Table 3.

Evidence that causes of endometriosis represent actual or potential treatments for PCOS, and vice versa

Treatment or cause of endometriosis or PCOS	Effect in endometriosis	Effect in polycystic ovary syndrome	Comments	References (see text for additional details)
Danazol, a synthetic androgen with high affinity for the androgen receptor	Used to alleviate symptoms of endometriosis; administered orally or vaginally; has androgenic side effects (e.g., hirsutism)	High androgen levels are a primary cause of PCOS; flutamide, an antagonist of the androgen receptor, is used to treat PCOS	Ovarian and serum testosterone are lower in women with endometriosis than in controls, and higher in women with PCOS than in controls	[3, 49, 67, 140, 144]
Valproate, a histone deacetylase inhibitor that suppresses aromatase, used mainly to treat epilepsy and bipolar disorder	Treatment reduces endometrial lesion size in rat model and reduces proliferation of endometrial stromal cells in vitro. Also reduces menstrual pain in women with adenomyosis, a condition similar to endometriosis	Treatment induces major symptoms of PCOS, including increased serum testosterone	A histone deacetylase inhibitor similar to valproate, trichostatin A, induces apoptosis of endometrial cells derived from women with endometriomas	[145–147]
Oxytocin or oxytocin antagonist (i.e., Atosiban)	Atosiban treatment reduces size of endometriotic implants in rat model of endometriosis; also increases pregnancy rates in women with endometriosis undergoing embryo transfer	Oxytocin treatment alleviates obesity-related metabolic traits in rat model of PCOS, and may reduce obesity in women	Serum oxytocin levels are lower in women with PCOS and higher in women with endometriosis; oxytocin mediates food intake, metabolism and uterine smooth muscle peristalsis	[148, 149]
Letrozole, an aromatase inhibitor	Used to treat endometriosis; reduces size of endometriosis implants and pain	Used to generate PCOS in rodent models	Aromatase expression is typically elevated in endometriotic tissue, and reduced in ovarian tissue in PCOS	[150–152]
Mifepristone, a progesterone receptor antagonist	Used to treat endometriosis; reduces size of endometriosis implants and levels of pain	Used to generate PCOS in rodent models	Mifepristone increases the LH/FSH ratio and testosterone/estrogen ratio in rat model and upregulates androgen receptor in human endometrial biopsy tissue	[153]
Opiates and opiate receptor antagonists (naloxone and naltrexone)	Opioids used for pain in endometriosis also modulate HPO axis and may affect endometrial proliferation	Naloxone and naltrexone alleviate PCOS symptoms in humans and in animal models; naltrexone reduces testosterone and LH	Levels of β-endorphins are higher in PCOS, lower in endometriosis, compared to controls; opioid receptors are expressed in endometrial tissue	[154–157]

The table does not include medications for endometriosis (e.g., GnRH agonists, and oral contraceptives) that involve dampening or deactivation of the HPO axis and cessation of menstrual activity, because these do not treat the disorder itself.