Update on Medical Treatment of Endometriosis: New Drugs or New Therapeutic Approaches?

BACKGROUND: No conceptually new drugs for the safe and successful cure of endometriosis are likely to become available soon. Hormonal modulation of ovarian function and suppression of menstruation remain the pillars of disease control. However, existing drugs may be used following novel modalities to limit the consequences of endometriosis progression. OBJECTIVES: The aims of this review were to propose a pharmacological approach aimed at limiting the potential detrimental effects of the recent dramatic increase in postmenarcheal repetitive ovulatory menses and to define the type of hormones and the routes of administration that can be used to maximize safety and tolerability in the medical treatment of endometriosis. METHODS: For this narrative review, we selected the best quality evidence, prioritizing RCTs, systematic reviews, meta-analyses, network meta-analyses, and international guidelines, preferably published in the last decade. OUTCOME: Medical treatment of endometriosis should be included into all aspects of prevention. Very-low-dose combined oral contraceptives can be used for years to counteract the increased risk of ovarian cancer observed in patients with endometriosis. This primary prevention measure saves lives and can effectively integrate targeted risk-reducing surgery. Secondary pharmacological prevention, based on a working diagnosis of early onset adenomyosis-endometriosis selectively in adolescents with severe dysmenorrhea and heavy menstrual bleeding, can potentially impede the development of advanced disease forms, and reduce the need for management of complications due to a delay in diagnosis and treatment. Tertiary prevention, i.e., medical therapy of established disease, is based initially on the safest available estrogen-progestogen combinations and progestogen monotherapies. Whenever possible, ethinyl estradiol and cyproterone acetate should be avoided because of thromboembolic and meningioma risks, respectively. Estradiol can be administered transdermally. Switching to gonadotropin-releasing hormone agonists and antagonists should not be delayed when the first-line agents fail. CONCLUSIONS AND OUTLOOK: Two-thirds of symptomatic endometriosis patients can be managed satisfactorily for many years using, with the right modality, the existing safe, effective, and well-tolerated medications. Despite the constant plea for new drugs, this already appears to be an excellent clinical outcome, unsurpassed when managing other human chronic inflammatory diseases. Cohort studies are needed to verify whether turning off the recurrent inflammation caused by repeated ovulation and menstruation could also affect the risk of systemic conditions associated with endometriosis.