The goal was to clarify the rate of major depressive disorder (MDD) in self-referred patients who visited our late onset hypogonadism (LOH) clinic and the importance of screening of MDD in LOH clinic. Two hundred consecutive self-referred patients who visited our LOH clinic were evaluated. MDD was diagnosed using, the Mini International Neuropsychiatric Interview (MINI) questionnaire. Scores of the Aging Males Symptom (AMS) scale were compared between the MDD and non-MDD groups with and without low testosterone values. Forty-two percent of all patients were categorized into the MDD group. Only 4% of the patients were considered to be LOH. The MDD group had significantly higher scores on the AMS scale than the LOH and non-MDD with normal testosterone groups. In conclusion, significant numbers of undiagnosed MDD patients visited the LOH clinic. Screening for MDD is an essential step in the LOH outpatient clinic.
Late onset hypogonadism (LOH) is a clinical and biochemical syndrome associated with advancing age and characterized by typical symptoms and a deficiency in the serum testosterone level.1, 2 This syndrome is an important concept in maintaining and improving the physical and mental conditions of aging men. However, this hypothesis is not fully supported by solid evidence.3, 4 The clinical entity of LOH and its diagnosis are still controversial.2, 4, 5 Validated questionnaires6, 7 and biochemical assays, which are technically reliable and reproducible, do not appear to be precise enough diagnostically.4, 8, 9, 10 The lack of accurate methods for diagnosis of LOH suggests the importance of differential diagnosis in the clinical setting. In particular, major depressive disorder (MDD) should be considered as the first differential diagnostic disease because of overlapping of the symptoms of LOH and MDD. Previous pilot studies have suggested that a significant number of MDD patients visit LOH clinics.11, 12
In this regard, the goal of this study was to clarify the rate of MDD in self-referred patients who visited our LOH outpatient clinic and the importance of screening for MDD in the LOH clinical setting.
Patients and methods
In this study, we analyzed 200 consecutive self-referred patients with suspected LOH in our LOH outpatient clinic from October 2004 to December 2005. The hospital review board approved this study. The age distribution of the patients by decade was 18 (9%) in their 30s, 61 (31%) in their 40s, 72 (36%) in their 50s, 31 (15%) in their 60s and 18 (9%) aged 70 years or older. Patients in their 30s, 40s and early 50s who seemed to be young for the definition of LOH were included in this study to clarify the actual entity of self-referred patients with suspected LOH. The chief complaints of all patients are described in Table 1. The main symptom was a depressive mood. Forty-five patients (22.5%) were diagnosed as having depressive disorder before visiting our clinic by psychiatrists. They were categorized as the MDD group (Figure 1).
History taking, questionnaires and endocrinological evaluation were employed for diagnosis. The questionnaires used were the Mini International Neuropsychiatric Interview (MINI)13 and the Aging Males Symptom (AMS) scale.6 The MINI is employed for diagnosis of MDD. The following nine symptoms are assessed in the module: (1) depressive mood for at least 2 weeks; (2) loss of interest or pleasure in nearly all activities for at least 2 weeks; (3) changes in appetite or weight. (4) sleep disturbance; (5) changes in psychomotor activity; (6) decreased energy; (7) feelings of worthlessness or guilt; (8) difficulty in thinking, concentrating or making decisions and (9) recurrent thoughts of death or suicidal ideations, plans or attempts. A patient can be diagnosed with MDD when he answers positively to symptoms (1) and/or (2), and gives positive answers for at least five of the nine symptoms. A linguistically validated Japanese version of the AMS scale was employed.14 The AMS scale consists of 17 questions that categorize three subscales (psychological, somatic and sexual). Each item has a response with five degrees of severity (1–5 points: none=1, mild=2, moderate=3, severe=4 and extremely severe=5). The severity of symptoms according to the total score was categorized as none/little (17–26), mild (17–36), moderate (37–49), and severe (50 or more).
The most widely accepted and reliable testosterone assay is to calculate free testosterone level from total testosterone and sex hormone-binding globulin (SHBG).1, 15 However, clinical usage of SHBG is quite difficult in our country because of our insurance system.16 Thus, in this study, we used serum total testosterone (total T) measured by the radioimmunoassay (RIA) as a parameter for hypogonadism.17 There are no generally accepted lower limits for the normal testosterone (normal T) level and it is unclear whether geographically different thresholds depend on ethnic differences.1 Thus the reference range for total T of Japanese male adults was applied as a criterion for a low total testosterone level.18 The reference range of total T was 2.01–7.50 ng/ml. Our LOH outpatient clinic started at 1300. Thus blood sampling was done in the afternoon (1300–1500) for all except for 18 cases. In this study, we could not re-evaluate the abnormal total T value in the morning.
