This study summarizes the literature on the prevalence, incidence, and proportion of patients receiving treatment for male hypogonadism and a systematic literature search was performed for articles published in the last 20 years. Of the 97 studies identified, 96 examined the prevalence, 2 examined the incidence, and 4 examined the proportion of males with hypogonadism patients receiving treatment. Based on studies conducted in Europe and USA, the prevalence of hypogonadism in the general population ranged from 2.1% to 12.8% of middle-aged to older men, with an estimated incidence of 12 new cases per 1,000 person-years. Prevalence was higher among patients with comorbid conditions, such as type 2 diabetes mellitus and obesity. Approximately 10–12% of men with hypogonadism were receiving testosterone treatment. This literature review suggests that there is potentially a significant burden of hypogonadism in the general population. Burden seems to increase with age and in the presence of certain disease conditions. Data suggests that many hypogonadal men who may benefit from testosterone replacement are not receiving treatment. This may be the result of underdiagnosis of the disease, lack of awareness by patients or physicians, irregularities surrounding the diagnostic criteria, and deficiency of long-term safety studies.

1. Introduction

Hypogonadism in men has been defined as a clinical syndrome resulting from failure of the testis to produce physiological levels of testosterone (androgen deficiency) and a normal number of spermatozoa, due to disruption of one or more levels of the hypothalamic-pituitary-testicular axis [1]. A diagnosis of hypogonadism is typically based on the signs and symptoms associated with low T, followed by biochemical confirmation of low testosterone (T) [1]. The most widely accepted parameter used to establish hypogonadism is the measurement of serum total testosterone (TT) [1]; however, cut-off values used to indicate hypogonadism have not been clearly defined and vary across studies. Recent clinical practice guidelines published by the Endocrine Society have reported that the average TT threshold, at which the likelihood of most symptoms associated with hypogonadism increases, corresponds to the lower limit of the normal range for young men, that is, approximately 300 ng/dL (10.4 nmol/liter) [1]. Correspondingly, a common threshold used in the literature to indicate hypogonadism is serum TT <300 ng/dL (<10.4 nmol/L); however, cut-off values of <200 ng/dL (6.94 nmol/L) to <350 ng/dL (<12 nmol/L) are not uncommon. These thresholds are sometimes combined with requisite signs and symptoms, but not always. The result is a range of operational definitions of hypogonadism used in the literature, varying in degree of stringency and potentially leading to variations in estimates of prevalence of the disease.

The literature on the epidemiology of hypogonadism is confounded by considerable heterogeneity across studies, varying not only by operational definition but also by patient populations, study design, time frame of study, and geography. Estimates of prevalence, incidence, and treatment rates are influenced by all of these factors. The aim of this systematic review of the epidemiology of hypogonadism was to determine the prevalence and incidence of hypogonadism, as well as the proportion of males with hypogonadism receiving treatment of hypogonadism, while accounting for differences in patient and study characteristics and operational definition of hypogonadism used.

2. Methods

2.1. Eligibility Criteria

Eligible studies were defined in this systematic review as original studies that assessed the prevalence, incidence, or treatment rates of adult males (≥18 years of age) with hypogonadism, acquired or idiopathic. Studies on genetic forms of hypogonadism (i.e., Klinefelter’s syndrome) and secondary publications of the same results were not included. Observational studies with sample sizes >30 were included in this review; treatment and intervention studies were excluded.

2.2. Search Methods for Identification of Studies

Three pharmacologic and biomedical literature databases were searched for this systematic literature review: PubMed/MEDLINE database, Cochrane Library Database, and EMBASE. Search strings composed of medical subject heading (MeSH) terms, from the controlled vocabulary indexing hierarchy and/or in-text terms in title and/or abstract fields, were used (Table 1). Citations were limited to English language articles, published during a 20-year period (January 01, 1992, to August 31, 2012). The reference list of included publications was searched for relevant articles.

Table 1. Search strategy executed in PubMed/MEDLINE, EMBASE, and The Cochrane Central Register of Controlled Trials August 31, 2012, and incidence, prevalence, and treatment rates.

