Dosage strengths of Testosterone Cypionate/Propionate Injection available:
160/40 mg/mL 5 mL vial
160/40 mg/mL 5 mL vial
General Information: Testosterone was the first ever synthesized anabolic steroid, and testosterone cypionate is a slow-acting, long-ester, oil-based injectable testosterone compound that is commonly prescribed for the treatment of hypogonadism – low testosterone levels and various related symptoms in males.
Testosterone cypionate first appeared on the U.S. prescription drug market during the early 1950’s, as Depo-Testosterone by Upjohn, now Pharmacia & Upjohn. Due to testosterone cypionate’s vast similarity to the earlier released and slightly longer testosterone enanthate, it has received only limited global availability and is often identified as an American medication.
Testosterone propionate was first described in 1935 to increase synthetic testosterone’s therapeutic usefulness by slowing its release into the bloodstream. It was released for clinical use two years later by Schering AG in Germany, featured in a hybrid blend with testosterone enanthate under the brand name Testoviron. This was also the first commercially available version on the U.S. prescription drug market and remained the dominant form of testosterone globally prior to 1960.
Testosterone is the primary androgen found in the body. Endogenous testosterone is synthesized by cells in the testis, ovary, and adrenal cortex. Therapeutically, testosterone is used in the management of hypogonadism, either congenital or acquired. Testosterone is also the most effective exogenous androgen for the palliative treatment of carcinoma of the breast in postmenopausal women. Testosterone was in use in 1938 and approved by the FDA in 1939. Anabolic steroids, derivatives of testosterone, have been used illicitly and are now controlled substances. Testosterone, like many anabolic steroids, was classified as a controlled substance in 1991. Testosterone is administered parenterally in regular and delayed-release (depot) dosage forms. In September 1995, the FDA initially approved testosterone transdermal patches (Androderm); many transdermal forms and brands are now available including implants, gels, and topical solutions. A testosterone buccal system, Striant, was FDA approved in July 2003; the system is a mucoadhesive product that adheres to the buccal mucosa and provides a controlled and sustained release of testosterone. In May 2014, the FDA approved an intranasal gel formulation (Natesto). A transdermal patch (Intrinsa) for hormone replacement in women is under investigation; the daily dosages used in women are much lower than for products used in males.
The FDA ruled in late 2004 that it would delay the approval of Intrinsa women's testosterone patch and has required more data regarding safety, especially in relation to cardiovascular and breast health.
The Cypionate Ester: An ester is any of a class of organic compounds that react with water to produce alcohols and organic or inorganic acids. Most esters are derived from carboxylic acids, and injectable testosterone is typically administered along with one or multiple esters. The addition of a carbon chain (ester) attached to the testosterone molecule controls how soluble it will be once inside the bloodstream. The smaller the carbon chain, the shorter the ester, and the more soluble the medication. A small/short will have a shorter half life – a repeating cycle of a medication’s time within the body. The inverse is true of long carbon chains, like cypionate, which both act slowly upon the body and evacuates the body at a similar rate.
The Propionate Ester: An ester is any of a class of organic compounds that react with water to produce alcohols and organic or inorganic acids. Most esters are derived from carboxylic acids, and injectable testosterone is typically administered along with one or multiple esters. The addition of a carbon chain (ester) attached to the testosterone molecule controls how soluble it will be once it’s inside the bloodstream. The larger the carbon chain, the longer the ester, and the less soluble the medication; a large/long ester will have a longer half-life. The inverse is true of short carbon chains, like the propionate ester, which acts rapidly upon the body and evacuates the body at a similar rate. With a three-carbon chain, the testosterone ester possesses the shortest half life of all testosterone esters at 4 days.
Mechanism of Action: Endogenous testosterone is responsible for sexual maturation at all stages of development throughout life. Synthetically, it is prepared from cholesterol. The function of androgens in male development begins in the fetus, is crucial during puberty, and continues to play an important role in the adult male. Women also secrete small amounts of testosterone from the ovaries. The secretion of androgens from the adrenal cortex is insufficient to maintain male sexuality.
