Pharmacokinetics of Testosterone Gel for Hypogonadism
The objective of this study was to assess drying time after application of testosterone 2% gel (Fortesta Gel, Endo Pharmaceuticals), time needed for serum total testosterone (TT) to reach the eugonadal range (≥300 ng dl), and time to steady-state serum TT. Thirty-four men with primary or secondary hypogonadism were enrolled in the study; 31 men were included in the pharmacokinetics (PKs) population. Testosterone 2% gel (40 mg) was applied once daily in the morning to the front and inner thighs for 14 days. Median gel drying time was 2.4 min (95% confidence interval (CI), 1.7–3.4 min; n=31). Serum TT concentrations reached the target eugonadal range with a median time of 2.9 h (95% CI, 1.9–4.3 h; n=24). Median time to steady-state serum TT concentration was 1.1 days (95% CI, 0.7–3.4 days; n=31). Six patients (17.6%; n=34) reported treatment-related adverse events; all were mild. The results from this 14-day PK study in men with hypogonadism suggest that testosterone 2% gel dries, on average, in <3 min after application and that testosterone 2% gel rapidly reaches the target eugonadal range and attains steady-state serum TT concentrations in about 1 day.
Male hypogonadism is caused by a dysfunctional hypothalamic–pituitary–testicular axis, resulting in subphysiologic testosterone concentrations. Hypogonadism is diagnosed in men based on the presence of characteristic symptoms (for example, decreased sexual desire, visceral weight gain and increased body mass index) in association with low serum testosterone concentrations. No absolute consensus exists regarding the diagnostic lower limit of normal serum testosterone concentration, but generally, symptomatic men with total testosterone (TT) <300 ng dl are considered to have hypogonadism.
Hypogonadism may be associated with several serious comorbidities. An epidemiologic study in 2650 primary-care practices demonstrated a connection between hypogonadism and multiple comorbidities, including diabetes, cardiovascular risk factors (for example, hypertension and hyperlipidemia), obesity, asthma/chronic obstructive pulmonary disease and prostate disease. These findings are supported by several meta-analyses of prospective and cross-sectional studies, which showed a positive correlation between hypogonadism and metabolic syndrome, type 2 diabetes and cardiovascular mortality.
Testosterone therapy is routinely used for the treatment of hypogonadism. This therapy treats the presenting symptoms by restoring testosterone concentration to the normal (that is, eugonadal) range; clinical efficacy and safety of testosterone therapy are well established. The goals of testosterone therapy are to treat the symptoms of hypogonadism and to achieve and maintain eugonadal testosterone levels. To accomplish these goals, testosterone therapy must be individualized to meet each patient's needs, which may require dose adjustments and multiple consultations with the patient to monitor and encourage regimen adherence.
Testosterone therapy is available in injectable, implantable, buccal, oral and topical (for example, liquid and gel) formulations. Gels result in stable serum testosterone concentrations within the normal range; they are noninvasive, generally well tolerated, and associated with a low risk of skin irritation. Testosterone gel is applied to the skin and is absorbed and stored in the outermost layer of the epidermis, where it is slowly transported into the body's circulation over several hours, mimicking the action of a sustained-release delivery system. Nonetheless, all testosterone gels can pose the risk of transference to other individuals in contact with the man's skin.
In the authors' opinion and clinical experience, daily gel application can be disruptive to a patient's routine. In theory, a higher concentration product should be more convenient because of lower volume of gel for the same dosage, and therefore should contribute to compliance and continued use. Any other product characteristics that improve convenience, such as rapid drying time, should also contribute to adherence and continued use.
The aim of this study was to explore three characteristics of testosterone 2% gel (Fortesta Gel, Endo Pharmaceuticals, Malvern, PA, USA) in men with hypogonadism: gel drying time after application, time to eugonadal TT concentration and time to steady-state TT concentration. Results from an earlier study in 149 men with hypogonadism using this same testosterone 2% gel showed that 78% of patients had TT concentrations within the normal range on day 90; however, time to target eugonadal range, steady state and gel drying time were not evaluated. This study was designed to complement the previous study by providing practical information for the prescribing clinician.
