Abhishek Mahajan (narrator / author)

All 16 of the male endometriosis patients likely had increased estrogen levels, either due to liver cirrhosis, which leads to a decreased ability to break down estrogen, high-dose estrogen therapy for prostate cancer or obesity.

You may instinctively wonder, does endometriosis also occur in transgender women on hormone replacement therapy?

Unfortunately, I was unable to find any evidence of this, but I chalk it up to the relatively small number of people in this demographic having a similarly rare condition.

So what does cause endometriosis?

Well, we'll need a theory that deals with multiple issues at once.

1.

Accounts for endometriosis occurring in regions far from the pelvic region.

A rules out retrograde menstruation hypothesis.

2.

Accounts for endometriosis being a very heritable disease.

A rules out purely environmental explanations, for example greater air pollution, microplastics, etc.

3.

Accounts for endometriosis occurring, albeit very rarely, in non-menstruating individuals.

A rules out any theory that requires the endometrial lining to exist at all.

It's a tough set of criteria.

And a lot of theories have spawned to explain it.

There's the embryonic rest theory, which blames the condition on pockets of endometrial cells that never migrated properly during embryogenesis and instead remain dormant in various tissues, only to be activated later by hormones like estrogen.

This explains the disease occurring in cisgender men, as everyone starts off with progenitor cells capable of differentiation into endometrial cells, and cisgender women who theoretically should lack a shedding endometrial layer.

But, unfortunately, it fails to account for why 90% of all clinically visible endometriosis lesions still cluster on the pelvic region's ovaries rather than turning up at random sites, and why onset tracks so tightly with the start of the menstrual cycle and mysteriously improves during pregnancy.

A cousin to this is the salomic metaplasia theory, which asserts that the salomic epithelium, the layer of cells that lines the surfaces of all abdominal organs, retains the plasticity to transform into endometrial-like tissue under specific stimuli, such as hormonal signals, inflammation, or genetic predisposition.