Testosterone and the cardiovascular system

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Testosterone and the cardiovascular system are the effects that the male hormone testosterone has on the cardiovascular system.

Contents

The predominant androgen in men, testosterone, has shown to substantially decline throughout the aging process. [1] [2] The decline in both serum and total testosterone with age have been linked to several disease states in men. [1] [3] [4] In particular, cardiac failure and ischemic heart disease have been linked to this natural biochemical decline in testosterone. [5] [6] [7] Previously, the higher cardiovascular risk in men has been attributed in part to the negative effects of systemic testosterone, however, more recent research has highlighted the protective nature of testosterone against cardiovascular disease. [5] The magnitude and mechanism of action by which low testosterone in men is influential in the pathogenesis of cardiovascular risk and the potential benefits of testosterone therapy has yet to be fully determined. [1]

Systemic effects

Low testosterone is associated with an increased risk for coronary artery disease through the promotion of a pro-atherosclerotic environment. [5] [8] [9] Some research has identified testosterone as a vasodilator and an endothelium-repairing hormone within many regions in the body, including the coronary arteries. [10] [11] Recent research depicts testosterone as important in decreasing the production of inflammatory cytokines such as tumor necrosis factor alpha, interleukin-1beta and interleukin-6, which are influential in atherosclerotic profiles. [10] [12] Although it is believed that the reduction in inflammatory cytokines is related to a decreased atherosclerotic profile, the full explanation of this mechanism requires further research. [12] [13]

Testosterone has also shown to be effective as an anti-atherosclerotic through preventing aortic cholesterol deposition in both rabbits fed high cholesterol diets and mice with low-density lipoprotein gene knockout. [10] [14] Fatty deposition within the aorta associated with low endogenous testosterone has been determined to be independent of the androgen receptor. [10] Although the mechanism has yet to be fully determined, aromatase activity and the activation of estrogen receptor alpha is partially responsible for the atherosclerotic profile characteristic of low testosterone. [10]

Decreased systemic testosterone in men has also been reported in men with heart failure, whereby the severity of the disease is proportional to the reduction in systemic testosterone levels. [5] Although a direct mechanism of action is not fully understood, some research attribute low testosterone to advancing side effects of heart failure, such as decreased exercise ability, decreased muscle mass, fatigue/dyspnea and cachexia. [5]

Replacement therapy

Physiological testosterone is crucial for normal functionality in men. Long-term administration of physiological testosterone in mouse models has shown to be atheroprotective by increasing the HDL portion of cholesterol (the anti-atherosclerotic cholesterol). [10] [15] The beneficial action of testosterone in elevating the HDL fraction can be attributed to its conversion via aromatase activity in adipose tissue into 17-beta estradiol and its subsequent activation of estrogen alpha-receptors; thus, more testosterone leads to greater conversion into estrogen and thus a healthier lipid profile. [10] This understanding has been determined in several studies, although results of these studies are contradictory. [10] [16] [17]

Testosterone replacement therapy in men diagnosed with pre-existing heart disease has been related to an increased risk of myocardial infarction. [18] Furthermore, recent research has linked testosterone replacement therapy to an increase in deaths and other cardiovascular occurrences in men whom document a history of coronary artery disease. [19] Further research is required to determine the full extent to which testosterone replacement therapy in aging men plays a role in the risk and/or advantage of cardiovascular occurrences. [20]

However, when given to men with hypogonadism in the short- and medium-term, testosterone replacement therapy does not increase the risk of cardiovascular events (including strokes and heart attacks and other heart diseases). The long-term safety of the therapy for this condition is not known yet. [21] [22]

Related Research Articles

High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle. HDL particles enlarge while circulating in the blood, aggregating more fat molecules and transporting up to hundreds of fat molecules per particle.

<span class="mw-page-title-main">Estrogen</span> Primary female sex hormones

Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Estradiol, an estrane, is the most potent and prevalent. Another estrogen called estetrol (E4) is produced only during pregnancy.

<span class="mw-page-title-main">Testosterone</span> Primary male sex hormone

Testosterone is the primary male sex hormone and androgen in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair. It is associated with increased aggression, sex drive, the inclination to impress partners and other courting behaviors. In addition, testosterone in both sexes is involved in health and well-being, where it has a significant effect on overall mood, cognition, social and sexual behavior, metabolism and energy output, the cardiovascular system, and in the prevention of osteoporosis. Insufficient levels of testosterone in men may lead to abnormalities including frailty, accumulation of adipose fat tissue within the body, anxiety and depression, sexual performance issues, and bone loss.

