Topical Testosterone

1 - 200 mg/mL 30 mL Topi-Click Dispenser

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. Developed in the United States by Uniumed Pharmaceuticals as AndroGel, testosterone cream was FDA approved in 2000 for the treatment of testosterone deficiency, which often results in a variety of hypogonadic conditions from mood and energy to sexual dysfunctions, as well as a treatment for several injury-related conditions like those experienced by severe burn and accident victims. A very popular form of testosterone, AndroGel is sold around the world under a couple of less popular brand/trade names most notably Testogel (manufactured in the UK by Laboratoires Besins and distributed by Bayer), Testim (manufactured in the U.S. by Auxilium Pharmaceuticals, Inc.), and various generic versions often sold under the name testosterone cream or gel.The transdermal delivery system of testosterone cream targets the same, or at least very similar bodily regions as injections and other forms of testosterone. More specifically, maximum absorption of testosterone cream is achieved when (as with injectable testosterone) it's administered to densely muscled bodily regions. Since greater amounts of muscle at the point of application equates to a higher number of testosterone absorbing capillaries, testosterone can be more rapidly shuttled into the bloodstream.

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. Topical Route: Roughly 10% of an applied topical dosage of testosterone skin gel or ointment is systemically absorbed with once daily dosing; absorption of the gel and solution from the skin occurs continually over the 24 hour dosing interval, which indicates that the skin acts as a reservoir for sustained-release. Application of testosterone solution or gel delivers physiologic circulating testosterone that resembles normal concentration range seen in healthy men.45 Steady-state concentrations are achieved after approximately 14 days of solution application; when the solution is stopped, pre-treatment testosterone concentrations are achieved in approximately 7 to 10 days

• Testosterone is a substrate for hepatic cytochrome P450 (CYP) 3A4 isoenzyme.22 Testosterone is also both transported by and an inhibitor of P-glycoprotein transport.23
• Testosterone can increase the anticoagulant action of warfarin.24 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 recommended, 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 testosterone 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.29
• Goserelin30 and leuprolide31 inhibit steroidogenesis. Concomitant use of androgens with goserelin or leuprolide is relatively contraindicated and would defeat the purpose of goserelin or leuprolide therapy.

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 blood work drawn while on testosterone. This medication is banned from use in athletes by most athletic organizations. 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 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.7 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.8 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. 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. Health care professionals are urged to carefully consider whether the benefits of treatment are likely to exceed the potential risks. 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 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.14 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.215161718 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.7 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.  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.8 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. 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.

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.

Testosterone topical solution, transdermal patches, and gels are contraindicated in lactating women who are breast-feeding.82 It is recommended that other testosterone formulations be avoided during breast-feeding as well.1912 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.20 Historically, testosterone/androgens have been used adjunctively for lactation suppression.20 Alternative methods to breast-feeding are recommended in lactating women receiving testosterone therapy.

Male patients can experience feminization during prolonged therapy with testosterone, which is believed to result from inhibition of gonadotropin secretion and conversion of androgens to estrogens. These effects are more pronounced in male patients with concurrent hepatic disease and include mastalgia and gynecomastia.Feminizing effects of testosterone are generally reversible. Testosterone therapy can produce libido decrease or libido increase.  In clinical evaluation of testosterone gel (Androgel), libido decrease was reported in 1—3% of patients. Priapism and excessive sexual stimulation, more common in geriatric males, are generally the effect of excessive testosterone dosage. Prostatic hypertrophy may develop during prolonged therapy with testosterone and these events are more likely to occur in elderly male patients. In patients receiving testosterone therapy, surveillance for prostate cancer (as a secondary malignancy) should be consistent with current practices for eugonadal men. Signs of acute epididymitis (e.g., pyrexia, pain in the inguinal region) and/or urinary urgency should prompt withdrawal of the drug and reevaluation of dosage. When androgens are given to females, virilization, manifested by acne, the growth of facial hair or an unwanted excess of body hair (hirsutism), enlarged clitoris, reduced breast size, and deepening of the voice, can occur. If testosterone treatment is discontinued when these symptoms first appear, they usually subside. Dermatologic reactions reported post-approval or in < 1% of patients using testosterone gel, regardless of brand, included hirsutism.  Prolonged treatment can lead to irreversible masculinity, so the benefit of treatment should be measured against the risk.151218 Disruption of the regular menstrual cycle secondary to testosterone-induced suppression of gonadotropin secretion can lead to amenorrhea or oligomenorrhea. Topical testosterone products are associated with application site skin reactions. Application site adverse events reported include: pruritus (17—37%), burn-like blister reaction under system (12%), erythema (< 7%), exfoliation (< 3%), vesicular rash (6%), allergic contact dermatitis to the system (4%), burning (3%), and induration (3%); general rash (unspecified) (2%) was also reported. Mild skin irritation may be ameliorated by treatment of affected skin with over-the-counter topical hydrocortisone cream applied after transdermal system removal.  Contact dermatitis was reported in 2.1% of patients treated with testosterone gel (Androgel 1.62%).51 All testosterone therapy influences the growth and secretion of the sebaceous glands, which can cause seborrhea and acne indistinguishable from acne vulgaris. Androgen therapy has been associated with retention of sodium, chloride, water, potassium, and inorganic phosphates.1218 Peripheral edema can occur as the result of increased fluid retention (in association with sodium chloride) and may be manifested by weight gain. These effects may be more prominent earlier in androgen therapy. If normal therapeutic testosterone doses are used in the treatment of hypogonadism, only a moderate amount of fluid retention occurs. In the treatment of patients with impaired renal function or congestive heart failure, the fluid retention is of greater significance. Abnormal dreams and insomnia have been reported in patients receiving testosterone gel. Hot flashes or flushing and asthenia (weakness) were also reported for patients receiving testosterone.  Discontinue treatment with testosterone in patients reporting pain, swelling, warmth, and redness in the leg (DVT) or chest pain, trouble breathing, and cough (PE) and examine for possible VTE.

Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.