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Original Article

The association between hypogonadism symptoms with serum testosterone, FSH and LH in men

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Pages 1-8 | Received 14 Aug 2017, Accepted 18 Sep 2017, Published online: 06 Oct 2017

Abstract

Objectives: This study aimed to determine the relationship of hypogonadism symptoms with the levels of sex hormones in men.

Methods: This cross-sectional study was conducted on 140 men aged above 40 years. Data collections were conducted by Aging Male Scales (AMS) questionnaire and some sociodemographic variables. Then, 3 ml blood serum was sampled for testosterone (free and total), FSH and LH. Data were analyzed by descriptive and analytical statistics.

Results: Mean age score was 52.09 ± 7.096. There was no significant association between total score of the symptoms of hypogonadism and serum total and free testosterone level while it was shown significant association with BMI (p = .021) and occupation (p = .005).

Conclusion: The most men experienced the symptoms of hypogonadism and the majority of the symptoms were related to psychological domain. The symptoms of hypogonadism are considered to some factors like BMI and occupation too.

1. Introduction

Male hypogonadism is a clinical syndrome resulting from androgen deficiency that may affect on the function of different organs and the quality of life [Citation1]. Male hypogonadism is classified into four groups: (1) Male hypogonadism of gonadal origin (primary hypogonadism); (2) Male hypogonadism of hypothalamic–hypopituitary origin (secondary hypogonadism); (3) Late-onset Hypogonadism (LOH); (4) hypogonadism resulting from androgen target organs (androgen insensitivity/resistance) [Citation2].

Hypogonadism is defined as a syndrome at midlife that is associated with testosterone (free and total) deficiency and sexual symptoms [Citation3]. This deficiency increases with aging that is a complicated and different phenomena [Citation2,Citation4,Citation5]. The age-related decrease in testosterone occurs as a result of insufficiency in all levels of the hypothalamic–pituitary–gonadal axis [Citation6]. It seems that the testes undergo the most important changes, where there is a decrease in the number of Leydig cells [Citation5]. In fact, the serum testosterone levels in men begin to decrease gradually from 40–50 years of age (1–2% per year) [Citation7]. The age-related decrease in testosterone is generally known as andropause/LOH [Citation6].

The prevalence of hypogonadism has increased recently and 12%, 19%, 28% and 49% of men suffer from hypogonadismat 50, 60, 70 and 80 years of age, respectively [Citation4]. Testosterone deficiency in men may be associated with symptoms and sings [Citation8], including sexual and erectile dysfunction, decreased libido, cognitive disorders, irritability, sadness, night sweat, decrease enjoyment of life, decrease in work performance, palpitation, short stature, Sarcopenia, sleepiness after dinner, decreased bone mass, mood disorders, fatigue, anger, sleep disorder, hair loss, flushing, loss of stamina and depression [Citation1–3,Citation6]. One study showed that sexual symptoms appear before nonsexual and psychological symptoms and that the symptoms are associated with general health, health behaviors/actions, life satisfaction and frequency of physician visiting [Citation9]. Sexual dysfunction is the most important symptom of testosterone deficiency for medical consultation [Citation10].

Decreased testosterone for the diagnosis of hypogonadism is usually a borderline parameter. Another parameter that can be used to detect hypogonadism is the measurement of the serum luteinizing hormone (LH) [Citation3]. LH has a direct effect on testosterone secretion through Leydig cells [Citation11]. Hypogonadism can be primary (low testosterone, high LH) resulting from insufficiency of the testes or secondary (low testosterone, low or insufficiency LH) to hypothalamic–pituitary insufficiency [Citation3]. The testosterone levels fluctuate in response to LH pulsatile release. Follicle-stimulating hormone (FSH) has less pulsatility than LH and its increase indicates injury to somniferous tubules [Citation6]. The latest Endocrinology Society Clinical Practice guideline (2010) considers a diagnosis of LOH based on the assessment of clinical symptoms and signs along with the measurement of the testosterone levels [Citation12,Citation13].

Some studies [Citation14–17] indicated that the symptoms of hypogonadism are associated with decreased serum levels of total and free testosterone. While other studies [Citation18,Citation19] were in contrast showed no significant relationship between the symptoms of hypogonadism and serum levels of testosterone.

It seems that the relationship between the symptoms of hypogonadism and levels of testosterone hormone is unclear, which leads to different viewpoints in diagnosis, treatment and control of the symptoms. In fact, the relationship between hypogonadism and levels of testosterone is important in diagnosis, treatment and the assessment of testosterone replacement therapy. This study aimed to clarify the experience of hypogonadism symptoms and their association with sex hormones such as total and free testosterone, FSH and LH.

