Hypothyroidism affects women seven times more frequently than men. The epidemic of estrogen dominance among women is likely at the core of this disparity. Excess estrogen levels or “estrogen dominance” causes the liver to produce high levels of thyroid binding globulin (TBG), which, as its name suggests, binds the thyroid hormone and decreases the amount of thyroid hormone that can be assimilated and utilized by the cells.
Women with estrogen dominance may have a normally functioning thyroid gland that produces adequate amounts of thyroid hormone, however, because the hormone is inactivate when bound to TBG, little functional action is available at a cellular level and symptoms can present as if clinical hypothyroidism was present. Moreover, symptoms of hypothyroidism and estrogen dominance often overlap with weight gain, fatigue, low libido, hair loss, difficult cognition, low mood and irregular menstruation.
Estrogen Dominance Made Worse
Hormonal contraception, pregnancy, and synthetic estrogens prescribed during and after menopause exacerbate estrogen dominance and increase levels of TBG. It is also important to remember the exacerbation of estrogen dominance in hypothyroidism. Estrogen must first be made water soluble by the liver in order to be eliminated from the body. Hypothyroidism hinders the effectiveness of this this elimination pathway through the liver. This results in a buildup of proliferative estrogen, increasing risk of pathologies such as breast cancer, uterine fibroids and ovarian cysts.
To further illustrate the connection between estrogen dominance and low thyroid function, consider polycystic ovary syndrome (PCOS), a metabolic disorder often resulting in anovulatory cycles and estrogen dominance. Progesterone is a hormone produced by the corpus luteum upon ovulation and functions to balance the effects of estrogen. Anovulation results in insufficient progesterone production and therefore, ongoing estrogen dominance. Endocrine Research published a study which found that Hashimoto’s thyroiditis, clinical hypothyroidism of an autoimmune nature, is highly prevalent among women with PCOS. They concluded that “Increased estrogen and the estrogen/progesterone ratio seem to be directly involved in high anti-TPO levels in PCOS patients.”
A study published in Molecular Cellular Endocrinology revealed 2- Methoxy estradiol, an endogenous estrogen metabolite “induced dramatic changes in (thyroid) cell morphology and decreased the viability of the cells, as well as disrupted the structural integrity of cultured thyroid follicles.” They found that this process results in the release of thyroid antigens that may play a role in high incidence of thyroid autoantibodies and autoimmune thyroid disease in women.
Estrogen Replacement Therapy
Yet another study correlating estrogen dominance and hypothyroidism from the journal Thyroid, found that oral estrogen therapy increases thyroxine dosage requirements in hypothyroid women, due to increased TBG and subsequent lower levels of free thyroxine. On a positive note, transdermal estrogen therapy was not found to affect TBG levels and therefore may be the preferred therapy for postmenopausal women who require concomitant treatment with estrogen and thyroid replacement.
To contrast the effect of estrogen on thyroid hormone, progesterone decreases TBG and increases the activity of thyroid hormones when present in adequate levels. Thyroid hormones, like progesterone, have a thermogenic effect on the body, accelerating metabolism and utilizing fat for energy production. The Journal of Endocrinology featured a study showing triiodothyronine (T3) significantly stimulated the release of progesterone from luteal cells. Furthermore, research published in Clinical Endocrinology concluded that progesterone therapy increases free thyroxine (T4). Additionally, progesterone exhibits anti-inflammatory effects, regulates blood pressure, protects bone health, improves mood and reduces anxiety, supports fertility, and aids weight loss.
Though the thyroid is a small, butterfly-shaped gland, its impact on the body is anything but minute and delicate. When treating patients for hormonal imbalances, it is imperative to understand the complex interplay between thyroid hormones and sex hormones. The research summarized in this article illustrates that improving the issues of estrogen dominance by decreasing excess estrogen levels and by supporting healthy progesterone levels, will also provide benefits for thyroid hormones.
Arduc A, Aycicek dogan B, Bilmez S, et al. High prevalence of Hashimoto’s thyroiditis in patients with polycystic ovary syndrome: does the imbalance between estradiol and progesterone play a role?. Endocr Res. 2015;40(4):204-10.
Badawy A, State O, Sherief S. Can thyroid dysfunction explicate severe menopausal symptoms?. J Obstet Gynaecol. 2007;27(5):503-5.
Ben-rafael Z, Struass JF, Arendash-durand B, Mastroianni L, Flickinger GL. Changes in thyroid function tests and sex hormone binding globulin associated with treatment by gonadotropin. Fertil Steril. 1987;48(2):318-20.
Datta M, Roy P, Banerjee J, Bhattacharya S. Thyroid hormone stimulates progesterone release from human luteal cells by generating a proteinaceous factor. J Endocrinol. 1998;158(3):319-25.
Garelli S, Masiero S, Plebani M, et al. High prevalence of chronic thyroiditis in patients with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2013;169(2):248-51.
Kachuei M, Jafari F, Kachuei A, Keshteli AH. Prevalence of autoimmune thyroiditis in patients with polycystic ovary syndrome. Arch Gynecol Obstet. 2012;285(3):853-6
Kitamura S, Jinno N, Suzuki T, et al. Thyroid hormone-like and estrogenic activity of hydroxylated PCBs in cell culture. Toxicology. 2005;208(3):377-87.
Mazer NA. Interaction of estrogen therapy and thyroid hormone replacement in postmenopausal women. Thyroid. 2004;14 Suppl 1:S27-34.
Sathi P, Kalyan S, Hitchcock CL, Pudek M, Prior JC. Progesterone therapy increases free thyroxine levels–data from a randomized placebo-controlled 12-week hot flush trial. Clin Endocrinol (Oxf). 2013;79(2):282-7.
Wang SH, Myc A, Koenig RJ, Bretz JD, Arscott PL, Baker JR. 2-Methoxyestradiol, an endogenous estrogen metabolite, induces thyroid cell apoptosis. Mol Cell Endocrinol. 2000;165(1-2):163-72.