Testosterone levels do a variety of tasks in the body other than regulating libido, and it’s well known that men need adequate levels for healthy sexual function, but did you know even women need enough testosterone to function normally? For cellular development, immunity, and a healthy nervous system, testosterone is essential.
Worldwide, numerous academics and medical professionals are becoming aware of the lack of testosterone in people with chronic pain. The use of testosterone therapy in the treatment of chronic pain is quickly becoming a requirement due to its crucial role in pain control and management. Let’s examine the connection between low testosterone and chronic pain and look at the many advantages of low-T therapy.
Why the Necessity of Testosterone?
Unfortunately, the misconception that testosterone is just the hormone required for male libido and erectile function arises when the word “testosterone” is mentioned. One of many essential biological functions of testosterone (see Table 1) is this one. Furthermore, both male and female chronic pain patients require adequate levels of biologic testosterone. First, since testosterone is intricately linked to endogenous opioid activity, adequate testosterone levels are required for effective pain management. Additionally, testosterone is required for the activation of dopamine and norepinephrine activity, maintenance of blood-brain barrier transport, and binding to opioid receptors. Therefore, a lack of testosterone activity in the CNS could cause poor pain management, depression, sleep issues, and a lack of vigor and drive. Testosterone serves as the main androgenic substance for tissue repair in the periphery. 7 It has long been understood that adequate testosterone levels are essential for bone health, exercise tolerance, and muscle maintenance. It is known that both men and women with low testosterone can develop compression fractures. Therefore, a lack of testosterone affects the ability to heal wounds and control inflammation at pain sites.
| Opioid receptor binding Dopamine-norepinephrine activity Maintenance of blood-brain barrier Androgenic-healing/tissue growth Libido Erectile activity (males) Maintenance of muscle and bone mass Exercise tolerance |
Another common misunderstanding is that testosterone is only a hormone that affects men. Even in females, libido requires a sufficient level of testosterone in the blood. Furthermore, testosterone’s entire range of CNS and androgenic-immunologic effects are also applicable to women. The only distinction and factor with regard to TR in females is that they typically require a lower dosage for replacement due to their lower serum concentration.
Gonadotropin-releasing hormone (GnRH), which is produced by the hypothalamus, stimulates the pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The production of testosterone by the adrenal and gonads is aided by FSH and LH. Although it was previously believed that testosterone could only be produced in the testicles, it is now known that it can also be produced in the ovary and adrenal gland (see Figure 1). The fact that testosterone changes into estradiol and dihydrotestosterone in peripheral tissue is extremely significant. Due to their effects on the CNS and bone formation, estrogens are known to have a strong impact on depression. Although our knowledge is limited, it seems certain that the CNS undergoes anatomical changes as a result of severe, uncontrolled pain due to neuroplasticity. In order to effectively treat a CNS that has been altered as a result of severe chronic pain, hormone therapy is becoming increasingly important.
Mechanism of Testosterone Depletion
A patient with chronic pain may experience testosterone depletion for one of two reasons (see Table 2). One is pituitary insufficiency caused by severe pain, per se. Over time, constant, persistent, unrelieved pain will put enough stress on the hypothalamus and pituitary (GnRH, LH, and FSH) to result in insufficient testosterone secretion from the adrenal and gonads. When hypothalamic-pituitary insufficiency is the cause of hypotestosteronemia, other hormones like cortisol, pregnenolone, or thyroid may likely display serum deficiencies. Opioid administration is the second-most prevalent cause of low testosterone. Almost all oral and intrathecal opioids have been associated with low testosterone levels. 2–5 Opioid suppression of GnRH in the hypothalamus is the main cause of low testosterone serum levels. Additionally, testosterone production in the gonads or adrenal can be negatively impacted by opioids. Both causes of hypotestosteronemia may simultaneously exist. Also, both cases require testosterone replacement. If opioid-specific, dose-related, or connected to opioid serum levels, testosterone suppression by opioids is unknown.
| Pituitary deficiency caused by over- stress of uncontrolled chronic pain Opioid administration |
Testing For Testosterone Deficiency
Simply order a morning serum testosterone level. The serum concentration of a patient is now reported by laboratories, along with average values for men and women. Units of measure may vary between laboratories. The total serum testosterone concentration has protein-bound and unbound components. The portion most thought to be involved with libido and sexual function is generally thought to be the free, bioavailable, or unbound component. Although protein-bound testosterone may be required to either enter certain body compartments, such as the CNS, spinal cord, or pain site, in order to perform its essential functions, we think that the total serum testosterone levels may be a more important evaluation for pain management purposes. As a result, pain specialists should take into account that low levels of either total serum testosterone or free unbound testosterone can signify a deficiency that needs to be corrected.
