Testosterone synthesis is a complex biological process, which involves many different anatomical structures and precursor hormones to occur. Problems with the functioning of these hormonal processes can cause fluctuations in T levels that can trigger an array of unpleasant side effects. Many men find success with testosterone replacement therapy (TRT) for the treatment of low T symptoms.
How Testosterone Works
Testosterone is the source of many bodily changes during our lifetime, in males its responsible for the onset of puberty, sperm production, and hair growth. Male sex hormones and their metabolites bind to androgen (AR) receptors, where they trigger the genetic transcription of the DNA. The “instructions” within the DNA cause changes to the body depending on the individual and their hormone levels.
Androgen receptors are located all over the body, including in your hair follicles and muscle cells. Hormone metabolites such as dihydrotestosterone and estradiol also work in this complex hormonal symphony. But they can also block the action of testosterone if they replace T molecules within AR receptors since they tend to bind more easily.
How Testosterone is Synthesized
To understand testosterone’s biological action, we first must understand how our body synthesizes androgens. The hypothalamus emits gonadotropin-releasing hormone (GnRH), which acts on the pituitary gland causing the secretion two hormones: luteinizing hormone (LH) and follicle stimulating hormone (FSH)–two of the key hormones in sperm production.
Inside the testis, Leydig cells surrounding the seminiferous tubules, are targeted by LH molecules to trigger the production of Pregnenolone. Pregnenolone is produced by the adrenal gland and is a precursor to both male and female sex hormones, as well as steroidal hormones.
Pregnenolone is then transformed into dehydroepiandrosterone (DHEA) by enzymes of the hydroxylase. Due to the catalyst actions of 3β-HSD and 17β-HSD in the Leydig cells, DHEA converts to testosterone; from there testosterone can be converted into DHT or estradiol via enzymatic activity in specific tissues.
Testosterone Synthesis and Aging
A slight decrease in T levels is to be expected as men age, but some research suggests that it’s not unusual for levels to fall 1-2% each year after age thirty. There is evidence that this decrease in levels isn’t entirely age-dependent, with one study finding that the average T levels of the male population have declined in the last 30 years.
The Journal of the International Society for the Study of the Aging Male defines hypogonadism as, “a condition in which the endogenous secretion of testosterone is either insufficient or inadequate to maintain serum testosterone levels within (the) normal range.” This condition can have a variety of implications depending on their sensitivity to hormone fluctuations. Some men with low T production only notice a minor decrease in stamina, whereas others with similar levels experience more severe side effects like osteoporosis and anemia.
Age-related hypogonadism was once thought to be a disorder only caused by testicular dysfunction, but newer studies are finding that problems with the hypothalamus and pituitary glands can also be a culprit. Primary hypogonadism is categorized by damaged Leydig cells in the testes, causing a condition called testicular failure.
Secondary hypogonadism, on the other hand, is caused by a malfunction of the hypothalamic-pituitary axis; one of the main causes of this is the decrease in secretions of GnRH and LH that accompanies aging.
Additionally, older men seem to be more sensitive to hormonal changes than younger men, though scientists still aren’t sure why that is. Older hypogonadal males also seem to experience more frequent and more severe side effects, as well.
What Happens When Testosterone Synthesis is Disrupted?
While aging is often a factor, it isn’t the only cause of testosterone synthesis disturbances. External factors such as exposure to certain chemicals like pesticides and fertilizers can also cause disturbances in T synthesis; these chemicals are sometimes referred to as endocrine disruptors, due to their ability to bind to receptors and disrupt hormone synthesis.
Ibuprofen, an anti-inflammatory medication that can be bought over-the-counter at any pharmacy or supermarket, has been shown to decrease testosterone synthesis, inhibit the actions of Leydig cells, and negatively impact enzymatic activity. The decrease in testosterone caused by ibuprofen usually goes unnoticed since the body offsets the deficit by ramping up the production of luteinizing hormone and thus maintaining homeostasis.
In the case of secondary hypogonadism, the decrease of GnRH and LH are a direct cause of low T, since these two hormones play such a vital role in its synthesis.
How Testosterone Replacement Therapy (TRT) Can Help
Since TRT bypasses your body’s production mechanisms, its proven to be an effective treatment for primary and secondary hypogonadism. Supplemental doses of TRT can decrease, and in some cases, even reverse side effects of low T.
A study on bedridden elderly men found that TRT substantially increased “vigor and ambulation.” The 2015 European Association of Urology guidelines recognizes TRT as an effective treatment for the symptoms of low T and states that it can positively impact BMI and sexual functioning.
Results vary, but some TRT patients report an improvement of symptoms in as little as a month. Hormone therapy is a medical procedure, so it should only be taken under a doctor’s supervision.
About Renew Vitality
Renew Vitality is changing the way people think about hormone therapy. Our physicians believe that treating low T requires a multi-faceted approach that involves changing lifestyle factors in addition to medications.
Our providers have decades of experience working in the endocrinological medicine and stay up to date with the newest advancements in hormonal health. Besides testosterone therapy, we also provide lesser-known treatments such as sermorelin therapy to treat adult-onset growth hormone deficiency.
If you’ve noticed changes in your body and think that decreased T production may be to blame, we encourage you to schedule a consultation. Our physicians will perform an exam and review your bloodwork to determine if low T is contributing to your symptoms. Once a diagnosis is made, we’ll work with you to find the right hormone therapy and wellness plan to help you reclaim your vitality.
This content was reviewed by Dr. Gary Kawesch. Dr. Kawesch graduated from Yale University, getting his degree in Molecular Biophysics and Biochemistry. He then got his medical degree at the UCLA School of Medicine. He completed his internship in internal medicine at USC’s Huntington Memorial Hospital in Pasadena, and his ophthalmology residency at the UCLA’s Jules Stein Eye Institute. For over 18 years, Dr. Kawesch was one of the foremost ophthalmic surgeons in the US and has consulted with and was a team doctor for seven professional sports teams in California. He continues to work with the Oakland Raiders. He trained with the American Academy of Anti-Aging Medicine and helps men increase their vitality, lifespan and overall healthspan.