2. Material and methods

2.1 Participants and procedure

This cross-sectional descriptive-analytical study was conducted on 140 men (out of 240 men agreed to respond the questionnaire) aged above 40 years which they referred to one of the exclusive healthcare centers of Rasht affiliated to Guilan University of Medical Sciences (GUMS).

Inclusion criteria were age above 40 years, and a negative history of psychological and physical diseases. Purposive sampling was performed for 3 months from July to September in 2015 to select the eligible men. First, the objective and protocol of the study was explained to the eligible men and they were told that they could be informed of the study results if they were willing to. Then, only those who signed an informed consent were enrolled into the study voluntarily. By using Cochran’s sample size formula, 140 men were calculated based on a previous study [Citation18] with 95% confidence interval (CI) and precision of 10%.

After the main researcher completed the questionnaire and recorded the participants’ blood pressure, height and weight, 3 ml blood serum was taken from each participant to investigate free and total testosterone, FSH and LH. The blood samples were taken between 9–11 am, for the highest and lowest levels of serum testosterone that is observed in the morning [Citation4] and evening due to effecting of the circadian rhythm on testosterone secretion [Citation20], respectively. All the blood samples were sent to one Laboratory in Rasht within 1 h. Sex hormones were measured with chemiluminescence laboratory kits and ELISA method. The normal limits of total (202–1096 ng/dl) and free (5–31 pg/ml) testosterone, FSH (1.4–15.4 IU/l), and LH (1.2–7.8 IU/l) were defined using the United States scale. Testosterone deficiency was defined as a total testosterone levels below 349 ng/dl. Total testosterone was categorized as low (<200 ng/dl), borderline low (200–350 ng/dl) and normal (>350 ng/dl) [Citation6], and free testosterone was categorized as low (<5 pg/ml) and normal (5–31 pg/ml) according to laboratory criteria.

2.2 Questionnaire

The data collection instrument included two parts. In the first part, there were eight questions regarding demographic characteristics including age, marital status, education, occupation, monthly income, body mass index (BMI), cigarette smokin, and blood pressure. Blood pressure was measured by an ALPK2 aneroid sphygmomanometer after 10 min in the sitting position rest, height was measured with a measuring tape, and weight was measured with a digital scale and the accuracy of 50 g. BMI was based on kg/m2 and categorized to underweight <18.5, normal range: 18.5–24.99, preobese: 25–29.99, obese ≥30 [Citation21].

The second part was the standard questionnaire named Aging Males’ Symptoms (AMS) scale. It has 17 questions in three domains of somatic (questions: 1, 2, 3, 4, 5, 9, 10), psychological (questions: 6, 7, 8, 11, 13) and sexual (questions: 12–17) [Citation22]. Each question was given a score of 1–5 ranged from 5 to 35. A score of 17 indicates lack of the symptoms related to hypogonadism and a score of 85 shows severe symptoms. The severity of the symptoms can be defined as: no/little (17–26 points), mild (27–36 points), moderate (37–49 points) and severe (50 points and higher) [Citation23]. In this study, the Cronbach’s alpha of the AMS scale was 0.85 indicating a high reliability. The validity and reliability of this Scale in Iran were evaluated by Khosravi in 2014 and Cronbach’s alpha of 0.7 was reported [Citation24].

2.3. Statistical analyses

Data analysis was done by statistical indexes (mean, standard deviation, median, minimum, maximum and frequency). First, to evaluate the normality distribution of the quantitative variables (hypogonadism symptoms score, testosterone, FSH and LH, sociodemographic factors) were performed by KolmogorovSmirnova and Shapiro–Wilk tests. Only the scores of the symptoms of hypogonadism and the levels of total testosterone had a normal distribution (p>.05). Therefore, ANOVA and independent t-test were used to evaluate the symptoms of hypogonadism and total testosterone between groups. Non-parametric statistics (Mann–Whitney U-test, Kruskal–Wallis and Spearman correlation coefficients) were used to investigate serum-free testosterone, FSH and LH. In multivariate analysis, logistic regression model with backward LR method was used to identify the predictors of hypogonadism symptoms, Probability for stepwise; entry  = 0.05, removal = 0.1. In this model, the response variable was defined zero (hypogonadism score <34 mean”) and 1 (hypogonadism score≥ 34 “mean”). All tests were two-tailed and p values less than 0.05 were considered significant.

3. Results

The quantitative sociodemographic characteristics of subjects showed in . The assessment of the qualitative variables showed 9.3% illiterate, 41.4% prehigh school, 49.3% diploma and college level, 30% employee, 20% worker and 50% self-employed.

Table 1. Quantitative sociodemographic variables.