Comparison of the AMS scores and correlations between the AMS scale and total T values
According to previsit diagnosis of depressive disorder, the results of the MINI questionnaire and the total T value, the patients were categorized into the following four groups: MDD with normal total T, MDD with low testosterone (low T), non-MDD with normal T and non-MDD with low T (LOH). Total and subscale (psychological, somatovegetative and sexual) scores of the AMS scale were compared among these four groups. The correlations of those scores and total T levels were calculated for all cases and each categorized group. In the current study, we did not use categorized severities according to total and subscale scores.
For comparative analysis of the AMS scores of the categorized groups, we used ANOVA and Fisher's protected least significant difference (PLSD) test. Correlations between the AMS scores and serum total T levels were analyzed using Pearson's correlation coefficient. Statistical significance was defined as P<0.05.
Rate of major depression and LOH
Totally, 84/200 of the patients (42%) were categorized into the MDD group. Forty-five out of 200 cases (22.5%) of MDD were diagnosed by psychiatrists before the patients visited our hospital. Thirty-nine patients out of 200 cases (19.5%) were newly diagnosed with MDD by the MINI questionnaire (Figure 1). Among the MDD patients, 79/84 patients of the MDD group (94.0%) and 5/84 of the patients (6.0%) showed normal (MDD with normal T group) and low testosterone (MDD with low T group) levels, respectively. On the other hand, 116/200 of the patients (58%) were categorized into the non MDD group. Eight out of 116 of non-MDD patients (6.9%) had low total testosterone levels. They were defined as the LOH (non-MDD with low T) group. One hundred eight out of 116 of non-MDD patients (93.1%) had normal total T levels (non-MDD with normal T).
Comparison of the AMS scores of the four categorized groups
In the comparison of total scores of the AMS scale, there was no significant difference between non-MDD groups (Table 2). The MDD groups had significantly higher total scores than the non-MDD groups. In the comparison of the subscale scores, those in the MDD groups had significantly higher psychological and somatovegetative subscale scores than the non-MDD groups. The sexual subscale score of the MDD with normal T group was significantly higher than that of the non-MDD with normal T group.
Correlations between the AMS score and total testosterone levels
There was no significant correlation between the total and subscale scores of the AMS scale and total testosterone levels in the MDD and non-MDD groups.
The first significant finding of the current study was that a predominant population of the patients who visited our LOH clinic suffered from MDD, not LOH. Surprisingly, MDD and LOH patients comprised 42% and only 4% of all self-referred patients, respectively, although the prevalence of LOH depends on the definition of ‘hypogonadism’1 and age distribution of the patients. These results clearly indicated the importance of differential diagnosis of MDD in the LOH clinic.
In this study, we did not use the calculated free T as a testosterone assay.1 In addition, blood sampling was done in the afternoon. Thus our study had these limitations on hormonal evaluation. However, the American Association of Clinical Endocrinologists (AAEC) medical guidelines recommend that men with a normal total T level do not need further examination.17 Most of our patients show normal total T level. Some patients with lower total T values from afternoon samples might have normal T values in morning samples.
These results suggest that most patients in our LOH clinic may not have significant hypogonadism. In addition, we could not find out any significant correlations between the AMS scores and serum total testosterone levels in MDD or non-MDD patients. Some previous studies demonstrated that the total AMS score and its subscale scores were not related to the levels of serum testosterone or other hormones9, 10 such as growth hormone and DHEA-S.8 The current and these previous studies suggested that patients' symptoms (scores) were not associated with testosterone level in LOH clinic.
The severe depressive symptoms of the MDD patients resulted in significantly higher scores of the AMS scale than those of the non-MDD patients with low T (LOH) and normal T levels. Yoshida et al.11 also reported that the AMS scale did not differentiate between patients with or without MDD. Although the AMS scale, which was designed as a health-related quality-of-life scale, is used for diagnosis of LOH worldwide, the AMS scale could not provide a differential diagnosis between LOH and MDD.
One of the reasons for predominance of MDD is the resemblance between symptoms of MDD and LOH. According to the International Society of Andrology (ISA), International Society for the Study of the Aging Male (ISSAM) and European Association of Urology (EAU) recommendations,1, 2 the characterized symptoms of LOH include decreased sexual desire and changes in mood and sleep disturbance. Those symptoms are also typical ones in MDD. In addition, the news medias of our country tend to insist on the psychological aspects of LOH, but not physiological effects on muscle, fat, bone and the cardiovascular system. As a consequence, significant numbers of undiagnosed MDD patients visited our clinic. Some diagnosed MDD patients also want to check up LOH. This prevalence of MDD is higher than that in the primary care setting.19 Therefore differential diagnosis for MDD should be done first. Undiagnosed MDD patients should receive proper treatment as ‘MDD’, because the importance of initial treatment in MDD is established. Doctors who see LOH patients must have basic knowledge of the management of MDD and should have a screening tool for it. Cooperation with psychiatrists is also essential in the LOH clinic and we refer moderate and severe MDD patients to psychiatrists.