Increased androgen plasma concentrations suppress gonadotropin-releasing hormone (reducing endogenous testosterone), luteinizing hormone, and follicle-stimulating hormone by a negative-feedback mechanism. Testosterone also affects the formation of erythropoietin, the balance of calcium, and blood glucose. Androgens have a high lipid solubility, enabling them to rapidly enter cells of target tissues. Within the cells, testosterone undergoes enzymatic conversion to 5-alpha-dihydrotestosterone and forms a loosely bound complex with cystolic receptors. Androgen action arises from the initiation of transcription and cellular changes in the nucleus brought about by this steroid-receptor complex.
Normally, endogenous androgens stimulate RNA polymerase, resulting in an increased protein production.These proteins are responsible for normal male sexual development, including the growth and maturation of the prostate, seminal vesicle, penis, and scrotum. During puberty, androgens cause a sudden increase in growth and development of muscle, with redistribution of body fat. Changes also take place in the larynx and vocal cords, deepening the voice. Puberty is completed with beard development and growth of body hair. Fusion of the epiphyses and termination of growth is also governed by the androgens, as is the maintenance of spermatogenesis. When endogenous androgens are unavailable, use of exogenous androgens are necessary for normal male growth and development.
Pharmacokinetics: Testosterone is administered intramuscularly (IM), to the skin as a topical gel, solution, ointment or transdermal systems for transdermal absorption, by implantation of long-acting pellets, or via buccal systems.
Testosterone is administered intramuscularly (IM); via subcutaneous injection; to the skin as a topical gel, solution, ointment or transdermal systems for transdermal absorption; by implantation of long-acting pellets, or; via buccal systems.
In serum, testosterone is bound to protein. It has a high affinity for sex hormone binding globulin (SHBG) and a low affinity for albumin. The albumin-bound portion freely dissociates. The affinity for SHBG changes throughout life. It is high during prepuberty, declines during adolescence and adult life, then rises again in old age. The active metabolite DHT has a greater affinity for SHBG than testosterone. Elimination half-life is 10—100 minutes and is dependent on the amount of free testosterone in the plasma.
Testosterone is metabolized primarily in the liver to various 17-keto steroids. It is a substrate for hepatic cytochrome P450 (CYP) 3A4 isoenzyme.1 Estradiol and dihydrotestosterone (DHT) are the major active metabolites, and DHT undergoes further metabolism. Testosterone activity appears to depend on formation of DHT, which binds to cytosol receptor proteins.
Further metabolism of DHT takes place in reproductive tissues. About 90% of an intramuscular testosterone dose is excreted in the urine as conjugates of glucuronic and sulfuric acids. About 6% is excreted in the feces, largely unconjugated. There is considerable variation in the half-life of testosterone as reported in the literature, ranging from 10 to 100 minutes.2
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp
Testosterone is a substrate for CYP3A4 and is also both transported by and an inhibitor of P-glycoprotein (P-gp) transport.13
Intramuscular Route: Parenteral testosterone formulations have been developed that reduce the rate of testosterone secretion, with esters being less polar and slowly absorbed from intramuscular sites. Esters have a duration of action of 2—4 weeks following IM administration. The esters are hydrolyzed to free testosterone, which is inactivated in the liver.
Subcutaneous Route: The duration of action of testosterone subcutaneous implantable pellets (Testopel) is usually 3—4 months, but may last as long as 6 months.
Indications: Testosterone Cypionate injections are primarily used I men who do not make enough testosterone naturally (hypogonadism), as well as in specific adolescent cases to induce puberty in those with delayed puberty.
Contraindications/Precautions: Who should not take this medication? Children should not use testosterone unless directed otherwise by a physician. Your health care provider needs to know if you have any of these conditions: breast cancer; breathing problems while sleeping; diabetes; heart disease; if a female partner is pregnant or trying to get pregnant; kidney disease; liver disease; lung disease; prostate cancer, enlargement; any unusual or allergic reactions to testosterone or other products; pregnant or trying to get pregnant; breast-feeding. Your healthcare provider will need to have regular bloodwork drawn while on testosterone. This medication is banned from use in athltes by most athletic organizations..
