Combined contraceptive pills and immune system cells in the endometriotic cyst wall

New novel research of combined contraceptive pill effect on immune cells of endometriotic cyst walls

Key Points

Highlights: 

• Defective immunity is a frequently-mentioned operating factor among several others in endometriosis pathogenesis, as immune system dysregulation could yield a fertile soil for endometriosis initiation and development.
• Combined oral contraceptives are prescribed frequently since it is an estrogen-dependent disorder. 
• Very little information about the effects of combined oral contraceptives on immune cells of women with endometriosis has been on record.

What's done here: 

• Endometriotic cyst wall tissues were obtained during surgery both from women with endometriosis treated with combined oral contraceptives or untreated.
• These tissues were analyzed by immunohistochemistry, in terms of macrophages, natural killer cells, and regulatory T cells.

Key results:

• The endometriotic cyst walls of the group treated daily with a combined oral contraceptive (Ethinyl estradiol 0.30 mg, desogestrel 0.15 mg) showed a significant decrease in macrophage number.
• Also, a significantly higher number of natural killer cells and regulatory T cells were detected. 

Limitations of the study design:

• This is an observational study that might contain biases like patient selection, besides a relatively short period of hormonal therapy.
• Another study with a longer hormonal therapy span and conducted as a randomized control trial would be more reliable.

Lay Summary

Dr. Wanwisa Waiyaput and associates from Mahidol University, Bangkok, Thailand, have published their results on the immune regulatory cells of the surgically resected endometriotic cyst walls in the “Journal of Ovarian Research”.

The defective immune response is believed to have a major impact on the pathogenesis of endometriosis besides coelomic metaplasia, Mullerian rests, lymphatic and hematogenous spread, and differentiated stem cells, and “retrograde menstruation” theories.

Although the exact cause of endometriosis is unknown, it is an estrogen-dependent disorder making combined oral contraceptives a treatment choice. Combined oral contraceptives have been quite popular among other medications due to their high effectiveness along with low side effects, and low cost. There have been few documents concerning combined oral contraceptives on the immune cells of women with endometriosis. 

This research aimed to investigate the effect of oral contraceptives on immune cells of endometriotic tissues. Most previous studies concerning immune cells investigated peritoneal fluid and peripheral blood, but the present study directly investigated immune cells in endometriotic cyst walls. Surgically removed endometriotic cyst walls from women with endometriosis treated (n = 22) with combined oral contraceptives (one pill per day of Ethinyl estradiol 0.03 mg and desogestrel 0.15 mg administered for 28 to 35 days preoperatively) or untreated (n = 22). Immunohistochemistry for markers of macrophages, natural killer cells, and regulatory T cells was utilized.

The median number of anti-CD68 positive macrophages in the oral contraceptive taking group was significantly lower than in the untreated group. Anti-CD56 positive natural killer cells were significantly higher in the treatment group compared with tissue from the untreated group. The number of regulatory T cells marked by anti-FoxP3 was also significantly increased in the oral contraceptive pill group.

These findings in patients on combined oral contraceptive, containing Ethinyl estradiol 0.30 mg with desogestrel 0.15 mg, affected the immune system resulting in a significant decrease in the number of macrophages and an increase in natural killer and regulatory T cells provides valuable evidence as a supportive clue for the dysregulated immunity in endometriosis pathogenesis.

Research Source: https://pubmed.ncbi.nlm.nih.gov/33980258/