Oncological outcomes in post-menopausal women with Kallmann syndrome: A propensity-matched study from the Global Federated Health Network.

Abstract

e23061 Background: Kallmann syndrome, a rare form of hypogonadotropic hypogonadism with anosmia, is a condition primarily seen and understood in males. Little information is available regarding the smaller subset of females with the condition. The current standard of care for management of Kallmann syndrome includes hormone-replacement therapy (HRT) that includes estrogen and progesterone, to mimic hormonal profiles of females without the condition. Though estrogen and its metabolites have been implicated in multiple malignancies, little is known about the impact of HRT on post-menopausal women with Kallmann syndrome. Methods: To investigate rates of estrogen-associated malignancies in post-menopausal females with Kallmann syndrome, TriNetX’s US Collaborative Network was used to query deidentified health information. Females with Kallmann syndrome at or over 50 years old were stratified into those prescribed and not prescribed HRT. Those on HRT were compared with women at or over 50 years old without Kallmann syndrome on HRT. Those with Kallmann syndrome not on HRT were compared with women at or over 50 years old without Kallmann syndrome not on HRT. Kallmann syndrome cohorts were then compared with each other. Rates of development of breast, endometrial, ovarian, and colorectal cancer were studied, as well as non-small cell lung cancer (NSCLC). Results: Propensity-score matching identified 10,506 patients per cohort with Kallmann syndrome both with and without HRT. Between cohorts, there were no significant differences in rates of breast, endometrial, ovarian, colorectal cancers, or NSCLC. Propensity-score matching between females with Kallmann syndrome on HRT at or over 50 years old and females at or over 50 years old without Kallmann syndrome and with HRT identified 10,065 patients per cohort. There was a significantly higher rate in the Kallmann cohort of endometrial cancer (HR 1.236, 95% CI 0.832-1.837, p=0.009). Propensity-score matching between females with Kallmann syndrome without HRT at or over 50 years old and females at or over 50 years old without Kallmann syndrome and without HRT found 45,736 patients per cohort. In the cohort without Kallmann syndrome, there was a significantly higher risk of endometrial cancer (HR 2.876, 95% CI 2.465-3.355, p=0.000), NSCLC (HR 1.08, 95% CI 0.816-1.429, p=0.046), and colorectal cancer (HR 1.02, 95% CI 0.865-1.202, p=0.008). Conclusions: Our findings indicate that HRT does not appear to affect estrogen-associated cancer risk among post-menopausal women with Kallmann syndrome. There may be differences between cancer rates that are related to the syndrome itself, as evidenced by differences between Kallmann cohorts and non-Kallmann cohorts. Further research should focus on exploring these differences.