O-134 Cochrane review on the effect of pentoxifylline for endometriosis
Authors: Grammatis A , Georgiou E X , Becker C M 
Published: August 2021

Abstract

Study question
To assess the effect of pentoxifylline, a methyl-xanthine with anti-inflammatory effects, for the management of premenopausal women with endometriosis.

Summary answer
There is not enough evidence to support the use of pentoxifylline in the management of premenopausal women with endometriosis to improve fertility and pain outcomes.

What is known already
Endometriosis is a chronic, inflammatory condition that occurs mainly during the reproductive years. It is characterized by endometrium-like tissue developing outside the uterine cavity. This endometriotic tissue development is dependent on estrogen produced primarily by the ovaries and partially by the endometriotic tissue itself and, therefore, hormonal management is traditionally used. In light of the body of evidence suggesting an immunological component to the pathophysiology of endometriosis, the anti-inflammatory agent pentoxifylline has been proposed as an alternative therapeutic agent.

Study design, size, duration
A Cochrane systematic review and meta analysis was performed. Electronic searches of the Cochrane Gynaecology and Fertility Specialised Register of Controlled Searches, CENTRAL, MEDLINE, EMBASE, PsycINFO, CINAHL and AMED OVID were conducted to December 2020 to identify relevant randomised controlled trials (RCTs). In addition, electronic searches were conducted on the Epistemonikos database, Human Reproduction, Web of Knowedlge, OpenGrey, LILACS, Pubmed and Google.

Participants/materials, setting, methods
Participants: premenopausal women with endometriosis via laparoscopy/laparotomy. For extent of endometriosis, grades according to the AFS/rASRM scoring system were used.
Intervention: pentoxifylline treatment for any period of time
Comparisons: placebo, no treatment, medical treatment, surgical treatment.
Two independent authors screened studies and extracted data. Risk ratios were calculated for dichotomous data (Peto odds ratio for low event rates) and mean differences (MD) for continuous data, with 95% confidence intervals (CI).

Main results and the role of chance
Five RCTs were included, involving 415 participants.

Pentoxifylline vs placebo
No trials reported on live birth or reduction of pain. We are uncertain whether pentoxifylline affects the clinical pregnancy rate (Peto OR 1.53, 95% CI 0.89 to 2.63; 3 RCTs, n = 285; I2 = 0%; very low-quality evidence), recurrence rate (Peto OR 0.83, 95% CI 0.26 to 2.60; 1 RCT, n = 121; very low-quality evidence), or miscarriage rate (Peto OR 1.99, 95% CI 0.20 to 19.37; 2 RCTs, n = 164; I2= 0%; very low-quality evidence).

Pentoxifylline vs no treatment
We are uncertain whether pentoxifylline impacts on pain reduction when compared to no treatment at one month (MD -0.36, 95% CI -2.08 to 1.36; 1 RCT; n = 34; very low-quality evidence), two months (MD -1.25, 95% CI -2.67 to 0.17; 1 RCT; n = 34; very low-quality evidence) or three months (MD -1.60; 95% CI -3.32 to 0.12; n = 34; very low-quality evidence). No studies reported on live birth.

Pentoxifylline vs medical treatment
One study compared pentoxifylline with the combined contraceptive pill, but could not be included in the meta-analysis, as it was unclear if the data were presented as +/- standard deviation.

Pentoxifylline vs surgical treatment
No study reported on this comparison

Limitations, reasons for caution
Based on the GRADE criteria, the quality of evidence was classified as very low with issues arising due to risk of bias and imprecision. Four studies did not apply the intention-to-treat principle. None of the studies reported on live birth rate, one of the primary outcomes of the review.

Wider implications of the findings
Future research should prioritise live birth and overall pain as the primary outcome and include patients with all endometriosis severity types. All included studies compared pentoxifylline with placebo or no treatment after surgery, which highlights the need for more types of comparisons, such as to hormonal contraception.

Trial registration number
Not applicable