Friday, August 1, 2014

Estrogen and the thyroid

"Estrogen has a well-known indirect effect on thyroid economy, increasing the thyroxine binding globulin [4], and the need for thyroid hormone in hypothyroid women [5]."

Interesting- the thyroid has estrogen receptors:

(Note: ER = estrogen receptor)
"Classically, the presence of ER is fundamental for a direct action of estrogen in a given cell. ER has been described in both neoplastic and nonneoplastic human thyroid tissues ....An important role of different patterns of distribution and expression of subtypes ERs in thyroid carcinoma has been proposed: estrogen binding to ERα would promote cell proliferation and growth, and, in contrast, ERβ would promote apoptotic actions and other suppressive functions in thyroid tumors, as reviewed by Chen et al. [40]. Then, ERα:ERβ ratio could have a role in the pathophysiology of thyroid cancer [40], similar to that postulated for breast cancer [41].... Several studies described proliferation of thyroid cells induced by E2... These results, together with the increase in cell growth caused by estrogen, could implicate this hormone in the pathogenesis of goiter and thyroid carcinoma; nevertheless, as just one study evaluated the effect of estrogen on thyroid differentiated proteins in human thyroid tissue, more studies should be done to better understand the role of estrogen in thyroid differentiated protein expression.... There are evidences that estrogen may have direct actions in human thyroid cells by ER-dependent mechanisms or not, modulating proliferation, and function. Different patterns of distribution, expression, and ratios of ERα and ERβ may have a role in thyroid cancer cells proliferation, as well as in the outcome of thyroid cancer. Studying estrogen effects on thyroid cells is a potential tool to better understand the pathogenesis of thyroid diseases, and to develop targets to its treatment. Further studies on the influence of E2 on the growth and function of the thyroid are needed, preferably in primary culture of normal and abnormal human thyroid cells."

"Because of its hepatic first-pass effect, oral estrogen therapy, the most commonly used modality of ET/HT, raises the circulating levels of thyroxine-binding globulin (TBG), thereby increasing the bound fraction and decreasing the free (bioactive) fraction of circulating thyroxine (T(4)). As a consequence, oral ET/HT may increase the T(4) dosage requirements of women being treated for primary hypothyroidism as well as alter the pituitary-thyroid axis in euthyroid women."

"But other factors not commonly considered when people think of “stress” place just as much of a burden on the adrenal glands. These include blood sugar swings, gut dysfunction, food intolerances (especially gluten), chronic infections, environmental toxins, autoimmune problems and inflammation. All of these conditions sound the alarm bells and cause the adrenals to pump out more stress hormones. In this context, stress is broadly defined as anything that disturbs the body’s natural balance...

"Cortisol is one of the hormones released by the adrenals during the stress response. Prolonged cortisol elevations, caused by chronic stress, decrease the liver’s ability to clear excess estrogens from the blood. Excess estrogen increases levels of thyroid binding globulin (TBG), the proteins that thyroid hormone is attached to as it’s transported through the body.

When thyroid hormone is bound to TBG, it is inactive. It must be cleaved from TBG to become “free-fraction” before it can activate cellular receptors. (These free-fraction thyroid hormones are represented on lab tests as “free T4 [FT4]” and “free T3 [FT3]“.)

When TBG levels are high, the percentage of free thyroid hormones drops. This shows up on labs as low T3 uptake and low free T4/T3.

Aside from adrenal stress, the most common causes of elevated TBG secondary to excess estrogen are birth control pills and estrogen replacement (i.e. Premarin)."

Birth control pills and thyroid:

"In women with hypothyroidism treated with thyroxine, estrogen therapy may increase the need for thyroxine."

"Certain medicines can affect the way thyroid medicines work. People taking the following medicines need to see their doctor often to make sure they are getting the correct dose of thyroid hormone medicine. Some of these medicines include:
"Common laboratory tests used in the assessment and diagnosis of thyroid disorders include measuring the circulating thyroid hormone concentrations, evaluating the integrity of the pituitary negative-feedback system, measuring thyroid antibody concentrations, and evaluating radioactive iodine uptake and scans. Tests to measure circulating thyroid hormone concentrations can include total thyroxine (T4), total triiodothyronine (T3), free thyroxine index, free T4 (FT4), and free T3 (FT3).
Total T4 and total T3 measurements are less accurate because several medications can interfere (for example, estrogen and estrogen-containing birth control pills..." 

"Anyone who has taken birth control pills, or estrogen, needs to keep in mind that one additional effect of that maneuver is to increase thyroid-binding proteins in the blood. This means that almost any thyroid blood test result is quite suspect, because the regular tests will show plenty of thyroid hormone in the bloodstream, but you may still not have sufficient thyroid hormone in the tissues. In other words, estrogens will make thyroid blood tests even more unreliable than they already are. What this means is that you can be told you don't have a thyroid problem when you really do.

"In addition, if you are taking thyroid medicine, you could be told that you're taking plenty, when in the reality of your tissue levels (not measured on blood tests) you need more. This is not a minor subtlety. It is of critical importance to you. A lack of proper thyroid hormone levels has been implicated in everything from bad PMS to irregular cycles, low libido, infertility, miscarriage, endometriosis, polycystic ovary, uterine fibroids, dysfunctional bleeding, severe menopause, and osteoporosis. With a long list of possible gynecological problems such as this, you are well advised to optimize your thyroid function as much as possible.

"So once again we return to a recurrent theme in our office & coaching practice: if there has been any thyroid, diabetes, migraine, colitis, rheumatoid or other autoimmune problems in your family, then you are likely to have some degree of thyroid involvement yourself. This is especially true approaching and during menopause years. The Journal of Epidemiology in 2001 had a compelling article revealing that as many as 26% of menopausal women were hypothyroid, making their menopause years worse.

"Therefore, you owe it to yourself to do extra diagnostic maneuvers for revealing low thyroid, such as obtaining thyroid antibody testing in addition the routine T3, T4, and TSH. In addition, make sure the T4 determination is the Free T4, and your T3 testing is for both Free T3 and Total T3. Consider asking for a clinical trial of thyroid medicine if you are in the low normal area on these results.
Perhaps even more important is for the person who is already diagnosed and being treated for low thyroid to make sure that your treatment protocol is optimal."

(Note: gonadotropins are used in infertility treatments)
"Increasing levels of E2 in gonadotropin-treated women stimulated hepatic synthesis of SHBG and TBG, and consequently increases in T4 concentration. Nevertheless, unchanged FTI and TSH suggested that a euthyroid state was maintained. The temporal patterns for the rise in serum concentrations of TBG and SHBG during gonadotropin therapy suggest that the synthesis of these proteins by the liver has different sensitivities to E2."