Low testosterone (hypogonadism) can be caused by a variety of medical conditions and medications, but a few of these are even more likely to incite this condition. More specifically, hypogonadism and groups of symptoms similar to it are as readily caused by non-genetic conditions like diabetes and obesity, as genetically-based chromosomal abnormalities such as Klinefelter’s syndrome, Kallmann’s syndrome, Prader-Willi, and Myotonic dystrophy. Among medications, those most likely to cause low testosterone include statins (cholesterol medications), opiates (pain killers) and anti-depressants.
The condition of low testosterone falls into three basic categories of causes: 1) primary hypogonadism – originating from a problem in the testicles; 2) secondary hypogonadism – originating from a problem in the hypothalamus or the pituitary gland, the two parts of the brain that signal the testicles to produce testosterone; or 3) tertiary hypogonadism (sometimes called idiopathic or unknown) – originating from another internal condition or an external stimulus. Low testosterone causing medical conditions and medications are classified within this third and second category as their use leads to a reduction in pituitary derived hormones.
Diabetes is a condition that limits the body’s ability to produce enough insulin to properly control blood sugar levels. Insulin is the hormone responsible for transporting blood sugar (through the cell membrane) into the cells for use as fuel. When insulin is under-produced certain parts of the body can’t access available blood sugar and don’t get the necessary fuel for proper functioning.
Low testosterone is commonly associated with type 2 diabetes, and clinicians have been aware of the increased prevalence of low testosterone levels in patients with type 2 diabetes for several years. Using an amalgam of population-based studies, researchers Paresh Dandona and Sandeep Dhindsa examined this correlation, and in September of 2011 released a monumental study in Journal of Clinical Endocrinology and Metabolism. Their conclusions revealed hypergonadotropic hypogonadism was found in 25% of men with type 2 diabetes. It further reported that low testosterone concentrations in men with type 2 diabetes are associated with an increased prevalence of symptoms of hypogonadism, obesity, very high CRP concentrations, mild anemia, decreased BMD, and an increased (two to three times) risk of cardiovascular events and death in two small studies. Since the difference in testosterone levels between men with diabetes compared to men without diabetes is moderate, this correlation suggests that low testosterone levels can serve as an indicator for poor health, and possibly other chronic diseases. However, it should noted that which condition precedes the other is not completely clear (there is conflicting data here), or may not be a definite fact at all, but rather contingent upon other situational influencing variables.
Obesity is medically defined a condition that is characterized by excessive accumulation and storage of fat in the body, which is typically indicated by a body mass index of 30 or greater, i.e. the possession of a body fat percentage of 30% more. However, obesity is much more than just a mere cosmetic concern, as it increases the risk of health problems and diseases, such as heart disease, diabetes, hypertension, and low testosterone. The presence of high amounts of excess body fat overtaxes the body’s systems causing it to compensate in ways that promote strain, imbalances, and deficiencies. The latter two compensatory characteristics greatly contribute to the diminished testosterone secretion, which is closely linked to a reduction in metabolic function, and variety of other complications such as:
- Cancer, including cancer of the uterus, cervix, ovaries, breast, colon, rectum and prostate
- Gallbladder disease
- Erectile dysfunction and sexual health issues
- Nonalcoholic fatty liver disease
- Skin problems
- Sleep apnea
- Gynecologic problems, such as infertility and irregular periods
- High cholesterol and triglycerides
- Type 2 diabetes
- Metabolic syndrome, a combination of high blood sugar, high blood pressure, high triglycerides and high cholesterol
Fortunately modest weight loss, through the proper channels of dietary changes, exercise, and even prescriptions medications can improve and in most cases even reverse such obesity-related health problems.
Klinefelter syndrome, also known as the XXY condition, is a common genetic condition wherein males are born possessing an additional X chromosome within most of their cells. The usual male cell chromosome pattern is XY (containing one female ‘X’ chromosome and one male ‘Y’ chromosome), but males with Klinefelter syndrome possess the XXY pattern. So named after Dr. Henry Klinefelter the physician who first described a group of symptoms found in some men with this extra X chromosome. Although men with Klinefelter syndrome necessarily have the XXY pattern, not all of them display the negative associated symptoms. To differentiate between those Klinefelter syndrome males, who don’t display symptoms from those who do, the latter group is generally referred by the terms ‘XXY male’ or those with ‘XXY condition’.
