Embryologic Origin of Endometriosis

"The data of this manuscript give evidences for an embryological
origin of endometriosis, suggesting alterations in the fine tuning
of female genital structures organogenesis. Indeed, considering
all the 101 human female fetuses analyzed in this and in previous
works form our research group (Signorile et al., 2009b;
Signorile et al., 2010b), we found a total of nine cases of ectopic
endometrium (9% of the total). This incidence is very close to
the one found in the adult female population (Bulun, 2009).
Nevertheless, the existence of choristoma composed of
müllerian remains in adult has been codified and named
müllerianosis, even if this phenomenon has been interpreted,
but not demonstrated, as different from endometriosis (Batt
et al., 2007). In particular, we have carefully analyzed the
molecular phenotype of this ectopic endometrium, showing
that it expresses characteristic markers of the epithelium and of
the stroma of the genital tract, such as CA125, estrogen
receptor, and CD10. The histological and
immunohistochemical analysis of the eutopic and ectopic
endometrium shows a very similar phenotype, as already
in our previous works (Signorile et al., 2009b;
Signorile et al., 2010b). This observation argues against the
hypothesis that this ectopic endometrium could disappear
during the final steps of organogenesis. We propose that this
ectopic endometrium would remain quiescent and
asymptomatic until puberty, when the hormonal inputs, would
cause its growth and, consequently, the onset of the symptoms
of endometriosis.
Interestingly, several data from the scientific literature
underline the fact that the uterus of women with endometriosis
displays some congenital alterations. Parker et al. (2006),
indeed, described alterations in the muscular characteristics of
the innermost myometrium, such as the thickness and fiber
orientation and abnormal JZ morphology, securely due to the
congenital alteration of uterine wall in patients with
endometriosis. Similarly, Kunz et al. (2000) have described that
infertile women with endometriosis show alterations of the
myometrial wall with an archimetral significantly expanded.
These alterations, moreover, are identical in patients with
adenomyosis, thus supporting the concept that endometriosis
and adenomyosis are the same diseases and that the defect is
primarily at uterine level. Nevertheless, it has also been shown
that endometriosis is more frequent in patients with Müllerian
anomalies (Nawroth et al., 2006) and other genital anomalies
(Acién, 1986).
Moreover, the presence of the disease in early puberty and
exceptionally also in newborns (Diez Garcia et al., 1996; Batt
and Mitwally, 2003; Marsh and Laufer 2005; Ebert et al., 2009),
as well as in women affected by the Mayer–Rokitansky–Kü ster–
Hauser, a syndrome characterized by congenital aplasia of the
uterus and the upper part of the vagina (Enatsu et al., 2000; Yan
and Mok, 2002; Balci et al., 2008), further supports the validity
of an embryological origin for endometriosis.
Increasing experimental evidences are showing that
exposure to toxicants during critical periods of pre- and peri-
natal development can have long-lasting effects. In particular,
the ability of endocrine disruptors to alter reproductive
function and health in females are quite well characterized,
thanks especially to the numerous works on the effects of
endocrine disruptors exposition in utero (Newbold et al.,
2009). Interestingly enough, there are several studies in humans
linking exposition to endocrine disruptors with insurgence of
endometriosis (Foster, 2008). In particular, a robust
epidemiological study on a wide cohort of patients with
endometriosis has shown that the rate of endometriosis is 80%
greater among women exposed to the endocrine disruptor
diethylstilbestrol in utero (Missmer et al., 2004). In very recent
works, indeed, we have described in mice exposed in utero to
the endocrine disruptor bisphenol A the presence of
endometriosis-like structures and premature ovarian failure
(Signorile et al., 2010c; Signorile et al., 2011), a phenotype, that
strictly recapitulates the clinical picture seen in women suffering
of endometriosis. This observation is in agreement with the
work by Huseby and Thurlow (1982), that have described a
similar phenotype in mice exposed prenatally to low dose of
diethylstilbestrol: Alterations in the genital tract consisting of
adenomyosis and enlargement of the cervix, and reduced
fecundity.
In conclusion, it is possible to claim that endometriosis is a
multi-factorial disease with multifaceted features.
Nevertheless, the demonstration of the presence of ectopic
endometrium in the female fetus in same anatomical locations found in the adult patients affected by endometriosis and with a frequency very similar, makes the embryogenetic theory on
endometriosis the only one scientifically proved and suggests
that this pathogenetic mechanism is prevalent in the genesis of
this disease. Several epidemiological and animal studies, finally,
suggest an important role for an abnormal estrogenic signaling
during embryogenesis in causing the endometriosis phenotype.
Endometriosis could still be regarded as a recurrent disease;
nevertheless recurrence could not be ascribed to the
retrograde menstruation, but to an incomplete surgical
intervention, since it is demonstrated that endometriosis
lesions could be also made up of microscopic foci (Redwine,
2003), and or to different timing of growth of the lesions in the
same patient, probably due to individual susceptibility that is a
typical phenomenon of the diseases inducted by endocrine
disruptors (Mori et al., 2003). Therefore surgery, if complete in
exhausted growth disease can be considered curative.
Contrarily, exposition to endocrine disruptors such as
synthetic estrogens or SERM chemical compounds, though
reducing the symptoms, could increase the growth of
endometriosis." http://webcache.googleusercontent.com/search?q=cache:GedzAtgFjI8J:www.researchgate.net/publication/51224104_Embryologic_origin_of_endometriosis_analysis_of_101_human_female_fetuses/file/e0b4951b9b2233d071.pdf+&cd=4&hl=en&ct=clnk&gl=us

From nursingtimes.net (http://www.nursingtimes.net/nursing-practice/clinical-zones/pain-management/understanding-the-physiological-effects-of-unrelieved-pain/205262.article):

Understanding the physiological effects of unrelieved pain

16 September, 2003

Abstract

VOL: 99, ISSUE: 37, PAGE NO: 28
Carolyn Middleton, BSc, RGN, is clinical nurse specialist, Pain Service, Nevill Hall Hospital, Gwent Healthcare NHS Trust

"A noxious stimulus or pain is a stressor that can threaten homeostasis (a steady physiological state). The adaptive response to such a stress involves physiological changes that, in the initial stages, are useful and are also potentially life-saving.

