1
Natural history: Basics of endometriosis
Arshi Syal and Seema Chopra
Ancient descriptions suggesting the diagnosis of endometriosis
Ovarian endometriosis
Identification of adenomyoma
Adenomyosis and endometriosisâThe differentiation
References
Endometriosis is a relatively common and potentially debilitating condition affecting women of reproductive age. Symptomatic endometriosis can result in long-term adverse effects on personal relationships, quality of life, and work productivity. As there is no clarity regarding the etiopathogenesis to date, researchers have shown a keen interest in the history of endometriosis over the past few decades.
Although, medical texts older than 4000 years have described this entity [1], Karl von Rokitansky was the first to diagnose endometriosis microscopically in 1860 [2].
As long as 2500 years ago, the disease with symptomatology of chronic pelvic pain was treated as a true organic disorder. As it was difficult to differentiate the menstrual pain from the severe pain due to endometriosis, during the middle ages, there was a shift from organic cause into the belief that women with pelvic pain were malingering or immoral, had female weakness, or were misbehaving. There was development of an attitude of indifference to the patientsâ true pain. Hence, through the ages, the historical diagnosis of hysteria in women with severe pelvic pain may have indeed been endometriosis, thus leading to delays in a correct diagnosis during the twentieth century.
Hippocratic doctors believed that endometriosis-
like symptoms are a result of delaying childbearing, which triggers diseases of the uterus. This may be an indirect pointer toward the existence of the disease in women with dysmenorrhea, as they were encouraged to marry at a young age and produce children so that the ectopic endometrial tissue remained quiescent. This also implies that the disease prevalence rates were higher than the 5%â15% that is often reported nowadays. If it is considered plausible that the existence of endometriosis was so common historically, we will have to reconsider the modern theories that suggest links between endometriosis and environmental toxins such as dioxins, polychlorinated biphenyls (PCBs), and chemicals [1].
Ancient descriptions suggesting the diagnosis of endometriosis
In 1999, Vincent J. Knapp [3] reported a number of old dissertations as old as the eighteenth and even the seventeenth centuries; this started a new discussion revolving around the history of endometriosis, thus focusing our attention to the exploration of womenâs diseases that had onset during the eighteenth century. On evaluation of these texts, no description of macroscopic features of endometriosis could be found. Also, it was not possible in those early times even to predict the presence of endometrial (or even epithelial) tissue in the lesions described by those authors without a microscope. Therefore, substantiating the presence of the specific features of endometriosis during the seventeenth and eighteenth centuries seems nearly impossible.
The Barker hypothesis [4] proposes that early exposures, including those arising from unhealthy lifestyles of parents, during sensitive windows of human development, such as pregnancy, may permanently reprogram the developing embryo or fetus for extra-uterine life. Thus, this theory generated considerable interest in the potential early origins of health and disease. This reprogramming is speculated to occur largely through epigenetic mechanisms [5].
In an attempt to verify the early origins of health and disease hypothesis, many investigators have assessed in utero exposures with diagnosis of endometriosis in adult women. It was demonstrated that in utero diethylstilbestrol (DES) was associated with higher odds of an endometriosis diagnosis in these women and a lesser chance of having this diagnosis with in utero exposure to cigarette smoking and increasing birth weight [6].
There has been research to document the possible role for endocrine disrupting chemicals (EDCs), defined as exogenous chemicals that can interfere with hormonal milieu in the body, including alterations in estrogen signaling [7]. The Endocrine Society published a statement on EDCs citing strong evidence of adverse reproductive outcomes following exposure, including the possibility of epigenetic changes and transgenerational effects with early exposure to these agents [8].
While speculative, this finding may suggest a role for in utero environmental tobacco smoke and endometriosis that has not been previously reported. Irrespective of route of exposure, active smoking, or passive exposure from environmental sources, the biologic dose of tobacco chemicals and metabolites may be the relevant exposure [6].
The ENDO Study was carried out with the specific aim to assess the relation between persistent environment chemicals and endometriosis [9]. There were positive associations between endometriosis and select organochlorine pesticides such as aromatic fungicides and hexachlorocyclohexane [10], polychlorinated biphenyls [11], perfluorochemicals, and dioxins. Its etiology remains unknown despite investigating a number of probable mechanisms for the same. Bisphenol A (BPA) has the ability to interact with estrogen receptors and stimulate estrogen production, being similar to endogenous estrogens, and therefore can alter gonadotropin hormone secretion [12]. Similar observations between these chemicals and endometriosis have not been substantiated by many authors in the literature, underscoring remaining critical data gaps.
Another environmental toxin widely used in plastics to increase its resilience, namely phthalate, produces anti-androgenic effects largely through the reduction in testosterone production and, possibly, reduced estrogen production at high doses [13].
It was observed that mEHP was the only phthalate consistently associated with endometriosis across cohorts, though significance was only achieved when disease was restricted to comparison women with a normal pelvis in the operative cohort. Also of note is the observation that three of the phthalate metabolites (mono (2-ethyl-5-carboxyphentyl) phthalate [mECPP], mono (2-ethyl-5-hydroxyhexyl) phthalate [mEHHP], mono (2-ethyl-5-oxohexyl) phthalate [mEOHP]) associated with endometriosis are derived from the parent compound di-(2-ethylhexyl)-phthalate (DEHP), which is the most widely used phthalate and is present in cosmetics and other personal care products that are a source of continuous human exposure [14]. Despite their relatively short half-lives, ubiquitous occurrence of BPA and phthalates may produce prolonged exposures for users, thus causing toxic levels and the related effects.
While going through the evolution of this entity, an important question often asked is, âWho identified endometriosis?â To have a plausible answer, two non-complementary methods were used: searching for ancient descriptions of similar symptoms associated with endomet...
