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The Effects of Hyperthyroidism on Testosterone Levels
by: Karl Hoffman

In an earlier article in Mind & Muscle we discussed the widespread use of thyroid hormone (T4 and T3) for weight loss by bodybuilders. As studies have shown that the use of these hormones (henceforth we will simply call them both T3, since this is the most common agent used for fat loss) leads to a loss of muscle mass as well as fat mass, bodybuilders are generally advised to use an anabolic steroid or prohormone along with T3 to spare muscle mass. Is this catabolic effect of T3 on muscle simply due to an increase in metabolic rate, or do T3 use and naturally occurring hyperthyroidism actually lower testosterone levels, contributing to muscle loss? The question is more than academic. If muscle loss due to hyperthyroidism is unrelated to changes in testosterone, then there is no need for concern about complications resulting from depressed testosterone, such as gynecomastia and sexual dysfunction. On the other hand, if T3 use actually lowers testosterone levels, this would provide even greater incentive to use testosterone or an anabolic steroid/prohormone when using T3.

In this article I would like to review the research that has examined what if any effects both exogenous T3 use and natural hyperthyroidism have on testosterone levels. As with the existing research in other areas, we will see conflicting studies, but nevertheless will come away with a coherent picture of how T3 affects circulating testosterone. Before delving into the literature, a brief review of how testosterone is transported through the bloodstream is in order. This will help us greatly later.

Transport of Testosterone in the Circulation

Since testosterone is relatively insoluble in water (and hence blood) it travels through the circulatory system bound to proteins. The major binding protein, Sex Hormone Binding Protein (SHBG) is responsible for carrying between 60 – 70% of the body’s testosterone through the bloodstream. The testosterone that is bound to SHBG is bound so tightly that it is considered biologically inactive. Virtually all the remaining testosterone is bound loosely to a number of other binding proteins, the main one being albumin. Only about 2% of the body’s testosterone circulates free, or unbound. However, as mentioned, the testosterone that is albumin bound is only attached very loosely to this transport protein and so is able to interact with the androgen receptor as if it were free. Hence it, like free testosterone, is considered to be biologically active. The free and albumin bound testosterone together are called the bioactive or bioavailable fraction.

Factors Influencing the Synthesis of SHBG and Albumin

SHBG itself is produced in the liver, and its production is under the control of a number of factors, including androgen and estrogen levels, insulin, and thyroid hormone. For example, androgens lower levels of SHBG, while estrogens raise SHBG. Thyroid hormone has been shown in numerous studies to elevate levels of SHBG. Albumin synthesis, like that of SHBG, is also under the control of thyroid hormone. In cases of hyperthyroidism, albumin levels have been observed to be lower than in controls (1). To quantify the differences in SHBG and albumin in hyperthyroid patients versus controls, we can refer to the data presented in (1). There hyperthyroidism was characterized by SHBG and albumin levels of 187 nmol/l and 36.2 g/l respectively. SHBG and albumin in controls were 50.9 nmol/l and 43.5 g/l. So we see that hyperthyroidism increases SHBG levels while it decreases albumin.

Administration of synthetic T3 also leads to an increase in SHBG production. Lovejoy et al. looked at the effects of the administration of 50 mcg of synthetic T3 (Cytomel) on SHBG production in normal subjects over the course of 2 months (2). SHBG was observed to increase by 150%.

Relationship Between SHBG, Albumin, and Total Testosterone Levels

Numerous studies have shown that total testosterone (free+SHBG bound+albumin bound) correlates with SHBG levels. As SHBG levels rise, testosterone is believed to partition out of the free and albumin bound phases into the SHBG phase under the law of mass action. Testosterone bound tightly to SHBG is less subject to the action of metabolic enzymes. Hence the increase in SHBG bound testosterone leads to a decrease in the metabolic clearance rate of testosterone, with a corresponding increase in total plasma testosterone (1). So with decreased metabolic clearance of testosterone, we might anticipate that the elevated SHBG levels associated with natural and artificially induced hyperthyroidism would lead to an increase in total testosterone levels. In fact, this is exactly what is seen. For example, in the research by Lovejoy et al. cited above, a 42% increase in serum total testosterone was observed. In (1), which looked at testosterone levels in hyperthyroid females, the hyperthyroid patients had total T levels of 1.5 nmol/l vs. 1.0 nmol/l in controls. So the increase in total T is of the same magnitude irrespective of whether hyperthyroidism is natural or experimentally induced, and it is not gender specific. This phenomenon of elevated SHBG and total testosterone is seen almost universally in studies that have measured these parameters in hyperthyroidism.