Who Should Be Tested
All patients with chronic pain who need opioid administration, including those who are already taking opioids, should be screened if there are financial resources available. Serum testing is clearly indicated for patients who are receiving opioid therapy and who report fatigue, poor pain management, depression, weakness, and low libido (see Tables 3 and 4).
| Lack of energy Loss of libido Depression Poor healing Diminished opioid affects Loss of motivation Apathy Weakness |
| Single, morning serum test for total and free testosterone. Start patients on a commercial testosterone preparation. Assess treatment response 2 to 4 weeks after starting therapy: assess for energy, endurance, libido, motivation, pain relief, and sleep pattern. |
You can pick from a variety of commercial testosterone products (see Table 5) Each has pros and cons and all are relatively expensive. The highly variable nature of third-party payments may influence your decision. Patients without insurance will typically be forced to use injectable testosterone due to cost considerations. The price of some compounding pharmacies’ topical testosterone creams or gels is now comparable to the price of injectable testosterone. %20If%20you%20use%20a%20compounding%20pharmacy,%20we%20recommend%20you%20order%20a%20testosterone%20concentration%20similar%20to%20that%20found%20in%20the%20commercial%20gels%20which%20is%20a%201%%20testosterone%20concentration For example, 50mg in 5gms (Testim®, Androgel®).
| Trade Name | Dosage |
|---|---|
| Andro-Gel® | 1% gel in pump bottle |
| Testim® | 1% gel in a 5gm tube |
| Androderm® | 2.5 and 5.0mg patches |
| Generic Injectable | 100 or 200mg per ml in oil/depot base |
| Note: Starting female dosage is 25% that of male dosage. | |
Every commercial product is designed and labeled for use by men. %20We%20recommend%20a%20starting%20female%20dosage%20that%20is%20about%2025%%20that%20of%20the%20male%20dosage Since testosterone use in females is currently “off-label,” doctors may want to use an off-label consent form or make a note in the patient’s chart stating that they are aware of the off-label use. 10 As with all therapeutic drug classes, there are differences between the readily available commercial products. These variations include the timing of the onset of action, the serum concentration, the duration of the action, and the route of administration. Patients may, in fact, ask for a different testosterone preparation based on any commercial product variations. Consequently, no commercial preference is recommended at this time.
Patients frequently report improvement in symptoms like libido, energy, opioid effectiveness, depression, and weakness if the testosterone dosage is appropriate. To demonstrate efficacy and support the cost of the treatment, the patient’s record should reflect any improvement in symptoms.
It is advised to check your serum concentration again every three to six months and then once a year. The ideal testosterone dosage is one that raises serum concentration into the normal range. There is no upper limit on testosterone dosage. Reduced pain and the signs of low testosterone are the main treatment objectives (see Tables 1 and 3).
Unfortunately, the highly-publicized androgenic side-effects of anabolic steroids observed in some athletes have led some people to believe incorrectly that testosterone replacement in both men and women is associated with the same risks. Testosterone is a Schedule III drug under the U. S. Controlled Substance Act and is classified as an “anabolic steroid. Its anabolic (tissue-building) effects are indeed desired for pain relief. The dosages of testosterone and synthetic anabolic steroids used by athletes for competitive advantage far exceed those used to replace testosterone in pain patients. The dosages suggested here and by commercial manufacturers have not yet resulted in any adrogenic side effects in either males or females. Erectile dysfunction, testicular or liver cancer, hypertension, liver deterioration, and cardiomyopathy are a few of the side effects that have been associated with athletes who use supraphysiologic dosages. Before these severe side effects, testosterone replacement therapy typically results in acne or, in females, beard growth, enabling the doctor to quickly determine that the dosage is excessive. It would be natural to need to reduce or stop the testosterone dosage if acne, hair growth, or voice changes were seen.