Peripheral adaptation involves moving energy substrates from storage sites to the bloodstream to overcome the stressor. It also includes an analgesic response, a reflex escape response and a variety of other physiological changes mediated by the sympathetic nervous system (Johnson et al, 1992). However, if the stress response is allowed to continue, a variety of harmful effects may ensue that involve multiple systems of the body and are potentially life-threatening.

Transmission of pain
The initial physiological changes that take place within the body after a painful episode are concerned with the transmission of pain. The four basic principles that are involved are:
- Transduction: this process involves changing a noxious stimulus in the sensory nerve endings into a nerve impulse. Nociceptors (primary afferent neurones) are nerve endings with the capacity to distinguish between noxious and innocuous stimuli. When they are exposed to noxious stimuli, a number of substances, including prostaglandins, bradykinin, serotonin, substance P and histamine, are released that facilitate the movement of the pain impulse from the periphery to the spinal cord;
- Transmission: the movement of impulses from the site of transduction to the brain. Transmission occurs in three stages: from the nociceptor fibres to the spinal cord, from the spinal cord to the brain stem and thalamus, and finally from the thalamus to the cortex. For the pain stimulus to be changed to an impulse and move from the periphery to the spinal cord, an action potential must be created; that is, the movement of sodium and potassium ions from the extracellular fluid to the intracellular fluid, and vice versa. Transmission occurs in C fibres and A delta fibres and neurotransmitters are needed at each synapse to continue the pain impulse across the synaptic cleft;
- Perception: the process involved in recognising, defining and responding to pain. It is a result of neural activity and is where pain becomes a conscious experience. Perception takes place predominantly in the cortex, but the limbic system and reticular systems are also involved;
- Modulation: this involves the activation of descending pathways that exert inhibitory effects on pain transmission. Descending fibres release substances such as endogenous opioids, serotonin, noradrenaline, gamma-aminobutyric acid, and neurotensin that have the capacity to inhibit the transmission of noxious stimuli and produce analgesia (McCaffery and Pasero, 1999).

Analgesic response
The stress response includes the production of naturally occurring endogenous opioids, which are also known as encephalins and endorphins. They are found throughout the central nervous system and bind to opioid receptor sites. These substances prevent the release of neurotransmitters such as substance P and, therefore, inhibit the transmission of pain impulses, bringing about an analgesic effect. Unfortunately endogenous opioids degrade too quickly to be considered as useful analgesics (McCaffery and Pasero, 1999).

Reflex escape response
Activation of the sympathetic nervous system during an episode of acute pain is known as the ‘fight or flight’ response. The physiological responses that take place via the sympathetic nervous system and the neuro-endocrine system are numerous and intrinsically linked.

Sympathetic nervous system
The sympathetic nervous system consists of a double chain of ganglia in front of the vertebral column in the cervical, thoracic and lumbar regions, giving rise to nerves supplying the internal organs. This system is involved in the immediate bodily response to emergencies, such as severe, acute pain.
Although the initial effects of the sympathetic nervous system allow survival of an individual, prolonged activation can be detrimental (Marieb, 2000).
The sympathetic nervous system is particularly concerned with the regulation of vascular tone, blood flow and blood pressure because sympathetic nerves have a stimulating effect on the heart to improve circulation. It also has a stimulating effect on the respiratory system by causing dilation of the bronchioles to increase oxygen intake (Ganong, 1995).
The sympathetic nervous system has an inhibiting effect on digestion by reducing or preventing the secretion of digestive enzymes throughout the alimentary canal and inhibiting peristaltic action in the gut wall. It achieves all of these physiological responses via the endocrine system and an increase in hormone production (Ganong, 1995).

Neuroendocrine system
The endocrine system comprises the pancreas; thalamus; hypothalamus; kidneys; pituitary, thyroid, parathyroid, pineal and adrenal glands; and the ovaries and testes. Its principal function is to maintain internal homeostasis despite changes in the environment.
The endocrine and nervous systems work in conjunction with each other to achieve this metabolic regulation (Vander et al, 1994). Multiple hormones cooperate to bring about appropriate biochemical and physiological responses to noxious stimuli such as pain.
These stimuli activate a coordinated neuroendocrine stress response by increasing levels of certain hormones, including adrenocorticotrophic hormone (ACTH), catcholamines, antidiuretic hormone (ADH), angiotensin and glucagon. The hormones are secreted directly from the endocrine organs into the bloodstream (Fig 1).
Corticotrophin-releasing hormone
Corticotrophin-releasing hormone (CRH) is released, as a result of stimulation by noradrenaline, and transported to the anterior pituitary gland where it activates the sympathetic nervous system and stimulates ACTH biosynthesis. CRH increases blood pressure and heart rate and also produces behavioural responses to stress. Cardiovascular responses are also controlled by CRH signals (Marieb, 2000).
ACTH
The release of CRH from the hypothalamus into the systemic circulatory system stimulates the secretion of ACTH in the anterior pituitary gland. Increased levels of ACTH activate the sympathetic nervous system. However, the main function of CRH is to regulate the endocrine activity of the cortex portion of the adrenal gland so as to stimulate cortisol production and increase the levels of circulating glucocorticoids (Johnson et al, 1992).
Cortisol
Cortisol is the principal glucocorticoid that promotes normal cell metabolism. It is produced and released by the adrenal cortex in response to rising blood levels of ACTH. An increased plasma concentration of adrenal corticosteroids is the major regulator of an adaptive response to stress that, in the short term, is beneficial.
However, in the long term it is disruptive and harmful. It has a widespread effect on most organs and is particularly involved in the coordination of the actions of catecholamines.
Cortisol also has the function of maintaining blood glucose levels and energy metabolism during periods of stress. It suppresses the inflammatory response by inhibiting prostaglandin activity and has an adverse effect on the immune system. Glucocorticoids are also thought to prevent other stress-induced changes from becoming excessive (Marieb, 2000).
Adrenaline and noradrenaline
These are both catecholamines released from the adrenal medulla when it is stimulated by the sympathetic nervous system during the stress response. The adrenal medulla is not essential for life but contributes to the stress situation by secreting catecholamines, which act directly on blood vessels, causing vasoconstriction. Blood pressure then rises to allow better perfusion of vital organs, and cardiac output also increases. In addition, adrenaline and noradrenaline dilate the small passageways of the lungs to increase oxygenation (Vander et al, 1994).
Adrenaline has an effect on metabolism and has a role in the inhibition of insulin release. It also causes an increased glycogenolysis in the liver (Thomas, 1998). Finally, heightened emotional awareness occurs with increased adrenaline levels.
Glucagon
Glucagon is a polypeptide produced by the pancreatic islets in the upper gastrointestinal tract. The stress response causes glucagon levels to increase, so elevating the metabolic rate and lowering insulin levels. The result is hyperglycaemia and impaired glucose tolerance, together with carbohydrate, protein and fat destruction (Park et al, 2002). An increase in glucagon and catecholamines stimulates glycogenolysis and the release of glucose from the liver into the circulation for immediate use by critical organs, such as the brain.
Vasopressin or ADH
This hormone is released from the posterior pituitary gland. Its function is to excrete water via the kidneys. During the stress response it causes sodium and water to be retained by the renal tubules and stored in the extracellular fluid (Thomas, 1998). It also has a role in controlling blood pressure.
Renin and angiotensin II
Renin is an acid protease enzyme secreted by the kidneys into the bloodstream. Its major function is the stimulation and release of aldosterone from the adrenal gland, promoting sodium re-absorption by the kidney. Renin secretion is increased by sympathetic activity and is mediated by increased circulating catecholamines (Fig 2). Renin is also involved in the conversion of enzymes to form angiotensin II, which causes generalised arteriole constriction resulting in hypertension.
Growth hormone
Growth hormone is secreted by the anterior pituitary gland and has a direct action on cellular activity and the metabolism of protein, carbohydrate and fat. Increased protein breakdown leads to a negative nitrogen balance, resulting in reduced wound healing (Marieb, 2000).
Interleukin 1
Following tissue damage, interleukin 1 (IL-1) is released from the hypothalamus and its effects are widespread, including activation of the inflammatory effects of the immune system. IL-1 interacts with the hypothalamic pituitary adrenal axis at two levels. First, it acts in the hypothalamus to induce the production of corticotrophin-releasing factor, which mediates ACTH release. Second, IL-1 acts directly with the adrenal cortex. Both of these events lead to the release of anti-inflammatory glucocorticoids such as cortisol (Vander et al, 1994).