Bioavailable Testosterone in Hyperthyroidism

So we have seen that by virtue of elevating SHBG levels, thyroid hormone raises total testosterone levels. But as discussed above, only the bioavailable fraction, that is free plus albumin bound T, is capable of interacting with the androgen receptor and hence is of physiological significance. The important question then is what are the effects of natural and experimentally induced hyperthyroidism on bioavailable T? We mentioned above that the increase in total T is due to testosterone leaving the bioavailable phase and entering the SHBG bound phase. This could have two possible outcomes as far as bioavailable T levels are concerned. One possibility is that the body senses the drop in bioavailable T and compensates for this drop by increasing the production of Luteinizing Hormone (LH) by the pituitary. LH as we know stimulates the testes to produce testosterone. So an increase in LH could restore bioavailable T levels to normal.

The other possibility is that the body fails to compensate for the drop in bioavailable T, with either no increase or an insufficient increase in LH production. It turns out the latter scenario, an uncompensated drop in bioavailable T, is what is most commonly seen in studies that have measured bioavailable T under conditions of hyperthyroidism.

For example, in the study (1) by Loric et al. hyperthyroid subjects had average non-SHBG-bound T levels of 0.097 nmol/l. After 3 to 6 months of treatment with the antithyroid drug carbimazol non-SHBG-bound T levels had increased to 0.196nml/l. Free T increased from 2.59 pmol/l to 3.74 pmol/l. Control subjects in this study had non-bound and free T levels of 0.152 nmol/l and 1.05 pmol/l, respectively.

In the second study we have discussed thus far, the one by Lovejoy et al. the authors did not measure any changes in total unbound T, only free T. A small drop in free T, from 142.8 +/- 18.4 to 137.3 +/- 19.5 pmol/L was observed, but the authors did not consider this statistically significant.

A study by Abalovich et al showed that in hyperthyroid males vs. a normal control group,

Mean basal LH was significantly higher than the control group (7.8 +/- 4.7 vs. 5.0 +/- 1.9 mIU/mL, respectively, p < 0.02), with hyperresponse to GnRH…Basal levels of steroids and SHBG were significantly higher in patients than in normal men (T: 9.3 +/- 3.3 vs. 5.4 +/- 1.6 ng/mL, p < 0.005; E2: 62.2 +/- 25.2 vs. 32.1 +/- 11.0 pg/mL, p < 0.005; 17-OHP: 2.4 +/- 0.9 vs. 1.1 +/- 0.5 ng/mL, p < 0.001; SHBG: 102.3 +/- 37.3 vs. 19.0 +/- 5.0 nmol/L, p < 0.01). Basal bioT was lower in patients than controls (1.7 +/- 0.8 and 3.1 +/- 1.9 ng/mL, p < 0.02). (3)

In the previously cited study be Abalovich et al. we see the body attempting to increase bioavailable T by increasing LH production, albeit unsuccessfully. The combination of elevated LH and low bioavailable T has prompted researchers to investigate whether testicular dysfunction (primary hypogonadism) is responsible for the muted testosterone secretion in response to elevated LH levels. Indeed this seems to be the case, at least in Grave’s disease (4). In this study Grave’s disease patients exhibited a reduced testosterone secretory response to an hCG (Human Chorionic Gonadotropin) challenge, suggesting some degree of testicular failure (primary hypogonadism). However, there is no existing research showing that direct exposure of adult human Leydig cells to thyroid hormone leads to any type of dysfunction; the evidence thus far is only circumstantial.