<span class="mw-page-title-main">Atherosclerosis</span> Form of arteriosclerosis

Atherosclerosis is a pattern of the disease arteriosclerosis, characterized by development of abnormalities called lesions in walls of arteries. These lesions may lead to narrowing of the arteries' walls due to buildup of atheromatous plaques. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. In severe cases, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney disorders, depending on which body parts(s) the affected arteries are located in the body.

<span class="mw-page-title-main">Estradiol</span> Chemical compound

Estradiol (E2), also spelled oestradiol, is an estrogen steroid hormone and the major female sex hormone. It is involved in the regulation of the estrous and menstrual female reproductive cycles. Estradiol is responsible for the development of female secondary sexual characteristics such as the breasts, widening of the hips and a female-associated pattern of fat distribution. It is also important in the development and maintenance of female reproductive tissues such as the mammary glands, uterus and vagina during puberty, adulthood and pregnancy. It also has important effects in many other tissues including bone, fat, skin, liver, and the brain.

<span class="mw-page-title-main">Hypercholesterolemia</span> High levels of cholesterol in the blood

Hypercholesterolemia, also called high cholesterol, is the presence of high levels of cholesterol in the blood. It is a form of hyperlipidemia, hyperlipoproteinemia, and dyslipidemia.

Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids or lipoproteins in the blood. Dyslipidemia is a risk factor for the development of atherosclerotic cardiovascular diseases (ASCVD), which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Although dyslipidemia is a risk factor for ASCVD, abnormal levels don't mean that lipid lowering agents need to be started. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia. Likewise, increased levels of O-GlcNAc transferase (OGT) may cause dyslipidemia.

<span class="mw-page-title-main">Ethinylestradiol</span> Estrogen medication

Ethinylestradiol (EE) is an estrogen medication which is used widely in birth control pills in combination with progestins. In the past, EE was widely used for various indications such as the treatment of menopausal symptoms, gynecological disorders, and certain hormone-sensitive cancers. It is usually taken by mouth but is also used as a patch and vaginal ring.

Hypoestrogenism, or estrogen deficiency, refers to a lower than normal level of estrogen. It is an umbrella term used to describe estrogen deficiency in various conditions. Estrogen deficiency is also associated with an increased risk of cardiovascular disease, and has been linked to diseases like urinary tract infections and osteoporosis.

<span class="mw-page-title-main">Testosterone enanthate</span> Chemical compound

Testosterone enanthate is an androgen and anabolic steroid (AAS) medication which is used mainly in the treatment of low testosterone levels in men. It is also used in hormone therapy for transgender men. It is given by injection into muscle or subcutaneously usually once every one to four weeks.

Androgen replacement therapy (ART), often referred to as testosterone replacement therapy (TRT), is a form of hormone therapy in which androgens, often testosterone, are supplemented or replaced. It typically involves the administration of testosterone through injections, skin creams, patches, gels, pills, or subcutaneous pellets. ART is often prescribed to counter the effects of male hypogonadism.

Masculinizing hormone therapy, also known as transmasculine hormone therapy, or female-to-male hormone therapy, is a form of hormone therapy and gender affirming therapy which is used to change the secondary sexual characteristics of transgender people from feminine or androgynous to masculine. It is a common type of transgender hormone therapy, and is predominantly used to treat transgender men and other transmasculine individuals. Some intersex people also receive this form of therapy, either starting in childhood to confirm the assigned sex or later if the assignment proves to be incorrect.

Feminizing hormone therapy, also known as transfeminine hormone therapy, is hormone therapy and sex reassignment therapy to change the secondary sex characteristics of transgender people from masculine or androgynous to feminine. It is a common type of transgender hormone therapy and is used to treat transgender women and non-binary transfeminine individuals. Some, in particular intersex people but also some non-transgender people, take this form of therapy according to their personal needs and preferences.

Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. These symptoms can include hot flashes, vaginal atrophy, accelerated skin aging, vaginal dryness, decreased muscle mass, sexual dysfunction, and bone loss or osteoporosis. They are in large part related to the diminished levels of sex hormones that occur during menopause.

Roger W. Robinson was an American cardiologist who served as chief of cardiology and chief of medicine at Memorial Hospital, Worcester, MA. He was the director of the Lipid Research Laboratory and served as a professor at the University of Massachusetts Medical School. He is considered a pioneer in the field of lipid and atherosclerosis research.

