The Effect of Testosterone on Men With Andropause.

BACKGROUND: Andropause is the gradual reduction of the male sex hormone (testosterone) with increasing age. Its symptoms are sexual dysfunction, weakness, fatigue, insomnia, loss of motivation, mood disorders and reduction of bone density. Treatment of andropause with testosterone has been recently considered.
OBJECTIVES: The aim of this study was to evaluate the effect of testosterone in the treatment of andropause in men. PATIENTS AND METHODS: For men who met the inclusion criteria (50 years of age and older) laboratory tests and clinical examinations were conducted by an urologist in order to diagnose prostate cancer, prostate disease, urinary tract infection and active urinary retention. After obtaining consent, the patients were enrolled in the study. Data were analyzed using SPSS version 20. Descriptive statistics (frequency and percentage, mean, standard deviation) and the paired t-test were used to compare levels of testosterone. To determine the correlation between age and testosterone levels, the Pearson correlation was used. Finally, to compare the treatment processes during the treatment period the repeated measures ANOVA was used.
RESULTS: The mean age of patients was 56.57 ± 3.21 years. A total of 31 patients (39%) were smokers, among them 30% smoked daily, 2.5% weekly and 6% smoked for fun. The mean testosterone level before treatment was 240.6 ± 125.4 and at 1, 3 and 6 months after treatment the level was raised, so that at the end of the sixth months it was 578.7 ± 141.7. The level of increase was statistically significant (P = 0.0001).
CONCLUSIONS: Treatment with testosterone in men over 50 years with andropause will increase testosterone levels and also quality of life, sexual desire, erection, energy levels, ability to exercise and feel the joy of life more than before. Depression was decreased and they had sleepy feelings after dinner.

1. Background

Testosterone is responsible for secondary sex characteristics, sexual desire and erection. Also, it increases metabolic processes in the muscles, bones, bone marrow, immune system and brain (1). Therefore, a reduction in the level of testosterone leads to symptoms that are caused by the decrease of these processes. Total testosterone levels in men consist of three parts: (a) testosterone that binds strongly to SHBG (sex hormone binding globulin); this accounts for almost 80% of total testosterone and serves as a reserve source; (b) testosterone also binds to albumin, but this binding is weak and easily available; (c) and free testosterone (2). Free testosterone and testosterone bound to albumin are biologically active and are 20% of total testosterone (2, 3). Testosterone levels in men aged 40 is reduced (4), and the total testosterone level is reduced 0.3% annually (5, 6). The average amount of testosterone in men of 75 years of age is 66% of men aged 25 (6-8). The decline of testosterone levels with aging, on one hand, is related to testis dysfunction (Leydig cell mass reduction, a decrease in performance of the remaining cells, as well as reduced testis circulation), and on the other hand, to reduced testosterone-stimulating hormones, including GnRH from the hypothalamus and gonadotropin from the pituitary gland (5, 9).

Andropause is the gradual reduction of the male sex hormone (testosterone) with increasing age, and its symptoms are sexual dysfunction, weakness, fatigue, insomnia, loss of motivation, mood disorders and reduction of bone density (10). Recently, andropause treatment with testosterone has been considered. The serum level of testosterone is different in individuals, however, in most experiments 10 nmol/L to 35 nmol/L has been found to be within the normal range (2). One of the issues facing older people is finding the lower level of testosterone that causes andropause (11). So, to diagnosis andropause, in addition to testosterone serum levels, clinical symptoms should be considered (12). Besides considering the possible benefits of testosterone therapy in older men for andropause treatment, possible complications including benign prostatic hyperplasia, prostate cancer, exacerbation of sleep apnea, gynecomastia, polycythemia and liver toxicity should be considered (12, 13).

Andropause has been widely considered in recent years by the medical societies (14). Some studies of testosterone therapy have mentioned significant progress in reducing the symptoms (11, 15). However, the benefit of testosterone therapy in this age group still faces uncertainty (16).

Because there are few studies in our country (Iran) about andropause and testosterone therapy in men over 50 years of age, the results of this study are important in the treatment of men with andropause.

2. Objectives

The aim of this study is to evaluate the effect of testosterone in the treatment of andropause in men.

3. Patients and Methods

This study was conducted as a before-after study. The study population included 80 men over fifty years old, who were referred to the private office of the researcher in 2014 in Sanandaj, Iran. Exclusion criteria included suspicion of having prostate cancer, prostate disease, urinary tract infection and the risk of active urinary retention. Before starting the study, serum testosterone levels of the men were measured by radio immunoassay and the ADAM (Androgen Deficiency in the Aging Male) questionnaire was completed via interview. Men who had inclusion criteria were enrolled after obtaining informed consent.