Who should not take this medication? Children should not use testosterone unless directed otherwise by a physician. Your health care provider needs to know if you have any of these conditions: breast cancer; breathing problems while sleeping; diabetes; heart disease; if a female partner is pregnant or trying to get pregnant; kidney disease; liver disease; lung disease; prostate cancer, enlargement; any unusual or allergic reactions to testosterone or other products; pregnant or trying to get pregnant; breast-feeding. Your healthcare provider will need to have regular bloodwork drawn while on testosterone. This medication is banned from use in athletes by most athletic organizations.
The manufacturers of AndroGel and Striant state that their products are contraindicated in patients with soybean, soy, or soya lecithin hypersensitivity because they are derived partially from soy plants. Topical gels and solutions are typically flammable, therefore exposure to fire, flame, and tobacco smoking should be avoided while using any topical gel or solution formulation of testosterone. Testosterone undecanoate (Aveed) oil for injection contains benzyl benzoate, the ester of benzyl alcohol and benzoic acid, and refined castor oil. Therefore, testosterone undecanoate use is contraindicated in patients with polyoxyethylated castor oil hypersensitivity, benzoic acid hypersensitivity, or benzyl alcohol hypersensitivity.4
Because some testosterone transdermal systems (e.g., Androderm) contain aluminum or other metal components, patients should be instructed to remove the patch before undergoing magnetic resonance imaging (MRI). Metal components contained in the backing of some transdermal systems can overheat during an MRI scan and cause skin burns in the area where the patch is adhered.
Testosterone injections are administered intramuscularly. Do not inject via intravenous administration. Respiratory adverse events have been reported immediately after intramuscular administration of testosterone enanthate and testosterone undecanoate. Care should be taken to ensure slow and deep gluteal muscle injection of testosterone.4
Testosterone can stimulate the growth of cancerous tissue and is contraindicated in male patients with prostate cancer or breast cancer. Patients with prostatic hypertrophy should be treated with caution because androgen therapy may cause a worsening of the signs and symptoms of benign prostatic hypertrophy and may increase the risk for development of malignancy. Elderly patients and other patients with clinical or demographic characteristics that are recognized to be associated with an increased risk of prostate cancer should be evaluated for the presence of prostate cancer prior to initiation of testosterone replacement therapy. In patients receiving testosterone therapy, surveillance for prostate cancer should be consistent with current practices for eugonadal men. Testosterone replacement is not indicated in geriatric patients who have age-related hypogonadism only or andropause because there is insufficient safety and efficacy information to support such use.5 Additionally, the efficacy and long-term safety of testosterone topical solution in patients over 65 years of age has not been determined due to an insufficient number of geriatric patients involved in controlled trials.6 According to the Beers Criteria, testosterone is considered a potentially inappropriate medication (PIM) for use in geriatric patients and should be avoided due to the potential for cardiac problems and its contraindication in prostate cancer. The Beers expert panel considers use for moderate to severe hypogonadism to be acceptable.7
Because of reduced drug clearance and an increased risk of drug accumulation, patients with hepatic disease or hepatic dysfunction should be prescribed testosterone with caution. In addition, edema secondary to water and sodium retention may occur during treatment with androgens. Use testosterone with caution in patients with hepatic disease; renal disease, including nephritis and nephrosis; preexisting edema; or cardiac disease, including heart failure, coronary artery disease, and myocardial infarction (MI), as fluid retention may aggravate these conditions. Further, the possible association between testosterone use and the increased risk of severe cardiovascular events, irrespective of pre-existing cardiac disease, is currently under investigation. An observational study in the U.S. Veteran Affairs health system included adult male patients of an average age of 60 years. Patients (n = 8709) undergoing coronary angiography with a recorded low serum testosterone concentration of < 300 ng/dl were included in the retrospective analysis. Within the larger cohort, testosterone therapy was initiated in 1223 males after a median of 531 days following coronary angiography; 7486 males did not receive testosterone therapy. Three years after coronary angiography, 25.7% of patients receiving testosterone therapy compared to 19.9% of patients not receiving therapy suffered a severe and/or fatal cardiovascular event (MI, stroke, death).8 A second observational study, investigated the incidence of acute non-fatal MI following an initial testosterone prescription in both younger (<= 55 years) and older (>= 65 years) adult males (n = 55,593). The incidence rate of MI occurring within 90 days following the initial testosterone prescription was compared to the incidence rate of MI occurring in the one year leading-up to the first prescription. Among older males, a 2-fold increase in the risk of MI was observed within the 90 day window; among younger males with a pre-existing history of cardiac disease, a 2- to 3-fold increased risk of MI was observed. In contrast, no increased risk was observed in younger males without a history of cardiac disease.9 In light of these findings, the FDA announced in early 2014 an examination into the possible link between testosterone therapy and severe cardiovascular events. The FDA has NOT concluded that FDA-approved testosterone treatment increases the risk of stroke, MI, or death. However, health care professionals are urged to carefully consider whether the benefits of treatment are likely to exceed the potential risks. The FDA will communicate their final conclusions and recommendations when the evaluation is complete.