Effects of physiological changes
The physiological changes described above have an impact on the cardiovascular, gastrointestinal, respiratory, genitourinary, musculoskeletal and immune systems. Increased heart and breathing rates facilitate the increasing demands of oxygen and other nutrients to vital organs (O’Hara, 1996). The physiological changes that take place can also induce vomiting and potentially can pre-empt chronic pain conditions. Psychological and cognitive adverse effects are also relatively common.
Cardiovascular system
The cardiovascular system responds to the stress of unrelieved pain by increasing sympathetic nervous system activity which, in turn, increases heart rate, blood pressure and peripheral vascular resistance. As the workload and stress of the heart increase, owing to hypertension and tachycardia, the oxygen consumption of the myocardium also increases. When oxygen consumption is greater than oxygen supply, myocardial ischaemia and, potentially, myocardial infarction, occur. The myocardial oxygen supply may be further compromised by the presence of any pre-existing cardiac or respiratory disease or by hypoxaemia due to impaired respiratory function (Macintyre and Ready, 2001).
Hypercoagulation occurs when there is a reduction in fibrinolysis together with an increased cardiac rate, workload and blood pressure. This activity increases the risk of deep vein thrombosis (DVT) and pulmonary embolism (Wood, 2003).
Gastrointestinal system
Increased sympathetic nervous system activity can lead to temporarily impaired gastrointestinal function. This can include delays in gastric emptying and reduced bowel motility with the potential for the development of paralytic ileus (Macintyre and Ready, 2001).
Respiratory system
Unrelieved pain can result in a patient limiting the movement of the thoracic and abdominal muscles in a bid to reduce pain. This may cause some degree of respiratory dysfunction with secretions and sputum being retained because of a reluctance to cough. Atelectasis and pneumonia may follow (Macintyre and Ready, 2001). This pulmonary dysfunction, caused by painful excursion of the diaphragmatic muscles of the chest wall, is also associated with a reduction in vital lung capacity, increased inspiratory and expiratory pressures and reduced alveolar ventilation. The resulting hypoxia can cause cardiac complications, disorientation and confusion and delayed wound healing (Wood, 2003).
Genitourinary system
Unrelieved pain can increase the release of hormones and enzymes, such as catecholamines, aldosterone, ADH, cortisol, angiotensin II and prostaglandins, which help to regulate urinary output, fluid and electrolyte balance as well as blood volume and pressure (McCaffery and Pasero, 1999). This causes retention of sodium and water, resulting in urinary retention. Increased excretion of potassium causes hypokalaemia (Park et al, 2002). A decrease in extracellular fluid occurs as fluid moves to intracellular compartments, causing fluid overload, increased cardiac workload and hypertension (McCaffery and Pasero, 1999).
Musculoskeletal system
Involuntary responses to noxious stimuli can cause reflex muscle spasm at the site of tissue damage (McCaffery and Pasero, 1999). Impaired muscle function and muscle fatigue can also lead to immobility, causing venous stasis, increased blood coagulability and, therefore, an increased risk of developing DVT (Park et al, 2002).
Pain can limit thoracic and abdominal muscle movement in an attempt to reduce muscle pain, a phenomenon known as ‘splinting’. The lack of respiratory muscle excursion can potentially lead to reduced respiratory function (McCaffery and Pasero, 1999).
Immune system
Depression of the immune system can be caused by unrelieved pain. This may predispose the patient to wound infection, chest infection, pneumonia and, ultimately, sepsis (Wood, 2003).
Psychological and cognitive effects
Anxiety and pain are positively correlated (Johnson et al, 1992). Individuals who express unusually high levels of anxiety also tend to have a higher than expected incidence of early noxious stress. The acute stress-induced hormonal changes that have been described in this article closely resemble the symptom complex of anxiety and depression and, finally, hypercortisolism, which is a consistent feature of anxiety physiology (Johnson et al, 1992). Therefore, the stressor effects of unrelieved pain have the potential to increase anxiety levels further and interfere with activities of daily living, such as diet, exercise, work or leisure activities and to interrupt normal sleep patterns causing varying degrees of insomnia (Macintyre and Ready, 2001).
Unrelieved pain can also result in an individual experiencing distressing cognitive impairment, such as disorientation, mental confusion and a reduced ability to concentrate (Wood, 2003).
Nausea and vomiting
When pain receptors in the central nervous system are stimulated, the true vomit centre in the brain is activated, causing vomiting to occur. Disturbance of the gastrointestinal tract can activate the release of the neurotransmitter 5-hydroxytryptamine (5-HT3), which can also initiate vomiting. Initially, 5HT3 travels via the circulatory system to the chemoreceptor trigger zone in the brainstem and on to the true vomit centre, again initiating vomiting (Jolley, 2001).
Chronic pain
Poorly controlled acute pain can lead to debilitating chronic pain syndromes. Appropriate aggressive acute pain management is essential to prevent this from occurring (McCaffery and Pasero, 1999).