The ADAM questionnaire consists of 10 questions with yes or no answers. In this questionnaire the answer of “yes” to questions 1 or 7, or the answer of “yes” to three questions from questions 8 to 10, confirmed testosterone deficiency. If the answer to questions 1 or 7 and questions 8 to 10 were negative, then the patient was considered healthy.

The men were treated with Testocaps capsules manufactured by Schering-Plough, with one 40 mg capsule per day for a period of six months. At the end of months 1, 3 and 6 after the intervention, serum testosterone levels were measured and the ADAM questionnaire was completed again, simultaneously. Based on the ADAM questionnaire results and the serum testosterone levels of the men, treatment of andropause was determined by an urologist and recorded in a checklist.

Data were analyzed using SPSS version 20. Descriptive statistics (frequency and percentage, mean, standard deviation) and paired t-test were used to compare levels of testosterone. To determine the correlation between age and testosterone levels, the Pearson correlation was used. Finally to compare the treatment process during the treatment period the repeated measures ANOVA was used.

4. Results

The mean age of patients was 56.57 ± 3.21 years, with an age range of 51 - 67 years. Of the total, 70% were urban dwellers, 38% were smokers and 20% used alcohol. Also, 17.5% had an underlying chronic disease such as hypertension or diabetes (Table 1).

Table 1.

The Frequency of Variables in Men With Andropause[a]

Variable	Values
Education
Illiterate	9 (8.7)
Literate	71 (92.3)
Occupation
Employee	34 (42.5)
Business	22 (27.5)
Farmer	14 (17.5)
Army	10 (12.5)
Dwelling
City	56 (70)
Village	24 (30)
Smoking
Yes	31 (37.7)
No	49 (61.3)
Alcohol
Yes	16 (20)
No	64 (80)
Underlying medical condition
Yes	14 (17.5)
No	66 (82.5)
Use of other medicines
Yes	13 (16.3)
No	67 (83.7)

aValues are presented as No. (%).

Analyzing the ADAM questionnaire before the treatment stage, 100% of patients had andropause. After the first month of treatment, the andropause rate was 87.5%, and in the third month it was 55%. It reached 0% after six months (Table 2).

Table 2.

Prevalence of Symptoms Before and After Treatment in Men With Andropause, Based on the ADAM Questionnaire[a]

ADAM Questionnaire Questions	Before Treatment	1 Month After Treatment	3 Months After Treatment	6 Months After Treatment
Decrease in sexual desire and cold tempered
Yes	80 (100)	41 (51.2)	2 (2.5)	0
No	0	39 (48.8)	78 (97.5)	80 (100)
Decreased energy levels
Yes	71 (88.7)	61 (76.2)	41 (51.2)	10 (12.5)
No	9 (11.3)	19 (23.8)	39 (48.8)	70 (87.5)
Reduced power and physical endurance
Yes	68 (85)	62 (77.5)	50 (62.5)	16 (20)
No	12 (15)	18 (22.5)	30 (37.5)	64 (80)
Height loss
Yes	21 (26.2)	20 (25)	33 (41.2)	21 (26.3)
No	59 (73.8)	60 (75)	47 (58.8)	59 (73.7)
Reduced feeling of joy of life
Yes	76 (95)	70 (87.5)	29 (36.3)	10 (12.5)
No	4 (5)	10 (12.5)	51 (63.7)	70 (87.5)
Feelings of depression and bad moral
Yes	57 (71.3)	48 (60)	31 (38.7)	10 (12.5)
No	23 (28.7)	32 (40)	49 (61.3)	70 (87.5)
Reduced strength and durability of erection of the penis
Yes	79 (98.8)	78 (97.5)	41 (51.2)	0
No	1 (1.2)	2 (2.5)	39 (48.8)	80 (100)
Reduced sport power
Yes	70 (87.5)	62 (77.5)	56 (70)	32 (40)
No	10 (12.5)	18 (22.5)	24 (30)	48 (60)
Feeling sleepy after Dinner
Yes	39 (48.8)	30 (38)	22 (27.5)	7 (8.8)
No	41 (51.2)	50 (62.5)	58 (72.5)	73 (91.2)
Reduced performance
Yes	64 (80)	58 (72.5)	47 (58.8)	13 (16.3)
No	16 (20)	22 (27.5)	33 (41.2)	67 (83.7)
Total
Yes	80 (100)	70 (87.5)	44 (55)	0
No	0	10 (12.5)	36 (45)	80 (100)

aData are presented as No. (%).