The treatment of hypogonadal men with testosterone esters may potentiate sleep apnea, especially in patients that have risk factors for apnea such as obesity or chronic pulmonary disease. In addition, the safety and efficacy of testosterone topical solution and intranasal gel in obese males with BMI > 35 kg/m2 has not been established.
Patients receiving high doses of testosterone are at risk for polycythemia. Periodically, patients receiving testosterone should have their hemoglobin and hematocrit concentrations measured to detect polycythemia.
Testosterone is contraindicated during pregnancy because of probable adverse effects on the fetus (FDA pregnancy risk category X). Women of childbearing potential who are receiving testosterone treatments should utilize adequate contraception. Because testosterone is not used during pregnancy, there should be no particular reason to administer the products to women during labor or obstetric delivery; safety and efficacy in these settings have not been established.
Testim testosterone gel is specifically contraindicated in females; the drug is for males only; the dosage form supplies testosterone in excess of what should be prescribed to females under certain endocrine situations. In addition, Androgel, Androderm, Aveed, Fortesta, and Striant brand products are not indicated for use in females due to lack of controlled evaluations and/or the potential for virilizing effects.Female patients receiving other forms of testosterone therapy should be closely monitored for signs of virilization (deepening of the voice, hirsutism, acne, clitoromegaly, and menstrual irregularities). At high doses, virilization is common and is not prevented by concomitant use of estrogens. Some virilization may be judged to be acceptable during treatment for breast carcinoma; however, if mild virilism is evident, discontinuation of drug therapy is necessary to prevent long term virilization. Females should be aware that accidental exposure to some testosterone dosage forms (i.e., ointments, solutions, and gels) may occur if they come into direct contact with a treated patient. In clinical studies, within 2—12 hours of gel application by male subjects, 15-minute sessions of vigorous skin-to-skin contact with a female partner resulted in serum female testosterone levels > 2 times the female baseline values. When clothing covered the treated site on the male, the transfer of testosterone to the female was avoided. Accidental exposure to topical testosterone gel has also occurred in pediatric patients after contact between the child and the application site in treated individuals. The adverse events reported include genitalia enlargement, development of pubic hair, advanced bone age, increased libido, and aggressive behavior. Symptoms resolved in most patients when exposure to the product stopped. However, in a few patients, the genitalia enlargement and advanced bone age did not fully return to expected measurements. The FDA recommends taking precautions to minimize the potential for accidental exposure of topical testosterone products by washing hands with soap and warm water after each application, covering application site with clothing, and removing medication with soap and water when contact with another person is anticipated. In the case of direct skin-to-skin contact with the site of testosterone application, the non-treated person should wash the area with soap and water as soon as possible.
Testosterone topical solution, transdermal patches, and gels are contraindicated in lactating women who are breast-feeding. It is recommended that other testosterone formulations be avoided during breast-feeding as well. Testosterone distribution into breast milk has not been determined; it is unclear if exposure would increase above levels normally found in human milk. Significant exposure to this androgen via breast-feeding may have adverse androgenic effects on the infant and the drug may also interfere with proper establishment of lactation in the mother.