Conclusion
Unrelieved pain has serious side-effects, therefore the containment of such a stressor is vital. The chronic activation of the catabolic process of the stress response can ultimately cause multiple system dysfunction (Johnson et al, 1992).
Good acute pain management, including an expert knowledge of analgesic drugs and an understanding of the physiological effects of pain, is an essential element of holistic nursing care."

Studies of ECGC and Lycopene in endometriosis

ECGC from green tea has been investigated as to its effect on endometriosis. ECGC, by reducing the effects on estrogen-2 receptors, *may* help decrease the stimulation of estrogen on endo lesions, causing them to not be as big bad and ugly. I haven't been able to find the actual study (nor could I find any other studies) about lycopene, but it supposedly works by reducing proteins that contribute to adhesions.



"Green tea epigallocatechin-3-gallate (EGCG) can inhibit angiogenesis and development of an experimental endometriosis model in mice, but it suffers from poor bioavailability. A prodrug of EGCG (pro-EGCG, EGCG octaacetate) is utilized to enhance the stability and bioavailability of EGCG in vivo. In this study, the potential of pro-EGCG as a potent anti-angiogenesis agent for endometriosis in mice was investigated. Homologous endometrium was subcutaneously transplanted into mice to receive either saline, vitamin E, EGCG or pro-EGCG treatment for 4 weeks. The growth of the endometrial implants were monitored by IVIS(®) non-invasive in vivo imaging during the interventions. Angiogenesis of the endometriotic lesions was determined by Cellvizio(®) in vivo imaging and SCANCO(®) Microfil microtomography. The bioavailability, anti-oxidation and anti-angiogenesis capacities of the treatments were measured in plasma and lesions. The implants with adjacent outer subcutaneous and inner abdominal muscle layers were collected for histological, microvessel and apoptosis examinations. The result showed that EGCG and pro-EGCG significantly decreased the growth of endometrial implants from the 2nd week to the 4th week of intervention. EGCG and pro-EGCG significantly reduced the lesion size and weight, inhibited functional and structural microvessels in the lesions, and enhanced lesion apoptosis at the end of interventions. The inhibition by pro-EGCG in all the angiogenesis parameters was significantly greater than that by EGCG, and pro-EGCG also had better bioavailability and greater anti-oxidation and anti-angiogenesis capacities than EGCG. Ovarian follicles and uterine endometrial glands were not affected by either EGCG or pro-EGCG. Vitamin E had no effect on endometriosis. In conclusion, pro-EGCG significantly inhibited the development, growth and angiogenesis of experimental endometriosis in mice with high efficacy, bioavailability, anti-oxidation and anti-angiogenesis capacities. Pro-EGCG could be a potent anti-angiogenesis agent for endometriosis." http://www.ncbi.nlm.nih.gov/pubmed/22948799

"In the mouse model, both treatments significantly reduced the mean number (P < 0.05 versus control) and the volume of established lesions (P < 0.05 versus control). Treatments consistently statistically significantly diminished cell proliferation (resveratrol P < 0.01 and EGCG P < 0.05, versus control), reduced vascular density (resveratrol P < 0.01 and EGCG P < 0.001, versus control) and increased apoptosis within the lesions (resveratrol P < 0.01 and EGCG P < 0.05, versus control). Both compounds induced reduction in human EEC proliferation (P < 0.05 versus basal) and increased apoptosis (P < 0.05 versus basal) in primary cultures." http://www.ncbi.nlm.nih.gov/pubmed/23081870

 "RESULTS We found that EGCG suppresses E2-stimulated activation, proliferation and VEGF expression of endometrial cells in vitro (all P < 0.05). Furthermore, EGCG selectively inhibited angiogenesis and blood perfusion (P < 0.05) of endometriotic lesions in vivo without affecting blood vessel development in ovarian follicles. Histology confirmed that EGCG-treatment induces regression of the endometriotic lesions." http://humrep.oxfordjournals.org/content/23/10/2308.full

"'One of the major complications of endometriosis is that it causes inflammation which induces adhesions. The inflammation basically causes scarring.

'What we did was to look at protein markers that could help us trace the activity of the abnormal cells that cause these adhesions. The lycopene worked to reduce the abnormal activity of these cells.

'This means that you would not get the adhesions which suggests that lycopene could work to mitigate the complications and ailments of endometriosis. So, hypothetically speaking, we might be able to reduce the adhesion effects of endometriosis.'

Dr Dbouk said it was not possible at this stage to advise women on the amount of lycopene they should eat, but levels used in the study were similar to those that could be got from a diet packed with tomatoes and other lycopene-rich foods.

'There are many studies showing it plays a positive role in cancer and chronic inflammation, it's a nutrient and it can't do any harm,' he added.

The latest finding follows evidence that lycopene may protect against some forms of cancer, heart disease and male infertility.

The typical daily intake of a British adult is less than one milligram of lycopene, about 25 times less than the amount found by studies to protect against disease." http://www.dailymail.co.uk/.../Eating-tomatoes-fights...

Naltrexone as pain relief/anti inflammatory being explored

My doctor had mentioned low dose naltrexone before as possibility to consider for help with pain at some point in time. I wasn't really sure about it (and I haven't tried it- we discussed it before I had my surgery as a just in case) but it looks like it might could help for some people:

 "First, a growing collection of basic science studies (by investigators such as Drs. Linda Watkins and Mark Hutchinson) suggested that naltrexone can reduce the excitability of microglia in the brain, preventing the release of inflammatory and neurotoxic chemicals.

"Animal studies indicate LDN has neuroprotective properties that are directly tied to its ability to suppress microglial activation and possibly reduce inflammatory activity in the body as well.
Glial cells provide structural support for neurons in the brain, relay oxygen and nutrients to them, and defend them from pathogen attack. Once activated, the glia (or microglia) spew a wide range of inflammatory and excitatory factors (substance P, cytokines, NO, etc.) that cause such symptoms as pain, fatigue, fever, cognitive and sleep problems; in short, just about every symptom associated with Fibromyalgia and Chronic Fatigue Syndrome....The ESR findings suggest that people with inflammatory and autoimmune disorders such as lupus and rheumatoid arthritis could also benefit from low dose naltrexone.