Abstract and Introduction
Abstract
The objective of this study was to assess drying time after application of testosterone 2% gel (Fortesta Gel, Endo Pharmaceuticals), time needed for serum total testosterone (TT) to reach the eugonadal range (≥300 ng dl), and time to steady-state serum TT. Thirty-four men with primary or secondary hypogonadism were enrolled in the study; 31 men were included in the pharmacokinetics (PKs) population. Testosterone 2% gel (40 mg) was applied once daily in the morning to the front and inner thighs for 14 days. Median gel drying time was 2.4 min (95% confidence interval (CI), 1.7–3.4 min; n=31). Serum TT concentrations reached the target eugonadal range with a median time of 2.9 h (95% CI, 1.9–4.3 h; n=24). Median time to steady-state serum TT concentration was 1.1 days (95% CI, 0.7–3.4 days; n=31). Six patients (17.6%; n=34) reported treatment-related adverse events; all were mild. The results from this 14-day PK study in men with hypogonadism suggest that testosterone 2% gel dries, on average, in <3 min after application and that testosterone 2% gel rapidly reaches the target eugonadal range and attains steady-state serum TT concentrations in about 1 day.
Introduction
Male hypogonadism is caused by a dysfunctional hypothalamic–pituitary–testicular axis, resulting in subphysiologic testosterone concentrations. Hypogonadism is diagnosed in men based on the presence of characteristic symptoms (for example, decreased sexual desire, visceral weight gain and increased body mass index) in association with low serum testosterone concentrations. No absolute consensus exists regarding the diagnostic lower limit of normal serum testosterone concentration, but generally, symptomatic men with total testosterone (TT) <300 ng dl are considered to have hypogonadism.
Hypogonadism may be associated with several serious comorbidities. An epidemiologic study in 2650 primary-care practices demonstrated a connection between hypogonadism and multiple comorbidities, including diabetes, cardiovascular risk factors (for example, hypertension and hyperlipidemia), obesity, asthma/chronic obstructive pulmonary disease and prostate disease. These findings are supported by several meta-analyses of prospective and cross-sectional studies, which showed a positive correlation between hypogonadism and metabolic syndrome, type 2 diabetes and cardiovascular mortality.
Testosterone therapy is routinely used for the treatment of hypogonadism. This therapy treats the presenting symptoms by restoring testosterone concentration to the normal (that is, eugonadal) range; clinical efficacy and safety of testosterone therapy are well established. The goals of testosterone therapy are to treat the symptoms of hypogonadism and to achieve and maintain eugonadal testosterone levels. To accomplish these goals, testosterone therapy must be individualized to meet each patient's needs, which may require dose adjustments and multiple consultations with the patient to monitor and encourage regimen adherence.
Testosterone therapy is available in injectable, implantable, buccal, oral and topical (for example, liquid and gel) formulations. Gels result in stable serum testosterone concentrations within the normal range; they are noninvasive, generally well tolerated, and associated with a low risk of skin irritation. Testosterone gel is applied to the skin and is absorbed and stored in the outermost layer of the epidermis, where it is slowly transported into the body's circulation over several hours, mimicking the action of a sustained-release delivery system. Nonetheless, all testosterone gels can pose the risk of transference to other individuals in contact with the man's skin.
In the authors' opinion and clinical experience, daily gel application can be disruptive to a patient's routine. In theory, a higher concentration product should be more convenient because of lower volume of gel for the same dosage, and therefore should contribute to compliance and continued use. Any other product characteristics that improve convenience, such as rapid drying time, should also contribute to adherence and continued use.
The aim of this study was to explore three characteristics of testosterone 2% gel (Fortesta Gel, Endo Pharmaceuticals, Malvern, PA, USA) in men with hypogonadism: gel drying time after application, time to eugonadal TT concentration and time to steady-state TT concentration. Results from an earlier study in 149 men with hypogonadism using this same testosterone 2% gel showed that 78% of patients had TT concentrations within the normal range on day 90; however, time to target eugonadal range, steady state and gel drying time were not evaluated. This study was designed to complement the previous study by providing practical information for the prescribing clinician.
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