Historically, testosterone/androgens have been used adjunctively for lactation suppression.17 Alternative methods to breast-feeding are recommended in lactating women receiving testosterone therapy.
Androgen therapy, such as testosterone, can result in loss of diabetic control and should be used with caution in patients with diabetes mellitus. Close monitoring of blood glucose is recommended.
Testosterone has induced osteolysis and should be used with caution in patients with hypercalcemia, which can be exacerbated in patients with metastatic breast cancer.
Administration of testosterone undecanoate has been associated with cases of serious pulmonary oil microembolism (POME) reactions as well anaphylactoid reactions. Reported cases of POME reactions occurred during or immediately after a 1000 mg intramuscular injection of testosterone undecanoate.
Symptoms included: cough, urge to cough, dyspnea, hyperhidrosis, throat tightening, chest pain, dizziness, and syncope. Most cases lasted a few minutes and resolved with supportive measures; however, some lasted up to several hours, and some required emergency care and/or hospitalization. When administering testosterone undecanoate, clinicians should take care to inject deeply into the gluteal muscle, avoiding intravascular injection. In addition to POME reactions, episodes of anaphylaxis, including life-threatening reactions, have also been reported following the intramuscular injection of testosterone undecanoate. Patients with suspected hypersensitivity reactions should not be retreated with testosterone undecanoate.
After every administration, monitor patient for 30 minutes and provide appropriate medical treatment in the event of serious POME or anaphylactoid reactions. Due to the risk of serious POME and anaphylaxis reactions, testosterone undecanoate (Aveed) is only available through a restricted program called the Aveed REMS Program. Clinicians wanting to prescribe Aveed, must be certified with the REMS Program for purposes of ordering or dispensing the product. Healthcare settings must also be certified with the REMS Program and must have the resources to provide emergency medical treatment in cases of serious POME and anaphylaxis.
Further information is available at www.AveedREMS.com or call 1—855—755—0494.
Intranasal formulations of testosterone (e.g., Natesto) are not recommended for individuals with a history of nasal disorders such as nasal polyps; nasal septal perforation; nasal surgery; nasal trauma resulting in nasal fracture within the previous 6 months or nasal fracture that caused a deviated anterior nasal septum; sinus surgery or sinus disease. In addition, the safety and efficacy of intranasal testosterone has not been evaluated in individuals with mucosal inflammatory disorders such as Sjogren's syndrome. Patients with rhinorrhea (rhinitis) who are receiving intranasal formulations of testosterone may experience decreased medication absorption secondary to nasal discharge. These patients may experience a blunted or impeded response to the intranasal medication. In clinical evaluation, serum total testosterone concentrations were decreased by 21—24% in males with symptomatic allergic rhinitis, whether treated with nasal decongestants or left untreated. Treatment with intranasal testosterone should be delayed until symptoms resolve in patients with nasal congestion, allergic rhinitis, or upper respiratory infection. If severe rhinitis symptoms persist, an alternative testosterone replacement therapy is advised.
The safety and efficacy of testosterone topical products Androgel, Axiron, Fortesta, and Testim as well as Striant buccal tablets, Natesto intranasal gel, and Aveed injectable testosterone undecenoate have not been established in neonates, infants, children, and adolescents < 18 years old. In addition, the safety and efficacy Depo-Testosterone injection has not be established in children < 12 years,16 and Androdem patches have not been evaluated in pediatric patients < 15 years.
