Pathophysiology of Endometriosis
and conventional treatment
Endometriosis is a chronic inflammatory condition.12 It is associated with under-methylation, oestrogen excess and progesterone resistance26. It may also be considered a neurovascular condition like headache.12
In a chicken and egg scenario, excessive oestrogen causes proliferation and inflammation and inflammation causes up-regulation of oestrogen producing enzymes. These enzymes include aromatase, sulphatise and 17-beta hydroxysteroid dehydrogenase (17βHSD) and have the ability to convert dehydroepiandrosterone (DHEA) into androgenic hormones and bind, low potency forms of oestrogen into proliferative oestradiol (E2).26,28 Endometriotic growths can generate aromatase.8
Oestrodial can be synthesized at a number of sites within the body, the primary one is the ovary, secondary sites are in peripheral tissues such as adipose tissue, skin and skeletal muscle and thirdly, in women with endometriosis, oestrodial is produced by endometriotic tissue thus creating a self-perpetuating source of inflammation27.
There is an imbalance in oestrogen receptors with an over expression of oestrogen receptor-β (ER-β) and under expression of oestrogen receptor-α (ER-α). This may be caused by hypo-methylation of ER-β which causes this receptor to become overactive. ER-α is a primary mediator of oestrogenic action in the endometrium and is linked to the ability of tissues to respond to progesterone.26,27 High levels of ER-β and low levels of ER-α leads to increased oestradiol and under expression of progesterone receptors (PR), therefore progesterone resistance.26
Types of endometriosis are categorised as superficial peritoneal endometriosis, deeply infiltrating endometriosis (DIE) and ovarian (cystic) endometriosis.12
Endometriotic growths have an ability to create new nerve endings and independently affect the central nervous system (CNS).12,35 It is thought the vascularisation of lesions leads to neural sprouting of nerves to innervate the new blood vessels. Nerve growth factor (NGF) is implicated in producing the pain associated with endometriosis, it is associated with transforming growth factor beta -1 (TGFβ1) and is more commonly found in DIE or red lesions. Lesions may also produce pain by compressing or infiltrating nerves near lesions.12
High levels of cyclo-oxygenase-2 (COX-2), pro- inflammatory cytokines, prostaglandins and chemokines are found in women with endometriosis.27,35 These inflammatory agents are implicated in the sensitization of sensory nerve fibres that exist on or near ectopic endometriotic growths.12,35 C-fiber nociceptors are included in the innervations of lesions, once sensitized they remain active i.e. transmitting pain signals, even when inflammation is resolved.12 In turn, central sensitization and hyper-excitability of the CNS is produced thus explaining ongoing pain in women who have had endometriotic growths surgically excised or shrunk by endocrine agents.12,35
Endometriosis is associated with the formation of adhesions.12 It is these adhesions that are implicated in infertility due to creating obstructions. When present in the rectouterine pouch, the pain women experience is much worse. Adhesions and scarring may also be exacerbated by surgical techniques to remove endometriotic growths.
Conventional Treatment
The aim of conventional medical treatment is to manage the presenting symptoms, there is no medical cure. Treatment “efficacy is short-term and recurrence is common in both medical and surgical modalities.”6 “In most cases, pain recurs within 6 to 12 months after completion of treatment.”8
The oral contraceptive pill (OCP) and non-steroidal anti-inflammatory drugs (NSAIDs) are the first line of treatment in conventional medicine. Other endocrine agents are then utilized with the aim to control the menstrual cycle and hence the proliferation of endometriotic tissue.
An interesting article states that the use of NSAIDs are of little use in treating the pain of endometriosis and may be no better than placebo.8
The Progesterone only pill such as Depro Provera (depot medroxyprogesterone acetate - DMPA) induces a state of stimulated pregnancy which prevents cycling of the endometrial tissue.5 It is thought that by doing this, the ectopic endometrial tissue will shrink or die off completely. The treatment is issued for 6 months and symptoms should be resolved for at least 12-18 months post medication. This treatment is beneficial for less than 50% of women.26 The same idea is behind the use of the levonorgestrel intrauterine system.8
Another hormone treatment is the use of GnRH analogues (e.g. leuprolide acetate) which then suppress the whole cycle from the hypothalamus. This is referred to as a hypogonadal state, the ovaries are essentially “switched off”, production of other androgens is also suppressed.4 This treatment has been associated with osteoporosis with as much as 13% bone loss after 6 months of use8 and bone mineral densitometry is carried out to monitor bone loss.4,5. GnRH with add-back oestrogen and progesterone is now the treatment of choice to reduce this undesirable side effect.3,4. Other side effects occur akin to those experienced by many women during menopause e.g. hot flashes, dry vagina, low libido, irritability, fatigue and depression.4
Surgical treatment generally involves fulguration or excision of endometriotic tissue within the pelvic cavity via laparoscopy.8 This may alleviate symptoms for a while but as microscopic lesions are missed, the recurrence of endometriosis occurs within 6 to 24 months, longer when combined with GnRH therapy.8 The procedure is very dependent on the skill of the surgical practitioner.
As a last resort, many women opt for surgical removal of the uterus and ovaries in an effort to be free of symptoms. Without addressing the underlying cause that set up the disease condition in the first place, this may not be the last chapter. It is possible that a woman who has had a hysterectomy will later develop Ménière’s Disease. This is explained via iridology, we see that issues in a given reference area of the iris show as an energy imbalance in the reference area opposite. Opposite the uterus reference area is the area for equilibrium13.
Other drugs are administered to deal with concomitant symptoms. This may include
Anti-cholorgenic drugs e.g. tolterodine, oxybutinin to help with painful bladder problems
Tricyclics antidepressant drugs e.g. amitriptyline in small doses to help with pain
Antihistamines e.g. hydroxyzine for PBS, especially if associated with allergies, cyproheptadine for migraine
Anticonvulsant medications e.g. gabapentin, pregabalin to help with neurologic pains.
Non-steroidal anti-inflammatory drugs e.g. diclofenac
These drugs create their own disease due to side effects.
This is taken from my thesis written in 2016. References are available on request. Next post will cover the nutritional recommendation for endometriosis.