Medical Treatment for Endometriosis: One Size Does Not Fit All

Endometriosis is associated with nociceptive pain and with peripheral as well as central sensitization. To relieve nociceptive pain, most symptomatic patients benefits from hormonal therapy, which includes first-line (progestogens and estrogen-progestogen combinations) and second-line (GnRH agonists and antagonists) medications. To reduce venous and arterial thrombotic risk and avoid lesion stimulation, combinations containing bioidentical estrogens should be preferred to those containing ethinyl-estradiol. Irregular bleeding is the main adverse effect of first-line medications, adversely impacting efficacy, tolerability, and adherence. When progestogens and estrogen-progestogens do not improve the quality of life, prompt stepping up to GnRH analogues combined with add-back therapy is indicated. An add-on rather than upfront combination therapy is suggested. Keeping analogues and add-back therapy separate allows for the choice of the compounds that best suit individual patients’ characteristics. The transdermal use of bioidentical estradiol is suggested in combination with both progestogens and GnRH analogues. Similar satisfactory outcomes are achieved with GnRH agonists and antagonists. The evidence on neuromodulatory drugs to treat neuropathic and nociplastic pain is derived from other chronic pain conditions, and it demonstrates a limited effect. The two mainstays of hormonal therapy are i) ovariostasis and ii) amenorrhea. Whenever these are not obtained, and a shift from first-line to second-line medications has not been undertaken, “medical treatment failure” must not be declared. In severely symptomatic adolescents and young women, secondary prevention via ovariostasis and amenorrhea should be promptly pursued to improve quality of life, halt lesion progression, and preserve the reproductive potential.