|Year : 2018 | Volume
| Issue : 2 | Page : 34-37
Factors affecting adherence to testosterone replacement therapy
Abdullah Gul1, Emrah Yuruk2, Mehmet Gokhan Culha3, Ege Can Serefoglu2, Ahmet Yaser Muslumanoglu2
1 Department of Urology, The Ministry of Health, University of Health Sciences, Van Education & Research Hospital, Van, Turkey
2 Department of Urology, The Ministry of Health, University of Health Sciences, Bagcilar Training and Research Hospital, Istanbul, Turkey
3 Department of Urology, The Ministry of Health, University of Health Sciences, Okmeydani Training and Research Hospital, Istanbul, Turkey
|Date of Submission||20-Mar-2018|
|Date of Acceptance||13-May-2018|
|Date of Web Publication||27-Jun-2018|
Dr. Abdullah Gul
Department of Urology, The Ministry of Health, University of Health Sciences, Van Education & Research Hospital, Van 65100
Source of Support: None, Conflict of Interest: None
Aim: There are several treatment modalities for testosterone replacement therapy (TRT), including topical gels, subcutaneous testosterone pellets, transdermal patches, intramuscular injectables and oral forms. Despite the increasing usage of testosterone, there is limited information concerning patient adherence and compatibility of TRT. The aim of this study is to evaluate the factors which may have an impact on patients' adherence to TRT with topical gel. Methods: Between January 2013 and September 2013, 60 men from a tertiary urology clinic, who were prescribed 50 mg testosterone topical gel, were telephonically contacted to know if they continued or discontinued TRT, and when discontinued, the reasons for the same. Results: The mean age of the patients was 40.9 ± 9.9 (range: 21–59) years. The participation rate for the study through telephone was 51.6% (31/60). The most common reason for discontinued TRT was lack of perceived efficacy [n = 11 (35.5%)]. Factors, including age, weight, height, relationship status, and presence of comorbidity, were not associated with TRT adherence. The mean (standard error) time to TRT withdrawal was 5.9 (0.9) months. Conclusion: Most men voluntarily decided to discontinue testosterone and thus a close monitoring of patients by clinicians is essential to increase TRT adherence rate, with testosterone topical gel.
Keywords: Hypogonadism, medical adherence, testosterone replacement therapy, topical testosterone gel
|How to cite this article:|
Gul A, Yuruk E, Culha MG, Serefoglu EC, Muslumanoglu AY. Factors affecting adherence to testosterone replacement therapy. Transl Surg 2018;3:34-7
|How to cite this URL:|
Gul A, Yuruk E, Culha MG, Serefoglu EC, Muslumanoglu AY. Factors affecting adherence to testosterone replacement therapy. Transl Surg [serial online] 2018 [cited 2019 Dec 7];3:34-7. Available from: http://www.translsurg.com/text.asp?2018/3/2/34/235394
| Introduction|| |
Hypogonadism (HG) in a male is encountered when at least two properly measured serum testosterone levels fail to reach/exceed normal values. Moreover, symptom and signs related to low testosterone levels should also be noted to make the diagnosis. The most common signs and symptoms reported are low libido, decreased energy, increased fatigability, decreased strength and endurance, mood changes, and bone density loss.,, Although epidemiological studies providing the exact prevalence of male HG are lacking, it has been shown that HG is more common among elderly men. In one survey by Araujo et al., the crude prevalence of symptomatic HG was reported to be around 6% in middle aged to older men. Although the prevalence of HG increased with age, waist circumference, and poor self-reported health status, no relation was established with race and ethnicity. It is estimated that HG is an underdiagnosed medical condition affecting almost 5 million men in the USA., Although HG is most commonly seen in the older population, it is not a disease of the elderly and can also be seen in younger men with sexual dysfunction or infertility.
For symptomatic men with HG, Endocrine Society Clinical Practice Guidelines recommends testosterone replacement therapy (TRT) to induce and maintain secondary sex characteristics and to improve their sexual function, sense of well-being, muscle mass and strength, and bone mineral density. The recognition of the clinicopathological consequences of testosterone deficiency and increased awareness of the patients with the help of the pharmaceutical industry-supported advertisements resulted in increased number of patients seeking treatment for HG. From 2001 to 2011, androgen use among men (40 years or older) increased >3-fold (from 0.81% in 2001 to 2.91% in 2011) in the USA.