According to the AMS scale, 73.6% of men experienced the symptoms of late hypogonadism of whom 33% had low borderline levels of total testosterone and 3.8% had low levels of free testosterone. presents the relationship of late hypogonadism symptoms with sociopersonal factors and testosterone level. The total score of the symptoms of late hypogonadism had a significant relationship with BMI (p = .21) and occupation (p = .005).

Table 2. Comparison the mean of LOH symptoms score according to anthropometric, socioeconomic and biochemical parameters.

The somatic domain of this scale had the highest mean crude score (12.72 ± 5.25). After modification of the three domains scores (sum of the scores of each domain divided by the number of the questions in the domain) by Friedman test was showed a significant difference between the modified scores of the domains (p = .0001); the highest mean score was seen in the psychological domain (mean = 2.23 ± 0.92, median = 2) and the lowest mean score was seen in the somatic domain (mean = 1.82 ± 0.75, median = 1.71). The somatic domain score had a significant association with the occupation (p = .028) and total testosterone levels (p = .03).

Moreover, mental domain score (p = .018) and total score (p  =  0.016) had a significant association with the occupation. There was a borderline significant association between sexual domain score and age (p = .056).

presents the Spearman correlation of hypogonadism symptoms with the levels of sexual hormones and sociodemographic characteristics of men. There was a significant positive correlation between BMI and the hypogonadism symptoms (p = .04, r = .16), BMI and the symptoms in the somatic domain (p = .03, r = 0.17), age and the symptoms in the sexual domain (p = .001, r = 0.24).

Table 3. Spearman's correlation coefficients between quantitative variables.

In this study, four men had low levels of free and total testosterone (normal LH = 2 men, low levels LH  = 2 men). The results of the study showed that the levels of LH and FSH increased with age, and a significant positive correlation was found between the levels of FSH (p = .001, r  =  0.34) and LH (p = .001, r  =  0.25) with age (, ).

Figure 1. Effect of age (years) on LH &FSH levels.

Figure 1. Effect of age (years) on LH &FSH levels.

The final logistic regression model showed that among the study variables (age, occupation, education, income, cigarette smoking, BMI, systolic and diastolic blood pressure, total and free testosterone, FSH and LH), the variables of age (p = .06; borderline significant), occupation p = .038), BMI (p = .008) and smoking status (p = .06; borderline significant) were identified as the predictors of Andropause (hypogonadism Score ≥34 “mean”). In other words, the odds of LOH score ≥34 increased by a factor of 1.05 with every one-year increase in age (odds ratio: 1.05, 95% CI: 1–1.1). The odds of hypogonadism score ≥34 were 4.4 times higher (odds ratio: 4.38, 95% CI: 1.4113.60) in those who were self-employed and 3.1 times higher (odds ratio: 3.14, 95% CI: 1–10.43) in employees in comparison with workers. A 1-unit increase in BMI increased the odds of hypogonadism Score ≥34 by a factor of 1.15 (odds ratio: 1.15, 95% CI: 1.04–1.27) and a one-unit pack-year increase in smoking status increased the odds of the odds of hypogonadism Score ≥34 by a factor of 2.2 (odds ratio: 2.2, 95% CI: 0.94–5.11) ().

Table 4. Logistic regression analyses of LOH symptoms related to anthropometric, socioeconomic and biochemical parameters.

Logit model of hypogonadism symptoms score above mean “34” wasbased on identify predictors in the :  + 0.789 smoking status

4. Discussion

In our study, 73.6% of men over 40 years experienced the symptoms of hypogonadism. Similar results were reported in India in 2011 (71.13%) [Citation25] and in 2014 (82.82%) [Citation26], Korea (75.3%) [Citation19], Iran (73.3%) [Citation18], using the Androgen Deficiency in the Aging Male (ADAM) questionnaire, in Indonesia (70.94%) [Citation23] and Iran in 2012 (51.5%) [Citation27], using the AMS scale. In a study in Iran (2015), the most of men (38.6%) in mild level and (27.1%) in moderate level had experienced the symptoms of hypogonadism severity base on the AMS scale [Citation28].

The results showed men experienced the symptoms of hypogonadism mildly with the mean 33.81 ± 11.36. In this regard, one study reported the mean score of 34.5 ± 11.6 in Japan [Citation15] and another study in Turkey reported the mean score of 30.98 ± 10.93 by using AMS Scale [Citation29].

No significant association was found between experiencing the symptoms of hypogonadism and serum levels of total testosterone, which is in line with the results of other studies although they used the ADAM questionnaire [Citation18,Citation19]. It is contrast with one study which showed the score above 27 (by using AMS scale) that was significantly correlated with total testosterone [Citation17]. The reason for the difference could be the age of men that in the most studies was ≥40 years old while in the last one was ≥50 years old.