Generally, the use of testosterone in children should be undertaken only with extreme caution. Testosterone may accelerate bone maturation without stimulating compensatory linear growth, sometimes resulting in compromised adult stature. If testosterone is administered to prepubertal males, radiographic examinations of the hand and wrist should be performed every 6 months to assess the rate of bone maturation and the effect of the drug on epiphyseal centers. Once the epiphyses have closed, growth is terminated. Even after discontinuation of treatment, epiphyseal closure can be enhanced for several months. Accidental exposure to topical testosterone gel has also occurred in pediatric patients after skin to skin contact between the child and the application site in treated individuals. The adverse events reported include genitalia enlargement, development of pubic hair, advanced bone age, increased libido, and aggressive behavior. Symptoms resolved in most patients when exposure to the product stopped. However, in a few patients, the genitalia enlargement and advanced bone age did not fully return to expected measurements. The FDA recommends taking precautions to minimize the potential for accidental exposure by washing hands with soap and warm water after each application, covering application site with clothing, and removing medication with soap and water when contact with another person is anticipated. In the case of direct skin-to-skin contact with the site of testosterone application, the non-treated person should wash the area with soap and water as soon as possible.
Pregnancy: Testosterone is contraindicated during pregnancy because of probable adverse effects on the fetus (FDA pregnancy risk category X). Women of childbearing potential who are receiving testosterone treatments should utilize adequate contraception. Because testosterone is not used during pregnancy, there should be no particular reason to administer the products to women during labor or obstetric delivery; safety and efficacy in these settings have not been established.
Breast-feeding: Testosterone topical solution, transdermal patches, and gels are contraindicated in lactating women who are breast-feeding. It is recommended that other testosterone formulations be avoided during breast-feeding as well.
Testosterone distribution into breast milk has not been determined; it is unclear if exposure would increase above levels normally found in human milk. Significant exposure to this androgen via breast-feeding may have adverse androgenic effects on the infant and the drug may also interfere with proper establishment of lactation in the mother.17 Historically, testosterone/androgens have been used adjunctively for lactation suppression.17 Alternative methods to breast-feeding are recommended in lactating women receiving testosterone therapy.
Interactions: Possible interactions include: certain medicines for diabetes; certain medicines that treat or prevent blood clots like warfarin; oxyphenbutazone; propranolol; steroid medicines like prednisone or cortisone. This list may not describe all possible interactions.
NOTE: Testosterone is a substrate for hepatic cytochrome P450 (CYP) 3A4 isoenzyme.
Testosterone is also both transported by and an inhibitor of P-glycoprotein transport.
Testosterone can increase the anticoagulant action of warfarin. Serious bleeding has been reported in some patients with this drug-drug interaction. Although the mechanism is unclear, testosterone may reduce procoagulant factors. Reduction of warfarin dosage may be necessary if testosterone therapy is coadministered. More frequent monitoring of INR and prothrombin time in patients taking such oral anticoagulants is recommneded, especially at the initiation and termination of androgen therapy.2 It is unclear if testosterone can augment the anticoagulant response to heparin therapy or if testosterone alters the effect of other non-coumarin oral anticoagulants in a similar manner.
Based on case reports with methyltestosterone and danazol, androgens may increase plasma concentrations of cyclosporine, leading to a greater risk of nephrotoxicity.
Coadministration of corticosteroids and testoterone may increase the risk of edema, especially in patients with underlying cardiac or hepatic disease. Corticosteroids with greater mineralocorticoid activity, such as fludrocortisone, may be more likely to cause edema. Administer these drugs in combination with caution.
Goserelin and leuprolide inhibit steroidogenesis. Concomitant use of androgens with goserelin or leuprolide is relatively contraindicated and would defeat the purpose of goserelin or leuprolide therapy.
Androgens can increase the risk of hepatotoxicity and therefore should be used with caution when administered concomitantly with other hepatotoxic medications. Patients should be monitored closely for signs of liver damage, especially those with a history of liver disease.
Androgens may be necessary to assist in the growth response to human growth hormone, but excessive doses of androgens in prepubescent males can accelerate epiphyseal maturation.
Androgens are known to stimulate erythropoiesis.
Despite the fact that endogenous generation of erythropoietin is depressed in patients with chronic renal failure, other tissues besides the kidney can synthesize erythropoietin, albeit in small amounts. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
The antiandrogenic effects of the 5-alpha reductase inhibitors (i.e., dutasteride, finasteride) are antagonistic to the actions of androgens; it would be illogical for patients taking androgens to use these antiandrogenic drugs.
