Adrenal-thyroid-immune dysfunction as a cause of reproductive failure in pets: does a veterinary syndrome offer testing and treatment insights for infertility and miscarriages in humans?

Townsend Letter for Doctors and Patients, Dec, 2004 by Alfred J. Plechner

As a clinical veterinarian, I repeatedly resolve infertility and miscarriages in dogs and cats by correcting a common but overlooked syndrome of hormonalimmune dysfunction originating with defective or deficient production of cortisol. The key ingredient in the corrective program involves a standard medicine used in a different way, and this approach may possibly offer insights for exploring an alternative, inexpensive treatment for reproductive failures in humans.

In the 50 plus years since first appearing in the medical marketplace, the pharmaceutical derivatives of cortisol--that is, cortisone (steroid) compounds--have become prominent mainstream medicines because of their clinically important anti-inflammatory and immune suppression applications. Over the years we have also learned a great deal about the side effects of these compounds--and come to fear them--when used at typically powerful, pharmacologic dosages. For that reason steroids are usually prescribed for the short-term and avoided for prolonged use.

This development has discouraged interest in the pivotal physiologic roles of cortisol and applications of low-dosage cortisone as a "hormone replacement" for cortisol deficiency. Such deficiencies tend to be off the radar screen of most practitioners even though common among both animals and humans as a result of genetic and/or acquired factors including toxicity and prolonged stress. This is a major omission. Research tells us that immunity appears to be regulated by the hypothalamic-pituitary-adrenal (HPA) axis, (1) thus making normal health and reactions to stress and infections critically dependent on the ability of the adrenal glands to produce a proper quantity of cortisol.

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In thousands of feline and canine cases, I have consistently identified a cortisol defect that kindles a domino effect of hormonal disturbances leading to immune deregulation and systemic dysfunction. (2-4) This "disabling" mechanism sets the stage for multiple disorders ranging from chronic allergies and viral diseases to autoimmunity and cancer. The innovative blood tests I conduct to demonstrate the presence of this pattern of disturbance are usually quite revealing in animals--including horses who have been tested--with a history of infertility and miscarriages.

The signature pattern involves an initial deficiency of active cortisol plus elevated total estrogen, bound thyroid hormones, and low concentrations of immunoglobulins IgA, IgG, and IgM. I find this same pattern in intact or neutered male and female animals. I believe that the elevated estrogen stems from disturbance of the HPA feedback loop. The adrenal cortex, unable to produce adequate cortisol, causes prolonged release of pituitary ACTH. This in turn stimulates estrogen directly from the adrenal cortex or from adrenal androgen conversion to estrogen in peripheral tissue.

The combination of deficient cortisol and excess estrogen destabilizes the immune system but also has considerable potential to interfere with thyroid function. The medical literature contains considerable data linking thyroid function and reproduction. Indeed many cases of infertility are treated with thyroid medication. However, thyroid hormones--both endogenous and as medication--may be rendered ineffective to some degree by abnormal levels of cortisol and estrogen that can bind thyroid compounds in the body, impair their cellular uptake, and interfere with T4>T3 transference. (5-7) Thus, a slowing of metabolism can occur that might affect reproduction and even the body's ability to remove excess estrogen.

Low thyroid function in males is associated with impotence, loss of sperm production and motility, and abnormal morphology. I often see this in intact male dogs and cats with endocrine-immune imbalances who are infertile.

Intact female dogs and cats with the same pattern of imbalances frequently develop endometriosis, cystic ovaries, and periods of excess hemorrhaging, an apparent result of elevated estrogen. During a normal pregnancy period of 62 to 65 days, such animals may miscarry. Sometimes gross fetal abnormalities develop, including small, mummified fetuses, followed by resorption. Could this be due to an estrogen-induced inflammation of the uterine lining? In these female animals estrus is often not noticeable. There is no vaginal engorgement or bleeding, a condition referred to as "silent heat."

Standard blood tests of affected male and female animals often indicate normal levels of thyroid hormones but the action of these hormones appear to be bound, blocked, or otherwise hampered by elevated estrogen and low cortisol.

The hormonal disturbances compromise the immune system in general. Locally, the ability of the uterus to protect itself appears to be weakened. The blood tests I conduct consistently reveal a low IgA level. Most practitioners pay little attention to IgA, yet IgA is the most abundant antibody and is especially important in mucosal immunity. It is an essential protective factor against infectious agents, allergens and foreign proteins that enter the body via the mouth, nose and upper respiratory tracts, the intestines, and reproductive tract. IgA deficiency is the most frequent immunodeficiency in humans. (8)

Clinically, I regard a low IgA test score as a marker of impaired immunity in the mucous membranes, including the uterus and ovaries. The low value makes it evident to me why these tissues are vulnerable to inflammation and infections, and less able to "host" normal reproduction.

In veterinary medicine, the cause of such pathology is frequently attributed to an infected male carrying brucella canis, a bacteria that can cause infertility and abortion. However, these microorganisms are usually not found.