We found no significant association between the symptoms of LOH and the serum levels of free testosterone, which is in line with the results of the some studies [Citation17,Citation18]. It seems that factors other than the serum testosterone concentration, like sociodemographic factors including the occupation and BMI may be associated with the experience of hypogonadism symptoms.

This study showed no significant association between the mean of sexual and psychological domains and the serum levels of total and free testosterone, but there was significant association between the mean of somatic domain and total testosterone. However, a study showed a significant association between the score of the psychological domain of hypogonadism symptoms and serum testosterone [Citation15]. Other study indicated an inverse association between some sexual symptoms and levels of total and free testosterone [Citation16]. The reason for the discrepancies could be difference in the culture, lifestyle and physical activity between Iranians, Japanese people and Europeans.

We found no significant association between hypogonadism symptoms and socio-demographic factors such as age, cigarette smoking and blood pressure, while this association was significant between BMI and occupation. This result was in line with a study conducted in Iran [Citation18], but different from the reports in Japan [Citation15]. The reason could be different population. However, another Iranian study reported a significant association between the score of the hypogonadism symptoms and age ≥50 years [Citation27], which is different from our findings. The reason may be different in the sample size or different climatic regions

In this study with an increase in BMI, the score of hypogonadism symptoms increased. This finding was different from results of others [Citation15,Citation18,Citation27]. These inconsistent findings could be the difference in the questionnaire used to evaluate the symptoms of hypogonadism, sample size, and age range of subjects.

Our study showed a significant association between the score of the hypogonadism symptoms and occupation in such a way that the highest scores were observed in self-employed. This finding was similar to the results of other studies that reported this association so that the score was higher in those who were jobless at the time of the study [Citation15,Citation27].

We found no relationship between hypogonadism symptoms score and smoking status while in a study reported a significant association [Citation27]. The reason might be different in the sample size or lifestyle of people between two provinces.

In this study, after modification of domains’ score, the psychological domain had the highest score. It seems that the symptoms of hypogonadism mostly had psychological manifestations. Unlike our finding in a study [Citation15], after modification of the scores, sexual domain had the highest score. The reason for the difference may be that men in this study were all workers, that is, from the same social class while subjects were from different socio-economic classes in terms of (income, occupation and social role) with different psychological needs.

Moreover, FSH and LH levels had a significant positive correlation with age so that the levels increased with age which was in line with the results of a study by [Citation30].

In the final regression model, the association between mean score of hypogonadism symptoms and serum levels of total and free testosterone was not significant. A similar study verified these results [Citation15]. In this model, the score of the hypogonadism symptoms had a significant association with age in such a way that each one-year increase in age, the odds of symptoms increased by 1.05 times. Similarly in another study in Iran, it was 1.03 times [Citation31].

5. Limitations and future research directions

The findings of present study might reflect the experience of hypogonadism symptoms and the association with sexual hormonal indices in our particular study setting of GUMS. Further research is required to investigate the experiences of men who live in other regions. In the context of Iran, most men are not comfortable to talk about their sexual issues. Further researchers could explore the perspectives and experiences of hypogonadism symptoms by using participatory qualitative research design. We could not have a causal interpretation in the cross-sectional design. So, further comparative studies are required to investigate the association between the experience of hypogonadism symptoms and sexual hormonal indices in different age groups by using other research methods.

6. Conclusions

In this study, most men above the age of 40 years experienced the symptoms of hypogonadism and the majority of the symptoms were related to psychological domain. The score of the symptoms in this domain had no association with serum levels of total and free testosterone. Although somatic domain of the symptoms of hypogonadism had the lowest frequency, only the symptoms of this domain had an association with serum level of total testosterone in the study population. Therefore, it could be stated that testosterone deficiency mostly results in the somatic symptoms of hypogonadism.

In addition, the symptoms of hypogonadism were associated with some factors such as BMI and occupation. It seems that a healthy lifestyle and weight control might be effective role in controlling the symptoms of hypogonadism. Since hypogonadism symptoms had a significant association with occupation, a survey to determine occupational needs in future using the related standard questionnaires deeply was suggested.

Ethical approval

This article has been taken from the nursing master's thesis in the form of approved projects by Ethical Committee at the University of Medical Sciences, Rasht, with the number ((Ref. IR, GUMS.REC.1394.31) on May, 2015.

Acknowledgements

The researchers would like to thank the Social Determinants of Health Research Center (SDHRC), research deputy and Health Department of Guilan University of Medical Sciences and everyone who participated in this project and helped using conducting this study.

Disclosure statement

All of the authors have no conflict of interest to declare with regard to this paper.

Additional information

Funding

The study was supported by Guilan University of Medical Sciences and Social Determinants of Health Research Center (SDHRC).

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