Drug interactions with Saw palmetto, Serenoa repens have not been specifically studied or reported. Saw palmetto extracts appear to have antiandrogenic effects. The antiandrogenic effects of Saw palmetto, Serenoa repens would be expected to antagonize the actions of androgens; it would seem illogical for patients taking androgens to use this herbal supplement.
Limited data suggest that testosterone concentrations increase during fluconazole administration. It appears that fluconazole doses of 200 mg/day or greater are more likely to produce this effect than doses of 25—50 mg/day. The clinical significance of this interaction is unclear at this time. Although data are not available, a similar reaction may occur with voriconazole. Both fluconazole and voriconazole are inhibitors of CYP3A4, the hepatic microsomal isoenzyme responsible for metabolism of testosterone.
Exogenously administered androgens (testosterone derivatives or anabolic steroids) have variable effects on blood glucose control in patients with diabetes mellitus. In general, low testosterone concentrations are associated with insulin resistance. Further, when hypogonadal men (with or without diabetes) are administered exogenous androgens, glycemic control typically improves as indicated by significant reductions in fasting plasma glucose concentrations and HbA1c. In one study in men with diabetes, testosterone undecenoate 120 mg PO/day for 3 months decreased HbA1c concentrations from a baseline of 10.4% to 8.6% (p < 0.05); fasting plasma glucose concentrations decreased from 8 mmol/l at baseline to 6 mmol/l (p < 0.05). Significant reductions in HbA1c and fasting plasma glucose concentrations did not occur in patients taking placebo.36 Similar results have been demonstrated with intramuscular testosterone 200 mg administered every 2 weeks for 3 months in hypogonadal men with diabetes.37 In healthy men, testosterone enanthate 300 mg IM/week for 6 weeks or nandrolone 300 mg/week IM for 6 weeks did not adversely affect glycemic control; however, nandrolone improved non-insulin mediated glucose disposal.
It should be noted that some studies have shown that testosterone supplementation in hypogonadal men has no effect on glycemic control.Conversely, the administration of large doses of anabolic steroids in power lifters decreased glucose tolerance, possibly through inducing insulin resistance.41 While data are conflicting, it would be prudent to monitor all patients with type 2 diabetes on antidiabetic agents receiving androgens for changes in glycemic control, regardless of endogenous testosterone concentrations. Hypoglycemia or hyperglycemia can occur; dosage adjustments of the antidiabetic agent may be necessary.
In vitro, both genistein and daidzein inhibit 5 alpha-reductase isoenzyme II, resulting in decreased conversion of testosterone to the potent androgen 5-alpha-dihydrotestosterone (DHT) and a subsequent reduction in testosterone-dependent tissue proliferation.42 The action is similar to that of finasteride, but is thought to be less potent. Theoretically, because the soy isoflavones appear to inhibit type II 5-alpha-reductase, the soy isoflavones may counteract the activity of the androgens.
Conivaptan is a potent inhibitor of CYP3A4 and may increase plasma concentrations of drugs that are primarily metabolized by CYP3A4. Testosterone is a substrate for CYP3A4 isoenzymes. The clinical significance of this theoretical interaction is not known.
Testosterone is an inhibitor of P-glycoprotein transport.35 Ranolazine is a substrate of P-glycoprotein, and inhibitors of P-glycoprotein may increase the absorption of ranolazine. In addition, ranolazine inhibits CYP3A and may increase plasma concentrations of drugs that are primarily metabolized by CYP3A4 such as testosterone.
Ambrisentan is a substrate for P-glycoprotein transport, an energy-dependent drug efflux pump. The inhibition of P-glycoprotein, by drugs such as testosterone, may lead to a decrease in the intestinal metabolism and an increase in the oral absorption of ambrisentan. If ambrisentan is coadministered with a P-glycoprotein inhibitor, patients should be monitored closely for adverse effects.
Coadministration of oxyphenbutazone and testosterone may lead to elevated concentrations of oxyphenbutazone. Monitor patients for adverse effects when coadministering these drugs together.