Search	Search string [field]	Hits
1	Search “hypogonadism/epidemiology” [mesh]	345
2	Search hypogonadism [title] OR testosterone deficiency* [title] OR “testosterone/deficiency” [mesh] OR testoid deficiency* [title] OR androgen deficiency* [title] OR testosterone replacement therapy* [title]	3173
3	Search epidemiology* [title/abstract] OR incidence [title/abstract] OR prevalence [title/abstract] OR rate [title/abstract] OR rates [title/abstract] OR treatment rate [title/abstract] OR treatment rates [title/abstract]	2380843
4	Search (“epidemiology” [mesh]) OR “incidence” [mesh] OR “prevalence” [mesh])	318545
5	Search #3 OR #4	2472821
6	Search #2 AND #5	331
7	Search #1 OR #6	603
8	Search #7 filters: publication date from 1992/01/01 to 2012/8/31; humans; English; male; adult: 19+ years	298
8	Non-English articles	21

2.3. Data Extraction

We abstracted key data elements using a standardized abstraction tool, including type of research design, country, study period, sample size, operational definition of hypogonadism used, study population characteristics, and outcomes. One author screened the search results against the predefined inclusion and exclusion criteria. Titles were evaluated, abstracts were reviewed, and potentially relevant full-text articles were evaluated for relevance. A quality check was conducted on 20% of the abstracts by a second reviewer.

We categorized studies based on population of interest: population-based studies were those with large sample sizes (>1 thousand) and minimal age restrictions and conducted in a specific geographical location; community-based studies were those with relatively smaller sample sizes (i.e., hundreds) and more restricted age ranges and conducted in a specific geographical location; primary care-based studies were those that recruited patients from a general primary care or medical clinic seeking medical care; screening-based studies recruited healthy individuals from a general health screening clinic. Primary care-based studies and screening-based studies were classified together as they were conducted in the same setting. Finally, clinical condition-based studies were those that examined prevalence of hypogonadism in patient populations with specific clinical conditions. We also separately summarized prevalence of hypogonadism by age for studies that provided these data.

3. Results

3.1. Literature Search Results

The literature search identified 1,395 articles that were reviewed for inclusion. After review of titles and abstracts, we evaluated 175 full-text articles and identified 97 articles that met our eligibility criteria: 96 reported on the prevalence of hypogonadism, 2 on the incidence, and 4 on treatment proportions (not mutually exclusive). The PRISMA (preferred reporting items for systematic reviews and meta-analyses) flow chart can be found in Figure 1.

Details are in the caption following the image — **Figure 1**
Open in figure viewer PowerPoint

Flow diagram.

3.2. Prevalence of Hypogonadism

Among the 96 identified prevalence studies, 7 were population- (n = 4) [2–5] or community- (n = 3) [6–8] based studies and 7 were primary care or health screening studies [9–15]. Ten examined age-related changes for hypogonadism [2, 3, 8, 9, 12, 13, 16–19] and seventy-eight were clinical condition-based studies [20–97]. Studies varied considerably in geographic location, patient characteristics, sample sizes, and operational definition for hypogonadism. These studies are described in Tables 2 and 3.

Table 2. Prevalence of hypogonadism in population-, community-, and primary care or screening-based populations.

Author, year, and study name	Country and years of data collected	Study design	N	Age, mean (SD), and range	Definition of hypogonadism used	Reported prevalence (%)
Population-based studies
Haring et al., 2010 [5] (SHIP)	Germany, 1997–2001	Population-based	1490	50.65 (15.41), NR	TT < 300 ng/dL	12.8
Araujo et al., 2007 [3] (BACH)	USA, 2002–2005	Population-based	1475	47.3 (12.5), NR	TT < 300 ng/dL + FT < 5 ng/dL + ≥1 specific symptom or ≥ 2 nonspecific symptoms^†	5.6
Araujo et al., 2004 [2] (MMAS)	USA, 1987–1997	Population-based	1691	NR (NR), 40–70**	TT < 200 ng/dL + ≥3 symptoms^††; OR: TT 200–400 ng/dL + FT< 8.91 ng/dL + ≥ 3 symptoms^††	6
Tajar et al., 2012 [4] (EMAS)	8 European countries, 2003–2005	Population-based^†††	2966	59.15 (10.82), 40–79	TT < 317 ng/dL + 3 specific symptoms*	2.1

