Sex Hormone Levels Significantly Affect Treatment-Free Survival in Chronic Lymphocytic Leukemia

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Men have approximately double the incidence rate, are more likely to have progressive and treatment-resistant disease, and have a poorer prognosis compared with women with CLL.
Men have approximately double the incidence rate, are more likely to have progressive and treatment-resistant disease, and have a poorer prognosis compared with women with CLL.

Levels of various circulating sex hormones may significantly affect treatment-free survival (TFS) among male and female patients with chronic lymphocytic leukemia (CLL), according to a study published in Annals of Hematology.1

Although CLL is not characterized as a hormone-regulated disease, sex is a recognized risk factor; men have approximately double the incidence rate, are more likely to have progressive and treatment-resistant disease, and have a poorer prognosis compared with women.

In this study, researchers assessed the outcomes of 61 female and 95 male patients with CLL, and 10 healthy donors. Twenty-nine circulating steroid levels were quantified using mass spectrometry, including adrenal precursors, androgens, catechol estrogens, estrogens, and progesterone. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels were measured as well. Patient characteristics, such as age, cytogenetic aberrations, and treatment-free survival, were evaluated.

After a median follow-up of 12.75 years, results showed that men had a significantly shorter median TFS of 80.7 months compared with 135.0 months among women (P = .033).

Patients with CLL had significantly different circulating hormone profiles compared with the healthy donors; among males with CLL, high levels of LH was significantly associated with a shorter TFS (adjusted hazard ratio [HRadj], 2.11; P = .004). Among female patients, improved TFS was significantly associated with high levels of testosterone (HRadj, 0.24; P = .007), dihydrotestosterone (HRadj, 0.54; P = .023), and total methoxy-estrogens (HRadj, 0.31; P = .034).

Women with CLL characterized by a high expression of UGT2B17 — an enzyme known to inactivate steroids — had a shortened TFS.

The authors concluded that “larger studies will need to be conducted to replicate our initial observations and to assess potential changes in hormone levels during the evolution of the disease and how drug treatment potentially affects their relationship with disease progression, both in men and women.”

Reference

  1. Allain EP, Venzl K, Caron P, et al. Sex-dependent association of circulating sex steroids and pituitary hormones with treatment-free survival in chronic lymphocytic leukemia patients [published online May 21, 2018]. Ann Hematol. doi: 10.1007/s00277-018-3356-z

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