Proposal for targeted, neo-evolutionary-oriented secondary prevention of early-onset endometriosis and adenomyosis. Part II: medical interventions

Abstract

According to consistent epidemiological data, the slope of the incidence curve of endometriosis rises rapidly and sharply around the age of 25 years. The delay in diagnosis is generally reported to be between 5 and 8 years in adult women, but it appears to be over 10 years in adolescents. If this is true, the actual onset of endometriosis in many young women would be chronologically placed in the early postmenarchal years. Ovulation and menstruation are inflammatory events that, when occurring repeatedly for years, may theoretically favour the early development of endometriosis and adenomyosis. Moreover, repeated acute dysmenorrhoea episodes after menarche may not only be an indicator of ensuing endometriosis or adenomyosis, but may also promote the transition from acute to chronic pelvic pain through central sensitization mechanisms, as well as the onset of chronic overlapping pain conditions. Therefore, secondary prevention aimed at reducing suffering, limiting lesion progression, and preserving future reproductive potential should be focused on the age group that could benefit most from the intervention, i.e. severely symptomatic adolescents. Early-onset endometriosis and adenomyosis should be promptly suspected even when physical and ultrasound findings are negative, and long-term ovulatory suppression may be established until conception seeking. As nowadays this could mean using hormonal therapies for several years, drug safety evaluation is crucial. In adolescents without recognized major contraindications to oestrogens, the use of very low-dose combined oral contraceptives is associated with a marginal increase in the individual absolute risk of thromboembolic events. Oral contraceptives containing oestradiol instead of ethinyl oestradiol may further limit such risk. Oral, subcutaneous, and intramuscular progestogens do not increase the thromboembolic risk, but may interfere with attainment of peak bone mass in young women. Levonorgestrel-releasing intra-uterine devices may be a safe alternative for adolescents, as amenorrhoea is frequently induced without suppression of the ovarian activity. With regard to oncological risk, the net effect of long-term oestrogen-progestogen combinations use is a small reduction in overall cancer risk. Whether surgery should be considered the first-line approach in young women with chronic pelvic pain symptoms seems questionable. Especially when large endometriomas or infiltrating lesions are not detected at pelvic imaging, laparoscopy should be reserved to adolescents who refuse hormonal treatments or in whom first-line medications are not effective, not tolerated, or contraindicated. Diagnostic and therapeutic algorithms, including self-reported outcome measures, for young individuals with a clinical suspicion of early-onset endometriosis or adenomyosis are proposed.

Keywords: adenomyosis; central sensitization; chronic pelvic pain; endometriosis; laparoscopy; menstruation; oral contraceptives; ovulation; progestogens.

Figure 1.

Proposal for a diagnostic and therapeutic algorithm, including self-reported outcome measures, for the young menstruator with severe dysmenorrhoea, chronic, acyclic pelvic pain symptoms, and a clinical suspicion of early-onset endometriosis who prefers medical suppression of menses to surgery, and accepts, tolerates, and has no contraindications to long-term hormonal treatment. US, ultrasonographic scan; MRI, magnetic resonance imaging; LNG-IUS, levonorgestrel-releasing intra-uterine system; PGIC, patient global impression of change 7-point scale (Guy, 1976; Dworkin et al., 2005); CPP, chronic pelvic pain. *After at least 3-month treatment. ^†Based on data from Vercellini et al. (2023a). ^‡Central Sensitization Inventory 0–100 score (Mayer et al., 2012; Orr et al., 2022, 2023b; Cetera et al., 2023a). ^§Based on data from Neblett et al. (2017) and Orr et al. (2020, 2023b).

Figure 2.

Proposal for a diagnostic and therapeutic algorithm, including self-reported outcome measures, for the young menstruator with heavy menstrual bleeding, severe dysmenorrhoea, and a clinical suspicion of early-onset adenomyosis who accepts, tolerates, and has no contraindications to long-term hormonal menstrual suppression. US, ultrasonographic scan; MRI, magnetic resonance imaging; LNG-IUS, levonorgestrel-releasing intra-uterine system; PGIC, patient global impression of change seven-point scale (Guy, 1976; Dworkin et al., 2005). *After at least 3-month treatment.