The most common form of TRT used for treatment of HG in the USA is topical gels due to their noninvasive, once daily, and easy application.,, Although TRT with topical gels has been shown to be effective in both normalizing the testosterone levels and decreasing the symptoms, little is known about patient adherence to treatment and factors affecting the discontinuation and patient level data. The purpose of this study is to evaluate the factors which may have an impact on patients' adherence to TRT and to improve treatment success and patients' quality of life.
| Methods|| |
Study population and design
The study was conducted with the approval of the Institutional Review Board (IRB) of the Bagcilar Training and Research Hospital (IRB No. 2014-229). Data of patients who were diagnosed with low serum testosterone levels together with symptoms consistent with HG, and initiated TRT between January and September of 2013 were collected retrospectively from the hospital database. Only patients to whom the same trademark (Testogel ®, Bayer Turkey, Istanbul, Turkey) was prescribed were included, while patients who switched to other topical treatments or to a systemic agent and the patients who did not want to be involved in the study were excluded. The cut-off value of serum testosterone level was 230 ng/dL.
Patient demographics, presence of comorbidities, relationship status (married, with a stable partner, without a stable partner), presence of the symptoms, and serum testosterone levels were recorded.
Patients were telephonically surveyed by a urology resident (AG) at least 3 months apart from the first prescription of the drug. After receiving verbal approval, participants were asked if they still continued to use the drug, and if discontinued, detailed reasons for the same were also asked using an open ended question –“Why did you stop using the drug and did you stop the drug with a doctor's advice or visit?” Moreover, we asked for “adverse effects” as a cause of drug discontinuation.
The Kolmogorov–Smirnov test was applied to examine the normality of the distribution. Variables were expressed as the means and standard deviations. In addition, independent t- test, Kaplan–Meier estimation, and Pearson correlations were applied for analyses involving variables. All statistical analysis was performed with SPSS V17.0 (SPSS Inc., Chicago, IL, USA). A two-sided P < 0.05 was considered statistically significant.
| Results|| |
During the study period, TRT was initiated in a total of 60 patients whose demographic characteristics are listed in [Table 1]. Of these, 31 patients consented to participate in the study and answered the questions, the data of whom were considered for further analyses. Baseline total testosterone levels were below normal in 49 (81.6%) patients. TRT was initiated despite normal total testosterone levels in 9 (15%) patients since they had symptoms of HG and total testosterone levels being close to the lower normal range.
|Table 1: Baseline characteristics and demographic statistic for all patients|
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The study participation rate was 51.6% (31/60), within which the drug adherence rate was only 22.6% (7 patients out of 31). The most common reason for drug discontinuation was lack of symptomatic efficacy and was reported by 35.5% (11/31) of the patients. Other reasons for drug discontinuation were self-decision due to sufficient response and thus no more necessity for the treatment (29%) and physician's recommendation to stop the treatment (12.9%) [Table 2]. None of the patients reported adverse effects as a cause of drug discontinuation. Of the 31 participants, 4 (12.9%) reported drug application to penile shaft. Inappropriate application, on the other hand, did not affect the drug adherence.
Patients' age, weight, height, relationship status, and the presence of comorbidities were not associated with adherence to TRT [Table 3]. While the longest duration of TRT usage was 2 years, the shortest one was 1 month. Kaplan–Meier estimation revealed that the mean drug discontinuation duration was 5.9 ± 0.9 months.
| Discussion|| |
Although an increasing number of men are using TRT, there are both limited information and incompatible results about adherence to therapy. While many of the studies found high adherence rates, only a few studies revealed lower rates like ours. Adherence rates with follow-up periods in such similar studies are shown in [Table 4]. The most interesting finding of the current study is that only 7 (22.6%) patients were continuing the TRT. The wide variety of adherence rates reported in the literature can be linked to the inclusion of heterogeneous TRT formulations, the discontinuation criteria used, the number of patients included, socioeconomic status of the participants, and the difference in study designs.
|Table 4: Studies evaluating adherence rates to testosterone replacement therapy|
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Consistent with the previous reports,, lack of symptomatic efficacy (35.5%) was found to be the most common reason of drug discontinuation in our study. Unfortunately, these patients did not come to follow-up visits, and therefore, the reasons for insufficient efficacy were not asked, and their post-treatment testosterone levels were thus not checked. However, such rapid cessation of the therapy may be related to the insufficient/improper patient information regarding the time course of symptom relief or the expected degree of symptom relief.