Easily misdiagnosed as mere primary hypogonadism, Klinefelter syndrome actually encompasses this condition due to the presence of some of its more than 30 symptoms including adversely affected testicular growth that results in abnormally small testicles. This complication can, and often does, lead to reduced secretion of the testes produced primary male sex hormone testosterone. Klinefelter syndrome may also cause reduced muscle mass, little or no sperm production (impotency), reduced body and facial hair, and enlarged breast tissue (gynecomastia) all of which are indicative of low testosterone, and symptoms of hypogonadism. The effects of Klinefelter syndrome and many related (bearing hypogonadic symptoms) genetic disorders vary from person to person, i.e., not every carrier develops every symptom among which are:
- Asymptomatic; no symptoms at all
- Rounded body type
- Abnormal testicle development
- Low testosterone levels
- Reduced facial hair
- Reduced body hair
- Enlarged male breasts
- Small testes
- Inability to produce sperm
- Learning disabilities
- Speech difficulty
- Language development problems
- Reserved personality type; unassertive, quiet, sensitive
- Language impairment
- Delayed talking
- Difficulty reading
- Difficulty writing
Although Klinefelter syndrome is the most prevalent (1 out of 500 men) hypogonadic symptom producing genetic disorder, there are others such as:
- Kallmann’s syndrome – a recessive genetic disorder of the X chromosome occurring in approximately 1 out of 10,000 men, wherein a deficiency of (Gonadotropin-Releasing Hormone (GnRH) or) impairs the release of Luteinizing Hormone (LH) and Follicle-stimulating hormone (FSH), which decreases testosterone production.
- Prader-Willi syndrome – a genetic disorder that in infancy causes decreased muscle tone, and has a high rate of undescended testicles and underdeveloped genitals, and of course low testosterone levels. Prader-Willi is also characterized by an odd obsession with food (especially in early childhood), which often results in compulsive eating.
- Myotonic dystrophy – the most prevalent adult form of muscular dystrophy, is carried on the male ‘Y’ chromosome and usually results in testicular failure between 30 and 40 years of age.
Several other conditions also serve as causes of tertiary (third category) hypogonadism including orchitis an inflammatory condition of one or both testicles in males, generally caused by a bacterial or viral infection such as the mumps virus, and other such as chronic illnesses, cardiovascular problems, cirrhosis, alcoholism, etc.
Statins are a class of cholesterol lowering drugs that work by reducing the liver’s production of cholesterol. Statins effectively block the hydroxy-methylglutaryl-coenzyme a reductase (HMG-CoA reductase) enzyme in the liver that is responsible for making cholesterol. The other source of cholesterol within the bloodstream is dietary cholesterol, and although critical to the normal function of every bodily cell, too much of this waxy substance readily contributes to the development of atherosclerosis, a condition in which cholesterol-containing plaque forms on the arterial walls reducing and potentially blocking the flow of blood in the form of a clot, which if significant enough can result in chest pain (angina), heart attacks, and strokes.
A side effect of statin therapy, prescribed to lower cholesterol, is the apparent lowering of testosterone production. According to Giovanni Corona, MD, PHD, and researcher at the University of Florence in Italy, his new 3,500 male subject study of erectile dysfunction (ED) sufferers found that statin therapy patients were twice as likely to have increased prevalence of hypogonadism. This information coupled with the Center for Disease Control (CDC) statistic that about one of six adults in the U.S. has high cholesterol, along the Federal Agency for Healthcare Research and Quality (AHRQ) statistic that spending on statins increased 156 percent between 2000 and 2005 (15.8 million people to 29.7 million) nearly a decade ago, answers a lot of questions surrounding the increase in low testosterone sufferers.
Antidepressants are a group of Food and Drug Administration (FDA) approved medications which do precisely what their name implies, i.e. reduce depression, by affecting neurotransmitters (chemical messengers) that communicate between brain cells. In people with depression, the brain is incapable of using certain brain chemicals properly. Most antidepressants work by changing the brain’s chemical balance to make brain cells more available.
