Comprehensive Systematic Review of long-term opioids in women with chronic non cancer pain and associated reproductive dysfunction (hypothalamic-pituitary-gonadal axis disruption).
Emily Wersocki, John Bedson, Ying Chen, Linda LeResche, Kate M Dunn, .
A comprehensive systematic literature review of reproductive side effects in women 18-55 years old treated with opioids for one month or longer for chronic non cancer pain. A search of seven databases including EMBASE and Medline was undertaken (October 2014 and a limited re-run April 2016). The search contained key words for opioids (generic and specific drug names) and side effects (generic and specific reproductive). Titles were screened using predefined criteria by a single reviewer and abstracts and full texts by two independent reviewers. 10,684 papers were identified and 12 full texts (cohort (one), case-control (four), cross-sectional (four), case series (one) and case report (two) with a maximum of 41 cases in one paper) were included covering three different modes of administration: oral (six), intrathecal (five) and transdermal (one). Amenorrhoea occurred in 23-71% of those receiving oral or intrathecal opioids. Decreased libido was seen in 61-100%. Out of 10 studies which undertook hormonal assays, only two studies showed a statistically significant decrease in hormone levels. This review supports the view that there is a potential relationship between the use of long-term opioids in women and reproductive side effects. The evidence is however weak and the mode of administration, duration, type and dose of opioid might influence associations. Though hormone levels were statistically significant in only two studies, women exhibited clinically important symptoms (decreased libido and altered menstrual cycle). Further investigation is required with larger cohorts and analysis of different delivery methods.