Community-based studies
Ponholzer et al., 2010 [6]	Austria, 2000–2002	Community-based	247	75.8 (0.4), 75–78	TT < 350 ng/dL	31.2
Khoo et al., 2008 [7]	Malaysia, NR	Community-based	351	58 (7), 50–93	TT < 317 ng/dL	19.1
					TT < 317 ng/dL + positive symptoms on ADAM	6
Wong et al., 2006 [8]	China (Hong Kong), 2003-2004	Community-based	252	54 (NR), 45–64	TT < 200 ng/dL + ≥3 of 7 symptoms OR: TT 200–400 ng/dL + FT < 0.3093 nmoL/L + ≥3 of 7 symptoms	9.52

Primary care and screening studies
Mulligan et al., 2006 [13] (HIM)	USA, 2003-2004	Primary care patients	2162	60.5 (10.33), 45–96	TT < 300 ng/dL	38.7
Schneider et al., 2009 (DETECT) [15]	Germany, 2003	Primary care patients	2719	58.7 (13.4), NR	TT < 300 ng/dL	19.3
Nardozza et al., 2011 [14]	Brazil, 2009	Health screening	1623	57 (NR), 24–87	TT < 300 ng/dL	19.8
Goel et al., 2009 [11]	India, 2006	Health Screening^††††	157	53.1 (NR), 40–60;	TT < 300 ng/dL	24.2
					TT < 300 ng/dL + Symptoms	20.4
Liu et al., 2009 [12]	Taiwan, 2007-2008	Health screening	734	57.4 (6.7), 43–87	TT < 300 ng/dL	24.1
					TT < 300 ng/dL + FT < 5 ng/dL + symptoms	12
Blümel et al., 2009 [9]	Chile, NR	Primary care patients	96	55.1 (12.0), 40–85	BT <198.4 ng/dL + symptoms***	28.1
Di Luigi et al., 2010 [10]	Italy	Health screening	183	61.9 (7.5), 50–75	TT < 230 ng/dL	12

TT: 200 ng/dL = 6.94 nmol/L; 230 ng/dL = 8 nmol/L; 300 ng/dL = 10.4 nmol/L; 317 ng/dL = 11 nmol/L; 350 ng/dL = 12 nmol/L; FT: 5 ng/dL = 0.17 nmol/L; 8.9 ng/dL = 0.3092 nmoL/L.
ADAM: androgen deficiency in the aging male; BACH: Boston Area Community Health; BT: bioavailable testosterone; cFT: calculated free testosterone; DETECT: diabetes cardiovascular risk-evaluation: targets and essential data for commitment of treatment; EMAS: European Male Aging Study; HIM: hypogonadism in males; MMAS: Massachusetts Male Aging Study; NR = not reported; SHIP = Study of Health in Pomerania; TT = total testosterone.
*Decreased frequency of morning erections, sexual thoughts, and erectile dysfunction.
**Participants were equally divided between men in their 40s, 50s, and 60s with a similar mean age to the BACH data.
***Positive answer to items 1 or 7, or any 3 other questions on the ADAM questionnaire.
^†Specific symptoms include low libido, erective dysfunction, or osteoporosis; the nonspecific symptoms include sleep disturbance, depressed mood, lethargy, or low physical performance.
^††Symptoms include loss of libido, erectile dysfunction, depression, lethargy, inability to concentrate, sleep disturbance, irritability, and depressed mood.
^†††4.4% of original population were excluded which included men already receiving testosterone replacement therapy.
^††††Study subjects were healthy hospital employees volunteered for a health check-up.

Table 3. Prevalence of hypogonadism among patients with specific conditions.

