Testosterone therapy is also not recommended for patients with signs of benign prostatic hypertrophy (BPH) or prostate cancer. While it is now known that testosterone itself does not cause either of these, it is thought to have the potential to exacerbate the problem when already present. This may in fact be a result of local aromatase production in prostate tumors, which increases local conversion of testosterone to estradiol, which in turn stimulates tumor growth. Research now indicates a complex relationship between estrogens and androgens in the etiology of prostate cancer, while serum levels of individual endogenous sex hormones have been found to be unrelated to prostate cancer risk. Studies show that estrogens play both adverse and beneficial roles mediated by different types of estrogen receptor. Testosterone’s effects on the prostate are mediated by its more active metabolite, dihydrotestosterone (DHT), produced by the action of 5-alpha reductase type II (5-alpha reductase type I is the predominant form in the skin, and is responsible for the local action of DHT on hair follicles leading to the development of male pattern baldness). Prostate growth can be controlled by 5-alpha reductase inhibitors, and these may also have a role in prostate cancer prevention and treatment.
The Hormones Tested in our Male Profiles and Why
Estradiol is tested because too much of it, relative to testosterone levels, suppresses testosterone receptors in target tissues and eventually leads to feminizing effects in men, such as breast enlargement. In healthy young men, testosterone is at its highest level and estradiol is very low. However, as men age, this shifts to a higher estradiol/testosterone ratio. Even if testosterone levels are normal, symptoms can indicate functional testosterone deficiency because of the effects of higher than normal estradiol levels. There are several mechanisms by which relative levels of estradiol and testosterone can change. Weight gain, whether or not this results from low testosterone, results in increased production of aromatase in fat cells, which converts testosterone to estradiol. Rising estradiol levels also cause the liver to produce more SHBG, which has a greater affinity for testosterone than estradiol. This acts to suppress further the amount of circulating free testosterone. Estradiol also decreases luteinizing hormone (LH) production by negative feedback on the pituitary gland, which in turn acts to decrease testicular testosterone production. High estradiol levels can be controlled by weight reduction to decrease the amount of aromatase-producing adipose tissue. There are nutritional and pharmaceutical approaches to aromatase inhibition.
Progesterone is present in men but at a much lower level than found in premenopausal women. Some men supplement with topical progesterone to help with sleep, to support adrenal cortisol production (progesterone is a cortisol precursor), and to counterbalance the effects of estrogens on the prostate. It has also been used as a mild antiandrogen in patients with BPH and to reduce male pattern baldness, because of its competition with testosterone and DHT for androgen receptors. Salivary progesterone levels can, therefore, be useful to monitor supplementation.
Testosterone is the primary indicator of male hypogonadism and andropause. Many things can contribute to low testosterone levels, including high cortisol levels and high estrogen levels, as described above.Testosterone production in the testes is controlled by the hypothalamic-pituitary-testicular axis, and so dysfunctions of the hypothalamus or pituitary can affect levels, as well as the negative feedback effect of estradiol on LH levels to suppress testosterone production.
SHBG binds and transports both testosterone and estrogens in the bloodstream, and it therefore regulates the relative amounts of free and bound hormone and consequently their bioavailability to target tissues. SHBG is a protein produced by the liver in response to exposureto any type of estrogen. Testosterone binds about three times more tightly to SHBG than does estradiol, so this increase in SHBG as a result of estrogen exposure causes the relative proportion of bioavailable testosterone to estradiol to decrease even further, exacerbating the symptoms of testosterone deficiency. Many factors, in addition to estrogen exposure, can affect SHBG levels. Thyroid hormone increases SHBG production, whereas insulin, on the other hand, decreases SHBG levels. In young men, testosterone levels are usually high and SHBG low, making most of the testosterone bioavailable. However, as men age, gain weight, and their estrogen levels increase, SHBG also rises, decreasing bioavailable testosterone. Measuring SHBG in blood provides an indication of the overall exposure to estrogens, as well as the bioavailable (free) fraction of testosterone (calculated from the ratio of testosterone to SHBG).
PSA is a measure of prostate health and high levels can indicate the presence of BPH or advancing prostate cancer. As prostate cells start to become crowded, they produce PSA, which acts to suppress angiogenesis and therefore reduce the blood supply to the surrounding tissue to prevent it from further growth. High levels are therefore seen only as a result of growth that is fairly rapid. It is important to test PSA levels prior to starting testosterone therapy, as a sharp increase in PSA can indicate prostate problems.
DHEA is a precursor for the production of estrogens and testosterone, and is therefore normally present in greater quantities than all the other steroid hormones. It is mostly found in the circulation in its conjugated form, DHEA sulfate (DHEA-S). Its production, which occurs in the adrenal glands, declines gradually with age. Like cortisol, it is involved with immune function and a balance between the two is essential. Low DHEA can result in reduced libido and general malaise.
Cortisol is an indicator of adrenal function and exposure to stressors. Under normal circumstances, adrenal cortisol production shows a diurnal variation and is highest early in the morning, soon after waking, falling to lower levels in the evening. Normal cortisol production shows a healthy ability to respond to stress. Low cortisol levels can indicate adrenal fatigue (a reduced ability to respond to stressors), and can leave the body more vulnerable to poor blood sugar regulation and immune system dysfunction. Chronically high cortisol is a consequence of high, constant exposure to stressors, and this has serious implications for long-term health including an increased risk of cancer, osteoporosis, and possibly Alzheimer’s disease10. Free T4, free T3, TSH, and TPO tests can can indicate the presence of an imbalance in thyroid function, which can cause a wide variety of symptoms, including feeling cold all the time, low stamina, fatigue (particularly in the evening), depression, low sex drive, weight gain, and high cholesterol.