LDN may be more effective in Crohn’s disorder (80% effectiveness rate thus far) than in FM, and may be helpful in multiple sclerosis and chronic regional pain syndrome. The authors recommended that future LDN trials include a variety of inflammatory measures such as ESR, c-reactive protein, cytokines, growth factors, etc. to explore its anti-inflammatory effects....Research into LDN has been limited, but with the first human drug trial only being published in 2007 , LDN is new to the medical community. Despite the limited research, strong clinical results and word of mouth among patients is making LDN a relatively well-known opioid alternative." http://www.cortjohnson.org/blog/2014/04/15/low-dose-naltrexone-inflammation-pain-different-approach-fibromyalgia/

Pelvic Floor- A Balance of Taut but Flexible

Regarding the pelvic floor from an interview with a biomechanical scientist:

"I like to think of the PF like a trampoline--the material is supple, but taut...the perfect muscle length....A kegel attempts to strengthen the PF, but it really only continues to pull the sacrum inward promoting even more weakness, and more PF gripping. The muscles that balance out the anterior pull on the sacrum are the glutes. A lack of glutes (having no butt) is what makes this group so much more susceptible to PFD. Zero lumbar curvature (missing the little curve at the small of the back) is the most telling sign that the PF is beginning to weaken. Deep, regular squats (pictured in hunter-gathering mama) create the posterior pull on the sacrum. Peeing like this in the shower is a great daily practice, as is relaxing the PF muscles to make sure that you're not squeezing the bathroom muscle closers too tight. Just close them enough...An easier way to say this is: Weak glutes + too many Kegels = PFD....One of the biggest misnomers is that tight muscles are "strong" and loose muscles are "weak." In actuality, the strongest muscle is one that is the perfect length - you need Pelvic Floor Goldilocks - it's juuuuuust right. The Kegel keeps making the PF tighter and tighter (and weaker and weaker). The short term benefits are masking the long term detriments. Ditch the kegels and add two to three squat sessions throughout the day (anywhere). The glutes strengthen and as a result, they pull the sacrum back, stretching the PF from a hammock to a trampoline. Viola! You can still practice opening and closing your PF in real-time situations, but you don't have to approach it like a weight-lifting session or anything....Every muscle is really a pulley that is holding your skeleton just so. When you let your glutes go, you allow the bones of the pelvis to collpase into themselves. The squat is the most effective and natural glute strengthener--using the full range of motion and your body weight. It is entirely more effective than any gym machine or contrived exercise....Athletes tend to be super-tight through the quads and psoas, which also keeps the pelvis tucked under. Wearing high heels requires women to reposition their joints to deal with the torque at the ankle, and many women will post-tilt the pelvis there as well. For optimal pelvic health, one needs to make sure the posterior muscles (glutes, hams, and calves) aren't pulling the pelvis under and keep the psoas and groin loose as well....The muscles are weak because they are tight. More "strength" or tension-increasing exercises are going to make it worse. Instead, muscle lengthening exercises--especially stretching the calves, hamstrings, groin (adductors)--are the best prescription. Also, you need to learn how to hold your pelvis correctly to optimize strength!" http://mamasweat.blogspot.com/2010/05/pelvic-floor-party-kegels-are-not.html

Talking With Your Doctor: Tips

It can be intimidating going in to talk to your doctor about a diagnosis or treatment. But they are there to help you and good communication is key to getting the most out of your healthcare. In other words "help them to help you." Here are some tips from several different sites on helping you prepare for doctor visits:

From Endojourney (http://endojourney.wordpress.com/2009/05/02/do-you-have-endo-heres-a-checklist/):

Review the following questions and consider if they apply to you.
Print this page, fill in the appropriate answers, and take this sheet to your gynecologist for further discussion.
YES NO
_____ _____ Do you experience so much pain during or around your period that you find yourself unable to work, attend school or social functions, or go about your normal routine?
_____ _____ Do you have any relatives that have been diagnosed with Endometriosis?
_____ _____ Do you find yourself with painful abdominal bloating, swelling or tenderness at any time in your cycle?
_____ _____ Do you have a history of painful ovarian endometriomas (“chocolate cysts”)?
_____ _____ Do you have a history of miscarriage, infertility or ectopic pregnancy?
_____ _____ Do you experience gastrointestinal symptoms during your cycle, such as nausea or vomiting and/or painful abdominal cramping accompanied by diarrhea and/or constipation?
_____ _____ Do you have a history of fatigue and/or a lowered immunity (i.e., “sick and tired” all the time)?
_____ _____ Do you have a history of allergies, which tend to worsen around your periods?
_____ _____ If you are sexually active, do you experience pain during sexual activity?
_____ _____ Do you suffer from any other autoimmune diseases (i.e., thyroid disease, rheumatoid arthritis, lupus, fibromyalgia, or multiple sclerosis)?
_____ _____ Have you ever undergone pelvic surgery like a laparoscopy, in which Endometriosis was suspected but not definitively diagnosed?
If you have answered “yes” to any of these questions, you could have Endometriosis.
Know the Facts:
Endometriosis can affect women and teens of all ages, even those as young as 10 and as old as 85.
Hysterectomy, menopause and pregnancy are NOT cures for Endometriosis; in fact, there is no definitive cure.
Delayed childbearing is NOT what causes Endometriosis; in fact, no one really knows for sure what causes the disease, but research points to multi-factorial origins like heredity, immunology and exposure to environmental toxicants.
Endometriosis can ONLY be diagnosed via surgery; diagnostic tests like MRIs and ultrasounds are not definitive.
GnRH therapy like Lupron should never be administered in those patients under 18 or before a surgical diagnosis.
Another good checklist is provided by the Endometriosis Foundation of America here:  http://www.endofound.org/member_files/editor_files/resource_materials/Endometriosis_Survey_Finding_a_Doctor.pdf    Also here is a symptom tracker: http://www.endofound.org/member_files/editor_files/resource_materials/Personal_Pain_Profile.pdf

Here are some tips from Agency for Healthcare Research and Quality:

"Here are some tips to help you and your doctor become partners in improving your health care.

Give Information. Don't Wait to Be Asked!