Alternative-Human Chorionic Gonadotropin (HCG)
HCG is available as a nasal spray or as an injectable medication with 1,000 units per milliliter. It increases serum levels of testosterone and can be used alone or in conjunction with a commercial testosterone preparation. HCG may cost a little less than some commercial testosterone supplements.
Many pain patients report that precursor therapy with testosterone replacement is a helpful adjunct. Dehydro-epiandrosterone (DHEA), pregnenolone, progesterone, and androstenedione are the four testosterone precursors that can be tested therapeutically (see Figure 1 and Table 6).
| Precursor | Daily Dosage |
|---|---|
| Dehydroepiandrosterone (DHEA) | 50 to 100mg |
| Pregnenolone | 50 to 100mg |
| Androstenedione | 50 to 100mg |
| Medroxyprogesterone | 10 to 20mg |
| Note: Intermittent, rather than daily, administration is recommended. | |
The beneficial theory for precursors as adjuncts is twofold:
- Natural testosterone production is enhanced,
- The biologic pathway of testosterone production may not be suppressed by precursors, preventing any negative feedback (see Figure 1).
DHEA and androstenedione have been shown to have a favorable impact on corticosteroid or testosterone production despite the paucity of studies on precursor therapy. 20–22 Precursors are very safe and don’t seem to have many side effects. We advise using them occasionally rather than daily out of caution rather than daily
Therapeutic Trial Without a Blood Test
Many people with pain are unable to afford getting their serum testosterone levels taken. Take a history of any symptoms of testosterone deficiency in these circumstances (see Tables 1 and 3). A therapeutic trial without a blood test is necessary if the patient is taking opioids and reports a lot of these symptoms. Simply give 1. 0ml (200mg) of testosterone for injection or a one-week supply of a brand-name testosterone supplement The patient will report a significant improvement in symptoms within a week if testosterone deficiency is the underlying cause of their symptoms. An ongoing treatment strategy for testing, treatment, and evaluation based on financial resources can be created once a connection between low testosterone and symptoms is established.
Concomitant Use of Erectile Dysfunction Drugs
Although testosterone is essential for erectile function, erectile dysfunction can also be brought on by vascular and neurological processes. Patients with chronic pain are more likely to experience neuropathic injury to the abdominal, pelvic, or spinal nerves. Due to their high rates of corticoid dysfunction, hypercholesterolemia, and relative inactivity, people with pain also have a high prevalence of vascular disease. In the event that testosterone replacement therapy is unsuccessful in treating erectile dysfunction, sildenafil (Viagra®), tadafil (Cialis®), or vardenafil (Levitra®) may be used concurrently.
Consultation With Other Physicians
Testosterone testing and treatment is easily accomplished. Co-management and consultation with an endocrinologist are options to be taken into consideration if patients need multiple hormone replacements, which is common in hypothalamic-pituitary suppression.
Case 1: Simple Testosterone Replacement—Male. A 54-year-old man has right neck, shoulder, and arm neuropathies as a result of a cervical neck/shoulder injury, which has left him in excruciating pain. He needs multiple long- and short-acting opioids, as well as a sedative before bed, to manage his severe, ongoing pain. His serum testosterone level was 204ng/dl (normal range 241-227). He maintains on depotestosterone, 200mg every two weeks. He experiences depression, insomnia, pain flare-ups, lethargy, and loss of libido if he skips an injection.
Case 2: Testosterone Replacement With Adjunct Therapy—Male. Three lumbar herniated discs in a 44-year-old man required fusion and metal rod placement. After being started on several opioids, he underperformed and was referred for medical assessment and management. His serum testosterone was 154ng/dl (Normal 241-827ng/dl). His pain drastically decreased and his energy, drive, and libido rose within days of beginning a testosterone gel of 50 mg per day. His libido and physical prowess were greatly enhanced by the addition of oral medroxyprogesterone 10mg, twice daily. He has transitioned from a bed/housebound state to one where he is active every day and can work part-time thanks to testosterone and its precursor, progesterone.