<span class="mw-page-title-main">Testosterone (medication)</span> Medication and naturally occurring steroid hormone

Testosterone (T) is a medication and naturally occurring steroid hormone. It is used to treat male hypogonadism, gender dysphoria, and certain types of breast cancer. It may also be used to increase athletic ability in the form of doping. It is unclear if the use of testosterone for low levels due to aging is beneficial or harmful. Testosterone can be used as a gel or patch that is applied to the skin, injection into a muscle, tablet that is placed in the cheek, or tablet that is taken by mouth.

Remnant cholesterol, also known as remnant lipoprotein, is a very atherogenic lipoprotein composed primarily of very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL). Stated another way, remnant cholesterol is all plasma cholesterol that is not LDL cholesterol or HDL cholesterol, which are triglyceride-poor lipoproteins. However, remnant cholesterol is primarily chylomicron and VLDL, and each remnant particle contains about 40 times more cholesterol than LDL.

<span class="mw-page-title-main">Estrogen (medication)</span> Type of medication

An estrogen (E) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy, and as part of feminizing hormone therapy for transgender women. They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens. They are available in a wide variety of formulations and for use by many different routes of administration. Examples of estrogens include bioidentical estradiol, natural conjugated estrogens, synthetic steroidal estrogens like ethinylestradiol, and synthetic nonsteroidal estrogens like diethylstilbestrol. Estrogens are one of three types of sex hormone agonists, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone.

The pharmacology of estradiol, an estrogen medication and naturally occurring steroid hormone, concerns its pharmacodynamics, pharmacokinetics, and various routes of administration.

The BaleDoneen Method is a risk assessment and treatment protocol aimed at preventing heart attack and stroke. The method also seeks to prevent or reduce the effects of type 2 diabetes. The method was developed by Bradley Field Bale and Amy Doneen.

References

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  3. ↑ Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR (February 2001). "Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging". The Journal of Clinical Endocrinology and Metabolism. 86 (2): 724–731. doi: 10.1210/jcem.86.2.7219 . PMID   11158037.
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  8. ↑ Nettleship JE, Jones TH, Channer KS, Jones RD (November 2007). "Physiological testosterone replacement therapy attenuates fatty streak formation and improves high-density lipoprotein cholesterol in the Tfm mouse: an effect that is independent of the classic androgen receptor". Circulation. 116 (21): 2427–2434. doi: 10.1161/CIRCULATIONAHA.107.708768 . PMID   17984376.
  9. ↑ Joint Meeting of the Bone, Reproductive and Urologic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee (17 September 2014). "Nonclinical Effects of Testosterone on the Cardiovascular System" (PDF). FDA Briefing Document. U.S. Food and Drug Administration. Archived from the original (PDF) on 11 March 2016.
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  11. ↑ Webb CM, McNeill JG, Hayward CS, de Zeigler D, Collins P (October 1999). "Effects of testosterone on coronary vasomotor regulation in men with coronary heart disease". Circulation. 100 (16): 1690–1696. doi: 10.1161/01.cir.100.16.1690 . PMID   10525487.
  12. 1 2 Corrales JJ, Almeida M, Burgo R, Mories MT, Miralles JM, Orfao A (June 2006). "Androgen-replacement therapy depresses the ex vivo production of inflammatory cytokines by circulating antigen-presenting cells in aging type-2 diabetic men with partial androgen deficiency". The Journal of Endocrinology. 189 (3): 595–604. doi: 10.1677/joe.1.06779 . PMID   16731790.
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  14. ↑ Nathan L, Shi W, Dinh H, Mukherjee TK, Wang X, Lusis AJ, Chaudhuri G (March 2001). "Testosterone inhibits early atherogenesis by conversion to estradiol: critical role of aromatase". Proceedings of the National Academy of Sciences of the United States of America. 98 (6): 3589–3593. Bibcode:2001PNAS...98.3589N. doi: 10.1073/pnas.051003698 . JSTOR   3055279. PMC   30697 . PMID   11248122.
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  19. ↑ Vigen R, O'Donnell CI, Barón AE, Grunwald GK, Maddox TM, Bradley SM, et al. (November 2013). "Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels". JAMA. 310 (17): 1829–1836. doi:10.1001/jama.2013.280386. PMID   24193080.
  20. ↑ "The risk of Cardiovascular Events in Men Receiving Testosterone Therapy: An Endocrine Society Statement" (PDF). Endocrine Society. February 7, 2014.
  21. ↑ "Research provides reassurance about the safety of testosterone treatment". NIHR Evidence (Plain English summary). National Institute for Health and Care Research. 6 February 2023. doi:10.3310/nihrevidence_56696. S2CID   257851823.
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