In conclusion, the predominant population of self-referred patients in our LOH outpatient clinic was MDD. The AMS scale cannot differentiate between MDD and LOH. Screening for MDD is an essential step in the LOH outpatient clinic.
Nieschlag E, Swerdloff R, Behre HM, Gooren LJ, Kaufman JM, Legros JJ et al. Investigation, treatment and monitoring of late-onset hypogonadism in males. Aging Male 2005; 8: 56–58.
Lunenfeld B, Saad F, Hoesl CE . ISA, ISSAM and EAU recommendations for the investigation, treatment and monitoring of late-onset hypogonadism in males: scientific background and rationale. Aging Male 2005; 8: 59–74.
Morales A . Andropause (or symptomatic late-onset hypogonadism): facts, fiction and controversies. Aging Male 2004; 7: 297–303.
Black AM, Day AG, Morales A . The reliability of clinical and biochemical assessment in symptomatic late-onset hypogonadism: can a case be made for a 3-month therapeutic trial? BJU Int 2004; 94: 1066–1070.
T'Sjoen G, Feyen E, De Kuyper P, Comhaire F, Kaufman JM . Self-referred patients in an aging male clinic: much more than androgen deficiency alone. Aging Male 2003; 6: 157–165.
Heineman LAJ, Zimmermann T, Vermeulen A, Thiel CA . New ‘Aging male symptoms’(AMS) rating scale. Aging Male 1999; 2: 105–114.
Morley JE, Charlton E, Patrick P, Kaiser FE, Cadeau P, McCready D et al. Validation of a screening questionnaire for androgen deficiency in aging males. Metabolism 2000; 49: 1239–1242.
Miwa Y, Kaneda T, Yokoyama O . Correlation between the Aging Males Symptoms Scale and sex steroids, gonadotropins, dehydroepiandrosterone sulfate, and growth hormone levels in ambulatory men. J Sex Med 2006; 3: 723–726.
Tsujimura A, Matsumiya A, Miyagawa Y, Takao T, Fujita K, Takada S et al. Comparative study on evaluation methods for serum testosterone level for PADAM diagnosis. Int J Impot Res 2005; 17: 259–263.
G T'Sjoen S, Goemaere M, De Meyere J, Kaufman M . Perception of males aging symptoms, health and well being in elderly community-dwelling men is not related to circulating androgen level. Psychoneuroendocrinology 2004; 29: 201–214.
Yoshida N, Kumano H, Kuboki T . Does the aging males symptoms scale assess major depressive disorder: a pilot study. Maturitus 2005; 53: 171–175.
Sato Y, Kato S, Ohnishi S, Nakajima H, Nanbu A, Nitta T et al. Analysis of clinical manifestations and endocrinological aspects of patients having PADAM-like symptoms. Nippon Hinyokika Gakkai Zasshi 2004; 95: 8–16.
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59: 22–33.
Heinemann LAJ, Saad F, Zimmerman T, Annoesjka N, Myon E, Xavier B et al. The Aging Males Symptoms (AMS) scale: update and complication of international versions. Health Qual Life Outcomes 2003; 1: 15–20.
Vermeulen A, Verdonck L, Kaufman JM . A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endcrinol Metab 1999; 84: 3666–3672.
Sato Y, Tanda H, Kato S, Ohnishi S, Nakajima H, Nanbu A et al. Serum testosterone level using the radioimmunoassay method in healthy Japanese male volunteers. Reprod Med Biol 2006; 5: 37–41.
Bhasin S, Cunningham GR, Hayes FJ, Matsumoto AM, Snyder PJ, Swerdloff RS et al. Testosterone therapy in adult men with androgen deficiency syndromes: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2006; 91: 1995–2010.
Iwamoto T, Yanase T, Koh E, Horie H, Baba K, Namiki M et al. Reference ranges of total serum and free testosterone in Japanese male adults. Nippon Hinyokika Gakkai Zasshi 2004; 95: 751–760.
Ansseau M, Dierick M . High prevalence of mental disorder in primary care. J Affect Disord 2004; 78: 49–55.
About this article
Cite this article
Sato, Y., Tanda, H., Kato, S. et al. Prevalence of major depressive disorder in self-referred patients in a late onset hypogonadism clinic. Int J Impot Res 19, 407–410 (2007). https://doi.org/10.1038/sj.ijir.3901551
- late onset hypogonadism
- major depressive disorder
- AMS scale
Aging Clinical and Experimental Research (2015)
Reproductive Medicine and Biology (2012)
The aging males’ symptoms scale for Japanese men: reliability and applicability of the Japanese version
International Journal of Impotence Research (2008)