Case 3: Simple Testosterone Replacement—Female. A 48-year-old woman was involved in a car crash at age 31. She experienced constant, debilitating pain in her face and neck as a result of facial and dental fractures. Fibromyalgia symptoms followed. She’s been receiving opioid treatment for around 17 years now. %20Serum%20testosterone%20con-centration%20was%206ng/dl%20(normal%20rage%20is%2012-90ng/dl)%20after%20which%20time%20she%20was%20started%20on%20topical%201%%20testosterone%20gel,%2025mg%20every%20other%20day She noticed an improvement in libido, pain management, stamina, and energy within two weeks.
Case 4: Testosterone Replacement With Adjunct Therapy—Female. A 53-year-old woman who gave birth to her fourth child via traumatic cesarean section. Internal bleeding required post-operative surgery. Six pelvic surgeries and one breast cancer procedure have already been performed on her. She subsequently developed chronic, excruciating pain that was unbearable and required multiple, high-dose opioid medications to manage. She experienced severe lumbar spine degeneration approximately 10 years after the onset of her pain, which prompted hormone testing. Her serum testosterone concentration was . 16ng/ml (normal range is 1. 75-7. 81ng/ml) indicating severe deficiency. She now uses 1,000 units of human chorionic gonadotropin every other day and 25 mg of testosterone topical gel every other day to maintain her condition. Her pain is well-controlled, and she has plenty of energy, libido, endurance, and sex. She works as a health professional, and thanks to her opioid and hormone regimen, she can only work about half the time. Her spine degeneration appears to have ceased.
The hypothalamic-pituitary-adrenal-gonadal axis’ overstimulation and hypofunction, as well as the long-term use of opioids, which may suppress the hypothalamus and pituitary, are all potential causes of testosterone deficiency in patients with severe, chronic pain. Both males and females need adequate testosterone serum levels for libido and sexual function in addition to other functions like cellular growth, healing, preservation of bone and muscle mass, and maintenance of opioid receptors, the blood-brain barrier, and dopamine-norepinephrine activity in the central nervous system. Poor pain management, weakness, lethargy, depression, sleep disturbances, and loss of libido are all symptoms of testosterone deficiency. Pain professionals should incorporate testosterone testing and replacement into their pain practice due to the crucial functions of testosterone in pain patients. Although it’s not entirely certain, testosterone replacement therapy may help some pain patients avoid neurologic and bone-related degeneration.
Resources
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FAQ
Can testosterone help with aches and pains?
Researchers have known for a long time that androgens reduce cartilage damage and inflammation. Importantly, evidence also suggests that men with low testosterone may benefit from testosterone replacement therapy to prevent joint pain and damage.
Does testosterone help with inflammation?
Systematic inflammation and an increase in metabolic risk are found to be related to low testosterone levels. Because it produces inflammatory cytokines, adipose tissue may help testosterone control inflammation.
Does testosterone help sciatica?
At four weeks, testosterone treatment (100 mg kg-1) significantly improved (p 05) Following sciatic nerve injury, testosterone reduces neuronal damage and slows the degeneration of motor neurons.
Does testosterone make you feel less pain?
Some guys who take narcotics with opioids for pain experience low testosterone levels. Low testosterone levels may increase a person’s sensitivity to pain, according to research.
Is testosterone a natural painkiller?
The researchers hypothesize that testosterone sets off a series of events that raises levels of enkephalins, a class of natural painkillers. This may occur in humans too.
What symptoms does testosterone help?
There’s no one-time fix for low testosterone. However, for many people assigned male at birth (AMAB) who experience low testosterone, regular hormone replacement therapy helps to increase energy levels, improve sex drive, and lessen the symptoms of depression. Treatment may also boost muscle mass and bone density.
Ask the Doc- Can growth hormones or testosterone help with flexer tendons, neck and foot pain?
Reference:
https://www.practicalpainmanagement.com/treatments/hormone-therapy/testosterone-replacement-chronic-pain-patients
https://www.practicalpainmanagement.com/treatments/hormone-therapy/testosterone-replacement-essential-pain-management