The second most common reason was the self-decided symptomatic relief (29.9%). A current meta-analysis revealed that TRT improves the quality of life significantly in patients with late-onset HG. In addition to the overall score, TRT also improves the psychological, somatic, and sexual subscales. Therefore, it is not surprising that the majority of the patients who discontinued the treatment reported beneficial effects of the drug. Unfortunately, the patients in our study cohort discontinued the treatment because of the positive effects without any doctor consent. Furthermore, the effects of cessation of TRT in these patients were not evaluated. However, it has been reported that even after a long period of TRT, cessation of the therapy results in aggravation of the symptoms. Both patients reported reasons for drug cessation highlight the importance of the patient information and communication to clarify the possible treatment and complication rates of the given regimen and also the duration of the treatment in responders.
Regarding the currently available literature, another important cause of treatment interruption/cessation is the drug-related adverse events. Interestingly, none of the patients in the current study group reported drug-related adverse effects. Complications were not reported even in patients (12.9%) who applied the drug to penile shaft. This may be partly explained by the study design, i.e., we only asked the reasons of drug discontinuation during the interview and did not take detailed history regarding the complications or make detailed laboratory analysis including serum hemoglobin and lipid levels.
Insurance-related problems have also been reported as the primary cause of drug discontinuation. Lack of insurance may further facilitate the cessation of drug despite the status of drug effectiveness. However, the health system in Turkey is completely free of charge and covers all the patients in the current study and thus excluding the insurance-related problem as a reason of drug discontinuation.
Age of the patient is a well-described factor affecting the adherence to the therapy. Relatively younger mean age of the study cohort may explain the lower adherence rate to the TRT. However, when we only take the younger age groups into account, our TRT adherence rates are not so different from the previously published series.,,,, The lower adherence rate may also be linked to the different formulations used in the previous series. A recent Canadian study demonstrated that the adherence rates differed significantly among different formulations with oral products having the longest duration of use.
The effects of TRT on sexual desire appear as early as 3 weeks and plateaus at 6 weeks, while improvements in erectile function are reported at the end of 3rd month. As the erectile dysfunction was the most common presenting symptom among the participants, early drug discontinuation can easily be linked to this early effects of the TRT.
The current study has several limitations. First, the objective symptom scores including International Index of Erectile Function and Aging Males' Symptoms of the participants were not obtained before the treatment or at the end of the study. Therefore, the real symptomatic effect of the treatment cannot be documented. Small sample size and short follow-up period are other limitations. Moreover, since the patients who did not experience any symptomatic relief stopped therapy without doctor visit, serum testosterone levels of them were not recorded.