(Normally hCG acts like LH, eliciting a strong testosterone response in normal subjects. In hypogonadal subjects where the testes are malfunctioning hCG elicits only weak or no testosterone response. In patients suffering from secondary hypogonadism where the pituitary is secreting inadequate amounts of LH but the testes are functioning, hCG administration results in an increase in testosterone secretion.)

Additional Abnormalities of the Hypothalmic Pituitary Gonadal Axis in Hyperthyroidism

In addition to the rather well documented decrease in bioavailable testosterone associated with hyperthyroidism discussed above, several additional abnormalities in hypothalamic-pituitary -gonadal function have been recorded in the literature in cases of hyperthyroidism. Free estradiol levels have been observed to be elevated out of proportion to the rise in SHBG (5). The peripheral aromatization of androgens to estrogens has also been reported (6), as has increased levels of progesterone in both men and women with Grave’s disease (7). Elevated estradiol and depressed bioavailable testosterone have been cited as the cause of sexual dysfunction common in hyperthyroid individuals.

The elevated levels of estradiol and progesterone seen in hyperthyroidism undoubtedly contribute to the high incidence of gynecomastia in this disease. It has also been suggested that increased levels of androstenedione (8) and androstenediol (9) observed in cases of hyperthyroidism could also contribute to gynecomasta via their aromatization to estrogens.

A Medline search failed to turn up any evidence of experimentally induced gynecomastia upon T3 administration however, so it is not clear if this is a symptom of drug induced hyperthyroidism or a phenomenon associated uniquely with naturally occurring thyrotoxicosis. Considering though that many if not most T3 users will be supplementing with testosterone which will add to any potential T3 induced rise in estradiol, testosterone use could conceivably add to the likelihood of developing gynecomastia. It might be prudent for someone on a T3 cycle who is using testosterone to add tamoxifen or an aromatase inhibitor to lessen the chances of developing gynecomastia, or perhaps use a non-aromatizing steroid.


(1) Loric S, Duron F, Guechot J, Aubert P, Giboudeau J. Testosterone and its binding in hyperthyroid women before and under antithyroid drug therapy. Acta Endocrinol (Copenh). 1989 Sep;121(3):443-6.

(2) Lovejoy JC, Smith SR, Bray GA, Veldhuis JD, Rood JC, Tulley R. Effects of experimentally induced mild hyperthyroidism on growth hormone and insulin secretion and sex steroid levels in healthy young men. Metabolism. 1997 Dec;46(12):1424-8

(3) Abalovich M, Levalle O, Hermes R, Scaglia H, Aranda C, Zylbersztein C, Oneto A, Aquilano D, Guti Hypothalamic-pituitary-testicular axis and seminal parameters in hyperthyroid males. Thyroid. 1999 Sep;9(9):857-63

(4) Velazquez EM, Bellabarba Arata G. Effects of thyroid status on pituitary gonadotropin and testicular reserve in men. Arch Androl. 1997 Jan-Feb;38(1):85-92.

(5) Chopra IJ, Tulchinsky D. Status of estrogen-androgen balance in hyperthyroid men with Graves’ disease. J Clin Endocrinol Metab. 1974 Feb;38(2):269-77.

(6) Southren AL, Olivo J, Gordon GG, Vittek J, Brener J, Rafii F. The conversion of androgens to estrogens in hyperthyroidism. J Clin Endocrinol Metab. 1974 Feb;38(2):207-14.

(7) Nomura K, Suzuki H, Saji M, Horiba N, Ujihara M, Tsushima T, Demura H, Shizume K. High serum progesterone in hyperthyroid men with Graves’ disease. J Clin Endocrinol Metab. 1988 Jan;66(1):230-2

(8) Ridgway EC, Maloof F, Longcope C. Androgen and oestrogen dynamics in hyperthyroidism. J Endocrinol. 1982 Oct;95(1):105-15

(9) Tagawa N, Takano T, Fukata S, Kuma K, Tada H, Izumi Y, Kobayashi Y, Amino N. Serum concentration of androstenediol and androstenediol sulfate in patients with hyperthyroidism and hypothyroidism. Endocr J. 2001 Jun;48(3):345-54.

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