Antidepressant medications fall into four different classes of drugs:
- Monoamine oxidase inhibitors (MAOIs)
- Tricyclic antidepressants
- Serotonin reuptake inhibitors (SSRIs)
- Atypical antidepressants
The oldest class MAOIs including Parnate, Emsam, and Nardil are prone to interactions with certain foods, drinks, and medications, which is why they are not generally selected as a primary depression treatment. Also belonging to older versions of antidepressants is the class called tricyclics, among which are Norpramin, Vivactil, and Tofranil. Tricyclics work by inhibiting the brain’s reuptake of norepinephrine and serotonin partially inhibiting the brain’s reabsorption of the important neurotransmitter dopamine. However, tricyclics take approximately two weeks to become effective, cause withdrawal symptoms when abruptly discontinued, and tend to cause more side effects than the other classes of antidepressants including arrhythmia (abnormal heart rhythm). A third class of antidepressants, SSRIs, represents a newer version of this medication and includes Zoloft, Paxil, Prozac, and Lexapro. Acting directly on the brain chemical serotonin, SSRIs are preferred over older classes of antidepressants because of their less severe side effects. The last class of antidepressants, atypical antidepressants like Cymbalta, Wellbutrin, and Effexor are also newer. Atypical antidepressants target other neurotransmitters either alone or in addition to serotonin. For example, Effexor and Cymbalta affect both serotonin but also impact norepinephrine. From yet another angle, Wellbutrin impacts serotonin, but also blocks the reabsorption of the neurotransmitters norepinephrine and dopamine.
Although exceedingly efficient at their intended goals, each class of antidepressant possesses a substantial list of potential side effects, all of which include the following hypogonadic symptoms: erectile dysfunction; loss of libido (decreased sex drive); insomnia; anxiety; fatigue; and increased risk of bone fracture. It is for this reason that antidepressants are found among tertiary hypogonadism causing medications.
- Low Testosterone (Low-T)
- Medical Author:
- Charles Patrick Davis, MD, PhD
- Hypogonadotropic Hypogonadism in Type 2 Diabetes and Obesity
- J Clin Endocrinol Metab. 2011 September; 96(9): 2643–2651.
- Paresh Dandonaand Sandeep Dhindsa
- John Muir Health
- Cunningham GR, Matsumoto AM, Swerdloff R, eds. Low Testosterone and Men’s Health (pdf brochure). The Hormone Foundation Web site. http://www.hormone.org/Other/upload/low-testosterone-and-mens-health-bilingual-042710.pdf. Updated March 2010. Accessed October 5, 2011.
- Male hypogonadsim. Mayo Clinic Web site.
- Updated December 9, 2010. Accessed October 5, 2011.
- X-Plain: Low Testosterone Reference Summary. The Patient Education Institute. National Institutes of Health Web site. http://www.nlm.nih.gov/medlineplus/tutorials/lowtestosterone/ur189102.pdf. Updated April 2, 2009. Accessed October 5, 2011.
- Statins and Low Testosterone
- Giovanni Corona, MD, PHD,
- University of Florence in Italy
- What Causes Low Testosterone?
- Advanced Urological Care, P.C.
- J. Francois Eid, M.D. | 435 East 63rd Street New York, NY 10065
- Spyros Mezitis, MD, PhD, endocrinologist, Lenox Hill Hospital, New York.
- Jason Hedges, MD, PhD, urologist, Oregon Health and Science University, Portland, Ore.
- The Hormone Foundation: “Low Testosterone and Men’s Health.”
- The Hormone Foundation: “Patient Guide to Androgen Deficiency Syndromes in Adult Men.”
- Patient Education Institute: “Low Testosterone Reference Summary.”
- Pharmacy Author:
- Omudhome Ogbru, PharmD
- Statins: Are these cholesterol-lowering drugs right for you?
- Find out whether your risk factors for heart disease make you a good candidate for statin therapy.
- By Mayo Clinic staff
- Types of Antidepressants and Their Side Effects
- Melinda Smith, M.A., and Jeanne Segal, Ph.D. Last updated: August 2013.
- Antidepressants affect brain chemicals to ease depression symptoms. Explore their side effects and whether one of these antidepressants may be a good choice for you.
- Mayo Clinic
- Mayo Clinic Staff