Abstract
Background/ObjectiveVascular endothelial growth factor (VEGF) is the most important promotor of angiogenesis. Some studies indicate that anti-angiogenic agents that interfere with VEGF and its receptor (VEGFR), i.e., anti-VEGF/VEGFR agents, may be applied to treat endometriosis. This meta-analysis investigated the efficacy of anti-VEGF/VEGFR agents in animal models of endometriosis.MethodsA systematic literature search was performed for animal studies published in English or Chinese from January 1995 to June 2016, which evaluated the effect of anti-VEGF/VEGFR agents on endometriosis. The databases were: PubMed, Web of Science, BIOSIS, Embase, and CNKI. The quality of included studies was assessed using the SYRCLE tool. The random-effect models were used to combine the results of selected studies. Heterogeneity was assessed using H2statistic and I2 statistic. Subgroup analyses were performed to determine the source of heterogeneity in endometriosis scores and follicle numbers.ResultsWe identified 13 studies that used anti-VEGF/VEGFR agents in various animal models. The meta-analysis showed that anti-VEGF/VEGFR agents were associated with smaller size (standardized mean difference (SMD) –0.96, 95% CI –1.31 to –0.62; P < 0.0001) and weight (SMD –1.70, 95% CI –2.75 to –0.65; P = 0.002) of endometriosis lesions, relative to the untreated controls, as well as a lower incidence rate of endometriosis (risk ratio 0.26, 95% CI 0.07 to 0.93; P = 0.038) and endometriosis score (SMD –1.17, 95% CI –1.65 to –0.69; P < 0.0001); the number of follicles were similar (SMD –0.78, 95% CI –1.65 to 0.09; P = 0.08).ConclusionsAnti-VEGF/VEGFR agents appeared to inhibit the growth of endometriosis, with no effect on ovarian function. Anti-angiogenic therapy may be a novel strategy in treating endometriosis.
Highlights
Endometriosis is a common benign disease in women of reproductive age
We identified 13 studies that used anti-Vascular endothelial growth factor (VEGF)/VEGF and its receptor (VEGFR) agents in various animal models
The meta-analysis showed that anti-VEGF/VEGFR agents were associated with smaller size (standardized mean difference (SMD) –0.96, 95% confidence intervals (CIs) –1.31 to –0.62; P < 0.0001) and weight (SMD –1.70, 95% CI –2.75 to –0.65; P = 0.002) of endometriosis lesions, relative to the untreated controls, as well as a lower incidence rate of endometriosis and endometriosis score (SMD –1.17, 95% CI –1.65 to –0.69; P < 0.0001); the number of follicles were similar (SMD –0.78, 95% CI –1.65 to 0.09; P = 0.08)
Summary
Endometriosis is a common benign disease in women of reproductive age. The pathogenesis of endometriosis is not completely understood, but rates of recurrence at 2 and 5 years are ~21.5% and 40~50%, respectively [1]. Chronic pelvic pain and infertility are very common [2, 3], which markedly affect patients’ quality of life and increase the economic burden of the health-care system [4]. The current treatment of endometriosis involves surgical removal of the endometriotic lesions and pharmacological therapy. Pharmacological therapy mainly refers to suppression of endogenous estrogen synthesis with oral contraceptives, gonadotropin-releasing hormone (GnRH) agonists, aromatase inhibitors, and androgenic agents. The disease may recur after surgical excision, or after drug withdrawal, and the substantial side effects associated with this class of drugs limit their long-term use. Reliable new modalities for the long-term treatment of endometriosis are required
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