• You know important things about your symptoms and your health history. Tell your doctor what you think he or she needs to know.
• It is important to tell your doctor personal information—even if it makes you feel embarrassed or uncomfortable.
• Bring a "health history" list with you, and keep it up to date.
• Always bring any medicines you are taking, or a list of those medicines (include when and how often you take them) and what strength. Talk about any allergies or reactions you have had to your medicines.
• Tell your doctor about any herbal products you use or alternative medicines or treatments you receive.
• Bring other medical information, such as x-ray films, test results, and medical records.

Get Information

• Ask questions. If you don't, your doctor may think you understand everything that was said.
• Write down your questions before your visit. List the most important ones first to make sure they get asked and answered.
• You might want to bring someone along to help you ask questions. This person can also help you understand and/or remember the answers.
• Ask your doctor to draw pictures if that might help to explain something.
• Take notes.
• Some doctors do not mind if you bring a tape recorder to help you remember things. But always ask first.
• Let your doctor know if you need more time. If there is not time that day, perhaps you can speak to a nurse or physician assistant on staff. Or, ask if you can call later to speak with someone.
• Ask if your doctor has washed his or her hands before starting to examine you. Research shows that handwashing can prevent the spread of infections. If you're uncomfortable asking this question directly, you might ask, "I've noticed that some doctors and nurses wash their hands or wear gloves before touching people. Why is that?"

Take Information Home

• Ask for written instructions.
• Your doctor also may have brochures and audio tapes and videotapes that can help you. If not, ask how you can get such materials.

Once You Leave the Doctor's Office, Follow Up

• If you have questions, call.
• If your symptoms get worse, or if you have problems with your medicine, call.
• If you had tests and do not hear from your doctor, call for your test results.
• If your doctor said you need to have certain tests, make appointments at the lab or other offices to get them done.
• If your doctor said you should see a specialist, make an appointment.

Remember, quality matters, especially when it comes to your health....

Your Doctor Is Your Partner in Health Care

You probably have many questions about your disease or condition. The first person to ask is your doctor.
It is fine to seek more information from other sources; in fact, it is important to do so. But consider your doctor your partner in health care—someone who can discuss your situation with you, explain your options, and help you make decisions that are right for you.
It is not always easy to feel comfortable around doctors. But research has shown that good communication with your doctor can actually be good for your health. It can help you to:

• Feel more satisfied with the care you receive.
• Have better outcomes (end results), such as reduced pain and better recovery from symptoms.

Being an active member of your health care team also helps to reduce your chances of medical mistakes, and it helps you get high-quality care.
Of course, good communication is a two-way street. Here are some ways to help make the most of the time you spend with your doctor:

Prepare for Your Visit

• Think about what you want to get out of your appointment. Write down all your questions and concerns. (Select for a list of suggested questions.)
• Prepare and bring to your doctor visit a list of all the medicines you take.
• Consider bringing along a trusted relative or friend. This person can help ask questions, take notes, and help you remember and understand everything once you leave the doctor's office.

Give Information to Your Doctor

• Do not wait to be asked.
• Tell your doctor everything he or she needs to know about your health—even the things that might make you feel embarrassed or uncomfortable.
• Tell your doctor how you are feeling—both physically and emotionally.
• Tell your doctor if you are feeling depressed or overwhelmed.

Get Information from Your Doctor

• Ask questions about anything that concerns you. Keep asking until you understand the answers. If you do not, your doctor may think you understand everything that is said.
• Ask your doctor to draw pictures if that will help you understand something.
• Take notes.
• Tape record your doctor visit, if that will be helpful to you. But first ask your doctor if this is okay.
• Ask your doctor to recommend resources such as Web sites, booklets, or tapes with more information about your disease or condition.

Go to: Ten Important Questions to Ask Your Doctor After a Diagnosis.

Do Not Hesitate To Seek a Second Opinion

A second opinion is when another doctor examines your medical records and gives his or her views about your condition and how it should be treated.
You might want a second opinion to:

• Be clear about what you have.
• Know all of your treatment choices.
• Have another doctor look at your choices with you.

It is not pushy or rude to want a second opinion. Most doctors will understand that you need more information before making important decisions about your health.
Check to see whether your health plan covers a second opinion. In some cases, health plans require second opinions.
Here are some ways to find a doctor for a second opinion:

• Ask your doctor. Request someone who does not work in the same office, because doctors who work together tend to share similar views.
• Contact your health plan or your local hospital, medical society, or medical school.
• Use the DoctorFinder online service of the American Medical Association. Go to: http://dbapps.ama-assn.org/aps/amahg.htm .

Get Information About Next Steps

• Get the results of any tests or procedures. Discuss the meaning of these results with your doctor.
• Make sure you understand what will happen if you need surgery.
• Talk with your doctor about which hospital is best for your health care needs.

Finally, if you are not satisfied with your doctor, you can do two things:

1. Talk with your doctor and try to work things out.
2. Switch doctors, if you are able to.

It is very important to feel confident about your care."   http://www.ahrq.gov/patients-consumers/diagnosis-treatment/diagnosis/diaginfo/diaginf4.html

Modified from Cancer.net (http://www.cancer.net/navigating-cancer-care/diagnosing-cancer/questions-ask-doctor):
(good for after surgical diagnosis)

"Where exactly is it located?

What are the risk factors for this disease?

Is this caused by genetic factors? Are other members of my family at risk?

What lifestyle changes (diet, exercise, rest) do you recommend I make to stay as healthy as possible?

Where can I find more information?

Symptoms

• What are some common symptoms or side effects?
• How can I avoid these and/or manage them with my daily activities?
• Is there anything that can be done to make my symptoms or side effects better?
• Are there activities that may make them worse?
• If new symptoms or side effects arise or existing ones worsen, what should I do?

Diagnosis

• What diagnostic tests or procedures are necessary? How often?
• What information will these tests tell us?
• How can I prepare myself for each test or procedure?
• Where do I need to go to have this test?
• When will I get the results? How will I get the results (over the phone, at the next appointment, etc.)?
• Can you explain my pathology report (laboratory test results) to me?
• If I seek a second opinion, will I have to repeat any tests or procedures?

