Overuse of analgesics can affect the fertility biomarker Anti-Müllerian Hormone in females. A translational study

• Published in: Cephalalgia 2024-11, Vol.44 (11), p.3331024241290530
• Main Authors: Carlsen, Louise Ninett, Nielsen, Brian Skriver, Rouw, Carolien, Petersen, Morten Rønn, Lindh, Christian H, Krais, Annette M, Westgate, Connar Stanley James, Jeppesen, Janni Vikkelsø, Jensen, Lea Bejstrup, Kristensen, Stine Gry, Ziebe, Søren, Jensen, Rigmor Højland, Kristensen, David Møbjerg
• Format: Article
• Language: English
• Subjects: Adult; Analgesics; Anti-Mullerian Hormone - blood; Biomarkers - blood; Female; Fertility - drug effects; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Headache Disorders, Secondary; Humans; Prospective Studies; Translational Research, Biomedical; Young Adult
• ISSN: 0333-1024; 1468-2982; 1468-2982
• DOI: 10.1177/03331024241290530

Background Medication overuse headache is a prevalent secondary headache due to the overuse of analgesics, mainly over-the-counter analgesics. Over-the-counter analgesics have been associated with disrupted male endocrinology, while the effects on female endocrinology remain nearly unknown. The aim was to understand the effect of long-term analgesic exposure in females with medication overuse headache on Anti-Müllerian hormone, a surrogate measure of female fertility. Methods Using a translational approach, an observational prospective clinical study was conducted to determine the effect of withdrawal therapy in females with medication overuse headache on Anti-Müllerian hormone levels, in combination with pre-clinical investigation of primary granulosa cells to understand the effects of analgesics on granulosa cell function. Results We included 21 females (mean-age 30.0 years; SD (7.3)) for Anti-Müllerian hormone -measurement. Anti-Müllerian Hormone increased by 21% from baseline (mean 20.1 pmol/L; SD (8.7)) after withdrawal of analgesics ((mean 24.3 pmol/L; SD (12.0)); p = 0.0023). Exposing primary granulosa cells to analgesics (acetaminophen (100 and 200 µM, n = 9–10) and ibuprofen (150 and 200 µM, n = 12–13)) did not reduce Anti-Müllerian hormone levels. In contrast, de novo DNA synthesis in GCs (n = 6) exposed to acetaminophen was reduced by 78% (p = 0.0036) compared to controls, suggesting that cellular proliferation was restricted. Conclusion We found that frequent use of over-the-counter analgesics was associated with repressed Anti-Müllerian Hormone levels, likely through disruption of granulosa cell proliferation. Further research is crucial to investigate a potential effect of analgesics on adult female reproductive endocrinology. Trial registration: ClinicalTrials.gov Identifier NCT04090333 Graphical abstract This is a visual representation of the abstract.