Increased risk of reproductive dysfunction in women prescribed long-term opioids for musculoskeletal pain: A matched cohort study in the Clinical Practice Research Datalink.

BACKGROUND: One-fifth of primary care attendees suffer chronic noncancer pain, with musculoskeletal conditions the leading cause. Twelve percent of patients with chronic noncancer pain are prescribed strong opioids. Evidence suggests long-term opioid use is related to hypogonadism in men, but the relationship in women is unclear. Our aim was to investigate reproductive dysfunction in women prescribed long-term opioids for musculoskeletal pain.

METHODS: We undertook a matched (matched 1:1; for year of birth, year of start of follow-up and practice) cohort study of women aged 18-55 years old, with musculoskeletal pain and an opioid prescription in the Clinical Practice Research Datalink (a primary care database) between 2002 and 2013. Long-term opioid users (≥90 days) were compared with short-term opioid users (<90 days) for four reproductive conditions (abnormal menstruation, low libido, infertility and menopause) using Cox proportional hazards models.

RESULTS: A total of 44,260 women were included; the median cohort age at baseline was 43 years (Interquartile Range 36-49). Long-term opioid use was associated with an increased risk of altered menstruation (hazard ratio 1.13 95% CI 1.05-1.21) and with an increased risk of menopause (hazard ratio 1.16 95% CI 1.10-1.23). No significant association was found for libido (hazard ratio 1.19 95% CI 0.96-1.48) or infertility (hazard ratio 0.82 95% CI 0.64-1.06).

CONCLUSIONS: The risk of menopause and abnormal menstruation was increased in long-term opioid users. This has implications for clinicians as reproductive dysfunction will need to be considered when prescribing long-term opioids to women with musculoskeletal conditions.

SIGNIFICANCE: This is a large-scale cohort examining the relationship between long-term opioid use and reproductive dysfunction using a UK national primary care database. There is an increased risk of reproductive dysfunction associated with long-term opioid use.