In conclusion, the high-drug discontinuation rate without doctor recommendation and visit in the current study indicate the need for physicians to closely follow-up with their patients to improve the TRT adherence rate and patients' satisfaction.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dean JD, McMahon CG, Guay AT, Morgentaler A, Althof SE, Becher EF, Bivalacqua TJ, Burnett AL, Buvat J, El Meliegy A, Hellstrom WJ, Jannini EA, Maggi M, McCullough A, Torres LO, Zitzmann M. The international society for sexual medicine's process of care for the assessment and management of testosterone deficiency in adult men. J Sex Med
Hall SA, Esche GR, Araujo AB, Travison TG, Clark RV, Williams RE, McKinlay JB. Correlates of low testosterone and symptomatic androgen deficiency in a population-based sample. J Clin Endocrinol Metab
Araujo AB, O'Donnell AB, Brambilla DJ, Simpson WB, Longcope C, Matsumoto AM, McKinlay JB. Prevalence and incidence of androgen deficiency in middle-aged and older men: Estimates from the Massachusetts male aging study. J Clin Endocrinol Metab
Bhasin S, Basaria S. Diagnosis and treatment of hypogonadism in men. Best Pract Res Clin Endocrinol Metab
Araujo AB, Esche GR, Kupelian V, O'Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB. Prevalence of symptomatic androgen deficiency in men. J Clin Endocrinol Metab
Travison TG, Araujo AB, O'Donnell AB, Kupelian V, McKinlay JB. A population-level decline in serum testosterone levels in American men. J Clin Endocrinol Metab
Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR; Baltimore Longitudinal Study of Aging. Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab
Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS, Montori VM; Task Force, Endocrine Society. Testosterone therapy in men with androgen deficiency syndromes: An endocrine society clinical practice guideline. J Clin Endocrinol Metab
Baillargeon J, Urban RJ, Ottenbacher KJ, Pierson KS, Goodwin JS. Trends in androgen prescribing in the United States, 2001 to 2011. JAMA Int Med
Swerdloff RS, Wang C, Cunningham G, Dobs A, Iranmanesh A, Matsumoto AM, Snyder PJ, Weber T, Longstreth J, Berman N. Long-term pharmacokinetics of transdermal testosterone gel in hypogonadal men. J Clin Endocrinol Metab
McNicholas TA, Dean JD, Mulder H, Carnegie C, Jones NA. A novel testosterone gel formulation normalizes androgen levels in hypogonadal men, with improvements in body composition and sexual function. BJU Int
Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R; North American AA2500 T Gel Study Group. AA2500 testosterone gel normalizes androgen levels in aging males with improvements in body composition and sexual function. J Clin Endocrinol Metab
Malik RD, Wang CE, Lapin B, Lakeman JC, Helfand BT. Characteristics of men undergoing testosterone replacement therapy and adherence to follow-up recommendations in metropolitan multicenter health care system. Urology
Rhoden EL, Morgentaler A. Symptomatic response rates to testosterone therapy and the likelihood of completing 12 months of therapy in clinical practice. J Sex Med
Smith RP, Khanna A, Coward RM, Rajanahally S, Kovac JR, Gonzales MA, Lipshultz LI. Factors influencing patient decisions to initiate and discontinue subcutaneous testosterone pellets (Testopel) for treatment of hypogonadism. J Sex Med
Nian Y, Ding M, Hu S, He H, Cheng S, Yi L, Wang Y. Testosterone replacement therapy improves health-related quality of life for patients with late-onset hypogonadism: A meta-analysis of randomized controlled trials. Andrologia
Yassin AA, Nettleship J, Almehmadi Y, Salman M, Saad F. Effects of continuous long-term testosterone therapy (TTh) on anthropometric, endocrine and metabolic parameters for up to 10 years in 115 hypogonadal elderly men: Real-life experience from an observational registry study. Andrologia
Hajjar RR, Kaiser FE, Morley JE. Outcomes of long-term testosterone replacement in older hypogonadal males: A retrospective analysis. J Clin Endocrinol Metab
Schoenfeld MJ, Shortridge E, Cui Z, Muram D. Medication adherence and treatment patterns for hypogonadal patients treated with topical testosterone therapy: A retrospective medical claims analysis. J Sex Med
Bhattacharya RK, Khera M, Blick G, Kushner H, Miner MM. Testosterone replacement therapy among elderly males: The Testim Registry in the US (TRiUS). Clin Interv Aging
Martins D, Yao Z, Tadrous M, Shah BR, Juurlink DN, Mamdani MM, Gomes T; Ontario Drug Policy Research Network. The appropriateness and persistence of testosterone replacement therapy in Ontario. Pharmacoepidemiol Drug Saf
Saad F, Aversa A, Isidori AM, Zafalon L, Zitzmann M, Gooren L. Onset of effects of testosterone treatment and time span until maximum effects are achieved. Eur J Endocrinol
Chiang HS, Cho SL, Lin YC, Hwang TI. Testosterone gel monotherapy improves sexual function of hypogonadal men mainly through restoring erection: Evaluation by IIEF score. Urology
[Table 1], [Table 2], [Table 3], [Table 4]