Treatment

• What are my treatment options?
• Which treatments, or combination of treatments, do you recommend? Why?
• What is the goal of the treatment you are recommending?
• What clinical trials (research studies involving people) are open to me?
• Who will be part of my treatment team, and what does each member do? (pelvic physical therapy for example)
• How much experience do you (or the treatment team) have treating endometriosis?
• What is the expected timeline for my treatment plan?
• How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
• What are the short-term side effects of this treatment?
• What long-term side effects may be associated with this treatment?
• Will this treatment affect my fertility?
• What can be done to treat my symptoms?
• How can I keep myself as healthy as possible?

Support

• What support services are available to me? To my family?
• Whom should I call with questions or concerns during non-business hours?
• May I contact you or the nurse to talk about additional information I find?
• Where can I find resources for teenagers? For young adults?
• If I'm worried about managing the costs related to my care, who can help me with these concerns?
• Who handles health insurance concerns in your office?

Follow-up care

• What follow-up tests do I need, and how often will I need them?
• Is there anything else I should be asking?"

From CNN (http://www.cnn.com/2013/01/16/health/doctors-listen/): 

"1. Tell your whole story. Studies have shown that more than 80% of diagnoses can be made based on history alone. Unfortunately, doctors sometimes seem to want to steer you toward a cookbook "chief complaint" or a series of "yes/no" answers. Learn to tell a succinct, effective story. Prepare and rehearse it.

2. Assert yourself in the doctor's thought process. Find out what your doctor is thinking as you recount your history, and let your doctor know what's on your mind. If you're not starting out on the same wavelength, it's hard to develop that crucial partnership.

3. Participate in your physical exam. If you're being examined, make sure you know what the doctor is looking for. Don't be afraid to ask about the implications of any findings.

4. Make a differential diagnosis together. A "differential diagnosis" is just the list of all the possible diagnoses that could explain your symptoms. Make sure you and your doctor come up with a thorough list, with some estimate of the likelihood of each possible diagnosis. Keep asking what else could be going on.

5. Partner in the decision-making process. Devise a strategy with your doctor for narrowing down the list of possible diagnoses. By partnering with your doctor, you can often arrive at a working diagnosis without a lot of tests.

6. Apply tests rationally. If you do need to undergo further testing, you should understand how a particular test will help narrow down your differential and what the risks and alternatives are. Look out for "cookbook medicine," and make sure your doctor is tailoring an approach that works for you.

7. Use common sense. You shouldn't leave the doctor without a working diagnosis that makes sense to you. Don't just assume the doctor must be right. If the picture doesn't add up, go back to the drawing board.

8. Integrate diagnosis into the healing process. Talk through your diagnosis with your doctor and make sure you understand its predicted course. What treatment options do you have, and what risks and benefits do they carry? If your working diagnosis turns out to be wrong, what warning signs should you be on the lookout for?"  http://www.cnn.com/2013/01/16/health/doctors-listen/

 

Talking to your doctor can be intimidating. It's important to get the most out of your visits. Doctors are busy and have a vast array of patients to care for. Even with detailed notes in your chart, they may not remember your case history perfectly. Make it easy on them and you too. Here are some tips to help you prepare for your next doctor's visit from http://www.anapsid.org/cnd/diagnosis/canwetalk.html: 

"Before The Visit
Organize ahead of time Keep a list on the refrigerator, by your bedside, or in your purse. Jot notes about symptoms or questions as soon as they arise. A day or two before your visit organize your notes. Be as specific as possible. For "my arm hurts", you might describe the problems holding your arms up for hair drying, lifting children, or hanging laundry. Highlight the items that are particularly worrisome.
Identify goals for the visit What do you hope to accomplish with your doctor? A diagnosis? Referral to a specialist? Report new symptoms?
Prioritize your goals, listing your primary reason for this appointment first. How many problems should you talk about at a visit? Two to five, depending on the time allotted and the complexity of the problems.
Other notes to makeMake as many lists as you need to organize all the information and questions you need to communicate to your doctor:

• Current medication list: including prescription, over-the-counter, herbal supplements, vitamins, topical medications, alternative medications and treatments; allergies and previous adverse reactions; prior medications and why they didn't work.

• Problem list: a complete but concise summary of your medical history. Rank conditions in order of importance, with the most important first. Give dates, if possible. Example: Fibromyalgia - 1990, migraines - 1992, gall bladder removed - 1986.

• Specialist list: summarize latest recommendations. Example: Gynecologist - August 2002 - hormone replacement started.

• Recent tests: include dates and locations. Always ask for copies of your test results so you can have them for your own files.

• Changes in symptoms since your last visit

• Questions for today

• Refills needed

• Forms to be completed (with an SASE for return or sticky note with your telephone number)

Bring your lists! If you forget, ask the receptionist for paper and start writing while you wait. Keep copies of your problems and medication lists in your purse or car in case of emergency and update them regularly.

At The Doctors Office
Speak up: Being part of a team requires trust and clear, open communications. Be frank, even if it's embarrassing. Hand your doctor your lists, so he knows what you want to discuss today. Remember your goals for this visit. Voice your ideas. It is best to ask questions as soon as they arise.
Clarify: Use words such as "exactly" or "specifically". Ask: How will this help me? What will happen if I don't do this? When you say to increase activity, exactly what kind and how often? Does exercise mean weights or walking? What do you mean by "come back if not better"? When and how much better?
Negotiate: Request a cheaper drug or one with fewer side effects and less risk. Ask for an easier regimen or a less painful procedure. If a suggestion is unrealistic for you, say so - don't leave discouraged because you can't do it all. Doctors can simplify or adjust treatments so you can live with the recommendations. And remember: it's okay to think about your decision or change your mind. Never be pressured or scared into an action. Short of a life-threatening emergency, there is always time to think things through.

What can get in the way? Knowing the factors that impede effective communication is half the battle. Emotions, communication style, differing expectations, and lack of time all work against us. When emotions are high, logic is low. The shock of a new diagnosis, fear, embarrassment, resentment, intimidation, and forgetfulness (fibrofog) can all jumble our thoughts. With pain and fatigue, you might not be functioning at your highest level. If you find emotions interfering with your visit, honestly state how you feel. Naming the emotion takes some of the punch out of it. Ask for a moment to compose yourself, count to 10 and breathe slowly and deeply. Begin again if you are able or wait for another time. Consider also that a chronic illness frustrates doctors as well as patients. Although your doctor wants to help, he may feel there is little he can do for you.
Poor communication frequently results when we assume too much. Just as "straighten up your room" has both a parent and a teen interpretation, failure to clarify medical directions may result in differing expectations for you and your physician. For example, assuming your test results will be normal unless you are called could be a deadly mistake. Rather than assume, specify. Request a simpler explanation. If you learn best by seeing or reading rather than hearing information, ask your doctor to draw a diagram or give you a brochure. Ask him to slow down or confirm details. Repeat any instructions he gives you and write everything down or tape record it.

