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

Carlsen, Louise Ninett ; Nielsen, Brian Skriver ; Rouw, Carolien ; Petersen, Morten Rønn ; Lindh, Christian H. LU orcid ; Krais, Annette M. LU orcid ; Westgate, Connar Stanley James ; Jeppesen, Janni Vikkelsø ; Jensen, Lea Bejstrup and Kristensen, Stine Gry , et al. (2024) In Cephalalgia 44(11).
Abstract

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... (More)

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

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
acetaminophen/paracetamol, Anti-Müllerian hormone, medication overuse headache, non-steroidal anti-inflammatory drugs, simple analgesics
in
Cephalalgia
volume
44
issue
11
publisher
SAGE Publications
external identifiers
  • scopus:85210047570
  • pmid:39558601
ISSN
0333-1024
DOI
10.1177/03331024241290530
language
English
LU publication?
yes
additional info
Publisher Copyright: © International Headache Society 2024.
id
2248ab58-db02-47fe-b77f-89c53c1982b8
date added to LUP
2025-01-14 15:14:01
date last changed
2025-07-16 06:10:31
@article{2248ab58-db02-47fe-b77f-89c53c1982b8,
  abstract     = {{<p>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</p>}},
  author       = {{Carlsen, Louise Ninett and Nielsen, Brian Skriver and Rouw, Carolien and Petersen, Morten Rønn and Lindh, Christian H. and Krais, Annette M. and Westgate, Connar Stanley James and Jeppesen, Janni Vikkelsø and Jensen, Lea Bejstrup and Kristensen, Stine Gry and Ziebe, Søren and Jensen, Rigmor Højland and Kristensen, David Møbjerg}},
  issn         = {{0333-1024}},
  keywords     = {{acetaminophen/paracetamol; Anti-Müllerian hormone; medication overuse headache; non-steroidal anti-inflammatory drugs; simple analgesics}},
  language     = {{eng}},
  number       = {{11}},
  publisher    = {{SAGE Publications}},
  series       = {{Cephalalgia}},
  title        = {{Overuse of analgesics can affect the fertility biomarker Anti-Müllerian Hormone in females. A translational study}},
  url          = {{http://dx.doi.org/10.1177/03331024241290530}},
  doi          = {{10.1177/03331024241290530}},
  volume       = {{44}},
  year         = {{2024}},
}