Testosterone levels in the subjects before treatment was 240.6 nmol/L, and at the end of months one, three and six after the intervention the trend was positive. At the end of the sixth month, the average of testosterone levels was 578.7 nmol/L. Based on repeated measures ANOVA data, this increase of testosterone levels was statistically significant (P = 0.0001) (Table 3). The findings also showed that there is a significant and inverse correlation between age and testosterone levels before and after the treatment, namely, the level of testosterone is reduced with increasing age (Table 4).

Table 3.

Comparison of Testosterone Levels Before and After Treatment in Men With Andropause

Testosterone Levels	Values[a]	Confidence Interval 95%	P Value
Before treatment	240.6 ± 24.5	246.3 - 235	0.0001 F[b] = 3202.1
1 Month after treatment	285.5 ± 30.6	292.3 - 278.6	0.0001 F[b] = 3202.1
3 Months after treatment	370.5 ± 75.1	387.1 - 353.6	0.0001 F[b] = 3202.1
6 Months after treatment	578.7 ± 141.7	610.2 - 547.1	0.0001 F[b] = 3202.1

aValues are presented as men ± SD.

bRepeated measures ANOVA.

Table 4.

The Correlation Between Testosterone Levels With Age Before and After Intervention in Men Under Study

Testosterone levels	r	P Value
Before treatment	-0.38	0.0001
1 Month after treatment	-0.45	0.0001
3 Months after treatment	-0.49	0.0001
6 Months after treatment	-0.54	0.0001

5. Discussion

In our study, oral administration of testosterone increased testosterone levels in men over 50 years who were suffering from andropause. Over time, there was no need to increase the dose of medicine to constant changes in testosterone levels and clinical symptoms.

In a study by Ko et al. (16), oral administration of testosterone decanoate had an effect in the short term, but its effect was low. In the treatment procedure, serum testosterone levels are rarely kept higher than average levels. In a study by Bae et al., intramuscular injection of testosterone had a greater impact than oral use and increased the levels of testosterone in men with andropause (17).

In another study, Bae et al. found that men who consumed testosterone pills with meals had higher serum testosterone levels than those who consumed the pill after meals (18). In a study by Tan et al., testosterone therapy increased the strength and durability of erection and improved sexual performance of men with andropause (19). Also, in a study by Legros et al. testosterone therapy improved sexual performance (20).

The aim of Ronald`s study was increasing the level of testosterone in men with andropause to a normal range of 400 - 700 ng/dL, and also reducing the symptoms of andropause (21). In this study, at the end of the intervention, testosterone levels reached 578 ng/dL, and the symptoms of andropause were reduced. Also in this study, there was an inverse relationship between age and testosterone levels. Testosterone levels in all stages of treatment and at 1, 3 and 6 months after treatment was reduced.

In a study conducted by Michel et al., they showed that with increasing age approximately 20% of the testosterone levels of men by age 60 and 50% of men by age 80 are reduced (22). Changes in testosterone levels in different races may be due to a low-fat diet and high consumption of carbohydrates. Although, dietary protein increases testosterone levels and reduces its age-related effects (23).

In analyzing the ADAM questionnaire before treatment, 100% of patients had androgenesis. After six months it was 0% and all patients had improvement in sexual desire. In a study by Matsumoto et al. (24), testosterone therapy in older men increased muscle strength, physical activity, penile erectile function, libido, cognitive function and quality of sleep, and also reduced depression. In a study by Bae et al., intramuscular injections of testosterone in patients with andropause increased ADAM questionnaire scores, especially sexual desire scores (17). In a study by Zhang et al. (25), six months after the end of treatment the effect of testosterone on increasing the quality of life was observed. In a study by Legros et al., the quality of life of older men was improved with testosterone therapy (20). Also in a review study conducted by Bassil et al. (26), the benefits of testosterone therapy were stated as increased sexual function, bone density, muscle mass, improved mood, quality of life and cognitive function, as well as increase in power. These findings are consistent with the findings of this study.

The use of testosterone therapy increased acne, oily skin, gynecomastia, risk of prostate cancer, cardiovascular disease and lipid changes, and also increased the hematocrit levels (19, 26-28). Of course, to evaluate the risks of using testosterone was not the aim of our study.

Treatment with testosterone in men over 50 years with andropause will increase testosterone levels and also quality of life, sexual desire, erection, energy levels, ability to exercise and feel the joy of life more than before. Depression was decreased and they had sleepy feelings after dinner.