Streamlining your visit No doubt about it, time is a huge factor in poor communications for today's healthcare providers. In an ideal world, a doctor would have enough time to answer all questions clearly. Since this rarely happens, how can you use your time with your doctor wisely? Studies show that you have 23 seconds to speak before the doctor interrupts, so weed out the irrelevant details. For example, state, "I passed out last night. They took me to the emergency room." Stop right there! Don't add, "And it was really cold in the ER and the nurse looked at me like she'd never heard of fibromyalgia and…" Unless you have more symptoms to add, let your doctor ask you questions. Refer to the list of concerns you brought with you to make sure you have all of them covered.
If there is not enough time to cover everything, request handouts and brochures that will provide you with information. Then schedule another visit with more time to fully discuss your concerns.

Before you leave Ask the doctor for written instructions. Summarize and make sure to clarify anything you aren't familiar with. Don't leave without fully understanding your diagnosis and treatment. If the doctor has left the room, ask a nurse.

Outside The Office
I forgot to ask… Realistically speaking, questions come to mind outside of the office. If your problem is urgent, call the office right away. Otherwise, check first to see if your question can be answered in a brochure given to you by your doctor. Consult your pharmacist for medication questions. Are you tempted to ask your chat room support group for advice instead? The Internet is a great place for researching information to discuss with your doctor, but relying on online information for medical answers can be dangerous.
Communicating by telephone The office RN can handle most questions. Call early in the day, but be aware that your call may not be returned until the end of the day. It is helpful to compose a one sentence description of the problem, including symptoms and dates. Have medication bottles handy as well as your pharmacy phone number. Write down your questions and have a paper and pencil handy to record instructions. Inform the office if family members may receive information.
Communicating by e-mail The majority of families with computer access want to communicate with physicians via email. Physicians generally are less comfortable with that route. Both sides have concerns about confidentiality. Some benefits of email include: ending telephone tag, speed, cutting costs, more detailed medical records, fewer medical errors, and improved compliance. Risks include: privacy and security, as well as physician concerns of staff workload, reimbursement and malpractice liability. More importantly, access to care might be determined by computer literacy. At present, most doctors do not offer email communication, but it pays to ask.
Communicating by Fax Transmitting messages via Fax provides many of the same advantages as email. Access to a fax machine (or directly from your computer with PC-fax software, allows you to send detailed, accurate communications. Fax is an especially good method when you have multiple requests and is an excellent way to receive your lab results from the office. Bear in mind that confidentiality is an issue when using shared office equipment.
You have the right to remain silent - but don't! Communication is a two-way street and it starts with you. Speak up! You have the right to understand your diagnosis, your symptoms, tests, procedures and all the risks and options. Your doctor has the responsibility of treating you with respect, listening, addressing embarrassing questions, educating, informing and considering your opinions and concerns. You are responsible for coming to scheduled appointments, taking your medication as prescribed, reporting adverse effects, becoming knowledgeable about your disorders, informing your doctor about your symptoms, progress, questions and concerns. Communication is an especially important skill for fibromyalgia patients. Make every word count!

Pointers For Successful Communications
Pointer 1: Talking about pain Mention where, how much (use a scale of 1-10), what makes it better or worse, description (tingly, achy, knife-like), medications used and, most importantly, the impact on your daily functioning. Decide on your pain management goals. "I need better pain control" could mean completely pain-free (but possibly sleepy) or it could mean enough pain control to be able to play with your grandchildren, work 20 hours a week, or sleep comfortably. You and your doctor need to be working towards the same goals.
Pointer 2: Talking about tests Discuss the reason for the test (diagnosis? Change in treatment?), method, accuracy, preparation, pain involved, when to expect results and insurance coverage. Test results are written in medical-ese, language that can be misinterpreted by non-medical people and well-trained medically knowledgeable friends. Ask your doctor to explain the wording in simple terms. Do not settle for a glossing over such as "that's nothing to worry about."
Pointer 3: Talking about medication Know the medication's purpose, how to take it (with food, time of day, when to stop), adverse effects, interactions with other medications, when it should take effect, and cost. Make sure you can read the prescription: if you can't, the pharmacist might not be able to either. To minimize errors and complications, it's a good idea to have one doctor all of your prescriptions, even specialty medications.
Pointer 4: Talking about alternative/complementary therapies (ACTs) Present articles from reliable sources, discuss pros and cons, and determine compatibility with your medications. Understandably, doctors are hesitant to advocate ACTs without scientific testing. However, your doctor may agree to a trial if the treatment has not been shown to be harmful. Obtain a prescription or letter of medical necessity, if possible, because insurance companies sometimes covers alternative therapies.


...Depending on your level of pain, fatigue and brainfog on any given day, even very simple, explicit instructions can be mind-boggling and impossible to understand. There is a limit to how much time the doctor, nurses or other staff can spend with you go to over and over and over something. If you can't bring someone with you who can be your brain then bring a tape recorder and tape your session with the doctor and anyone else you ask for clarification on the instructions or information you were given.
If you are seeing different doctors, they all need to know about all of the prescription medications the other doctors have prescribed, as well as all of the over-the-counter, vitamins, minerals, herbs, alternative preparations, enzymes, aminos, pre- and probiotics you are taking. Many symptoms that may be ascribed to your illnesses may in fact be adverse interactions between the various drugs, supplements, herbs, etc. that you are ingesting every day.
Make and keep updated a master list of all the medications (prescription and OTC, topical and oral), vitamins, minerals, herbs, herbal teas, and other products you are ingesting. You will want this not only for your records but so that you can easily print it out and take it with you to each new doctor you are seeing. Give updated copies at least once a year to your regular physician, dentist and other healthcare providers.
Keep all your receipts for all of these medications and products, and copies of your notes on their use, especially when you've discussed them with your doctor. The receipts and notes will provide the back up when you claim them as medical deductions on your income tax as well as document the fact that you are "trying" to get better when you are hit with a social security or long-term disability review, an event that may happen once every three years or so until you reach retirement age."
 http://www.anapsid.org/cnd/diagnosis/canwetalk.html