The efficacy of progestins in managing pain associated with endometriosis, fibroids and pre-menstrual syndrome: a systematic review.

Purpose: Alongside being contraceptives, progestins have been investigated as potential anti-inflammatory and analgesic therapies for use in painful gynaecological conditions. This review aims to synthesise evidence pertaining to the efficacy of progestins as analgesics for use in endometriosis, fibroids and pre-menstrual syndrome (PMS).

Methods: We conducted a systematic review of the extant literature investigating the analgesic efficacy of progestins compared to any comparator interventions for individuals with the three specified gynaecological conditions. The search was carried out across the PubMed and CENTRAL databases on 7 April 2024 for randomised control trials (RCTs) published in the peer-reviewed literature from 2000 onwards. Data pertaining to analgesic efficacy, assessed by changes in pain indices/scores before and after treatment, were synthesised narratively. Data pertaining to adverse effect frequency and changes in bone mineral density (BMD) were also synthesised narratively. Risk of bias was assessed using the Cochrane risk of bias 2 tool.

Results: The primary search identified 1220 potentially eligible RCTs of which 21 were ultimately included; 19 RCTs related to endometriosis, two related to fibroids and zero related to PMS. Quality assessment identified nine studies to be at a low risk of bias, nine studies with some concerns surrounding bias and three studies to be at a high risk of bias. The included studies represented a total of 2745 participants of whom 1317 were treated with a progestin and 1428 received a comparator intervention. In 18 of the 19 studies concerning endometriosis, progestins produced a statistically significant reduction in pain, further, in five instances progestins were more efficacious in reducing pain than comparator interventions. In both studies on fibroids, progestins produced significant reductions in pain, however, statistically significant differences compared to comparator interventions were not demonstrated. The most frequently cited adverse effect of progestins was spotting/irregular bleeding whilst those receiving comparator interventions most often reported hot flushes; cited in 12 and seven studies respectively. Five studies assessed the impact of progestins and comparators on BMD. Three studies found progestins significantly reduced BMD, however, in these instances reductions were significantly lower than those produced by comparator interventions and in two studies were not statistically significant after 12 months of follow-up.

Conclusion: Our review demonstrates the potential scope for the use of progestins as analgesics in the management of pain associated with endometriosis. Further research will need to be conducted to identify their efficacy in the management of pain associated with fibroids and PMS.