Hormonal birth control may raise diabetes risk for some CF women
Study suggests that use of CFTR modulators could be a protective factor
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The use of combined hormonal contraceptives by women with cystic fibrosis (CF) who are not taking CFTR modulators increases by 53% the risk of developing CF-related diabetes (CFRD), a study in the U.S. found.
Conversely, combined hormonal contraceptive “use was not associated with increased CFRD incidence among modulator users, suggesting that modulator use may be protective among [combined hormonal contraceptive] users,” the scientists wrote.
The study, “Association of CFRD development among females with CF who use hormonal contraception,” was published in the Journal of Cystic Fibrosis.
About half of adults with CF develop CF-related diabetes
CF is caused by genetic mutations that result in the loss or dysfunction of the CFTR protein, leading to the accumulation of thick, sticky mucus in various organs. The disease symptoms particularly affect the respiratory, digestive, and reproductive systems.
About half of adults with CF develop CFRD, a condition in which blood glucose (blood sugar) is too high. CFRD develops due to mucus accumulation in the pancreas, resulting in insufficient production of insulin, a hormone that helps move glucose from blood into cells, and impaired response to insulin.
Due to treatment advances, most CF patients are now adults, and reproductive planning has become a new priority, with studies showing that almost all women with CF have used at least one type of contraceptive. However, the use of combined hormonal contraceptives, containing estrogen and progestin (a synthetic version of progesterone), can affect insulin response.
CFRD risk affected by whether women used CFTR modulators
In this study, the researchers aimed to understand whether the use of hormonal contraceptives increases the risk of developing CFRD. The study enrolled 551 women with CF from 10 CF centers who completed an online survey about contraceptive use between 2008 and 2020. Survey responses were linked to the CF Foundation’s Patient Registry in the same period.
Based on registry records, 88 women (16%) had CFRD at the first year (baseline), and 145 (26.3%) developed the condition during a median follow-up of 10 years. This corresponded to 3.9 new cases per 100 person-years, meaning that on average, there were about 3.9 new CFRD cases per 100 people followed for one year.
When available, hemoglobin A1C, fasting blood glucose, and the 2-hour oral glucose tolerance test, all of which assess blood sugar levels, were significantly associated with CFRD. Neither age nor body mass index (BMI), a measure of body fat based on height and weight, was associated with CFRD.
[Findings showed that combined hormonal contraceptive] use is associated with increased risk for CFRD among non-modulator users, even after accounting for [body mass index], age, and other risk factors.
The risk of developing CFRD was affected by whether women used CFTR modulators. Among those who were not treated with these drugs, use of combined hormonal contraceptives was associated with a 53% higher likelihood of having CFRD. In contrast, the risk was not higher among women who took progestin-only contraceptives or in those treated with modulators.
Results also showed a lower CFRD risk (by 36%) among women with higher education level.
Further analysis expanded the CFRD definition to include women with any blood glucose measure above the diagnostic threshold, including hemoglobin A1c greater than 6.5%, fasting glucose greater than 126 mg/dL, and a two-hour glucose greater than 200 mg/dL after a glucose tolerance test. Results here further supported the higher CFRD risk among non-modulator users taking combined hormonal contraceptives.
Taken together, the findings showed that combined hormonal contraceptive “use is associated with increased risk for CFRD among non-modulator users, even after accounting for [body mass index], age, and other risk factors,” the researchers wrote. They “further confirm that [progestin-only contraceptives] have no significant association with glycemic control in the CF population, regardless of modulator use.”
