risks, such as ones related to puberty and fertility.

The research team’s work involved around 2000 HU-treated individuals over the course of a 5-year study period. Their research covered both subjects from the initial ESCORT-HU study and newer individuals that had to meet specific inclusion criteria.

A total of 1860 participants coming from Germany, France, Greece, and Italy, as of June 28, 2023, were included in the team’s research. Those enrolled, all of which showed a median age of 24, were 44.4% male.

The investigators also noted that around 87% had the HbSS genotype. Among the 455 pubescent male patients seen at enrollment, 72 were shown to have transitioned into puberty as the study took place with the median HU exposure duration being about 8.5 years.

Overall, the research team reported that there was no major difference in the mean age at Tanner V stage, related to onset of puberty, seen between the males who made it to puberty before and after their beginning HU therapy.

In terms of semen cryopreservation, among the 527 pubescent males, the team found that 49% began HU at or following 17 years old. In contrast to this, they reported that 234 started HU prior to turning 17, and 11% of them had cryopreservation, with participants’ median age at cryopreservation being 26.0 years.

Looking at the 104 semen analyses reported by the investigators, 66 were shown to be before HU initiation, with normal results in 78% and abnormal results in 22% of the subjects. Among 24 subjects following initiation of HU treatment, 11 were found to have temporarily discontinued their treatment, with varied results.

The research team added that 4 individuals ended up having both pre- and post-HU treatment semen analyses.

The investigators’ findings suggest that while some fertility data is pending, semen cryopreservation is observed to be widely embraced in Europe, with around 50% of those aged 17 and up opting for cost-free option of HU treatment in France.

“We confirm a significant proportion of semen abnormalities but not in all cases,” they wrote. “The impact of HU on fertility is complex, and cryopreservation appears to be beneficial in mitigating potential adverse effects, with at least one baby in our cohort born after use of cryopreserved semen.”

References

  1. De Montalembert M, Bartolucci P, De Luna G, et al. Puberty Onset and Preservation of Fertility in Male Patients with Sickle Cell Disease Treated with Hydroxyurea: Data from the European Sickle Cell Disease Cohort – Hydroxyurea Extension (ESCORT-HU Extension) Study. Presented at: ASH Annual Meeting and Exposition. San Diego, CA. December 9-12, 2023.
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