Author, year, and study name	Country and years of data collected	Study population	N	Definition of hypogonadism used	Prevalence (%) among patients with disease of interest
Type 2 diabetes mellitus (T2DM)
Kapoor et al., 2007 [56]	UK/not specified	Primary care retinopathy Screening service and medical clinic	355 men with T2DM	TT < 8 nmol/L TT 8–12 nmol/L	17 25
Biswas et al., 2012 [25]	UK/not specified	Medical clinic	329 T2DM (n = 115) T1DM (n = 93) controls (n = 12)	TT < 11.9 nM	45
Chen et al., 2006 [29]	Australia/NZ/1992 to 2000	Population-based	195 T2DM (n = 35) Non-T2DM (n = 160)	TT < 8.0 nmol/L	14.3
Corona et al., 2006 [36]	Italy/not specified	Medical clinic	1246 T2DM (n = 199)	TT < 10.4 nmol/L	24.5
Anderson et al., 2012 [23]	UK/January 2008–June 2009	Medical clinic	387 T2DM (n = 353) T1DM (n = 23)	TT < 8.0 nmol/L TT 8–11.99 nmol/L	4.4 32.1
Talukder et al., 2010 [87]	India/May 2008–April 2009	Medical clinic	420 T2DM (n = 170) non-T2DM (n = 40)	Symptoms/signs of hypogonadism and TT ≤ 12 nmol/L	34.7
Dhindsa et al., 2004 [40]	US/not specified	Medical clinic	103 men with T2DM	TT < 300 ng/dL	33
Grossmann et al., 2008 [48]	Australia/not specified	Medical clinic	649 T2DM (n = 574) T1DM (n = 69)	TT < 10 nmol/L	43
Grossmann et al., 2009 [47]	Australia/2005	Medical clinic	464 men with T2DM	TT < 10 nmol/L	43
La Vignera et al., 2009 [61]	Italy/not specified	Medical clinic	110 men with T2DM	TT < 231 ng/mL	10
Ogbera et al., 2011 [71]	Nigeria/December 2009 to May 2010	Medical clinic	203 men with T2DM	TT < 8 nmol/L	36
Hackett et al., 2009 [50]	UK/September 2007 and May 2008	Medical clinic	488 men with T2DM	TT < 8 nmol/LTT 8–12 nmol/L	15.5 33.8
Ganesh et al., 2009 [45]	India/not specified	Medical clinic	100 men with T2DM	cFT < 64.8 pg/mL (0.225 nmol/L)	15

T2DM + obesity or metabolic syndrome (MetS)
Ogbera 2011 [70]	Nigeria/December 2009 to May 2010	Medical clinic	203 men with T2DM + MetS (n = 90)	T2DM + TT < 12 nmol/L	36
				T2DM + MetS	43
				T2DM + MetS + low TT	47
Dhindsa et al., 2010 [39]	US/not specified	Medical clinic	1849	FT < 300 ng/dL or 10.4 nmol/L:
			Obesity + T2DM (n = 398)	Obesity and T2DM	51
			Obesity (n = 398)	Obese	31

Obesity
Hofstra et al., 2008 [54]	The Netherlands/not specified	Medical clinic	160 obese males	TT < 11 nmol/L	57.7
Pellitero et al., 2012 [74]	Spain/not specified	Clinical research center	33 obese males	TT < 300 ng/dL	78.8
				TT < 200 ng/dL + FT <65 pg/mL	100
				TT < 300 but >200 ng/dL	23.1
				FT low and TT > 300 ng/dL	3.85
Allan et al., 2006 [22]	Australia/May 2001–February 2003	Community-based	223	TT < 8 nmol/L plus symptoms
			Obese (n = 99)	Obese	15
			Nonobese (n = 124)	Nonobese	3

MetS
Laaksonen et al., 2005 [62]	Finland/1987–2001	Population-based	854 men with MetS	TT < 11 nmol/L	10.7
Singh et al., 2011 [83]	India/not specified	Medical clinic	95 men with MetS	FT < 0.225 nmol/L	30.2
Caldas et al., 2009 [27]	Brazil/January 2003 to March 2007	Medical clinic	80 men with MetS	TT < 300 ng/dL	30.0

Cardiac disease
Jankowska et al., 2006 [55]	Poland/October 2001 to November 2002	Medical clinic	574 CHF (n = 208) health controls (n = 366)	Serum TT and FT levels at or below the 10th percentile of healthy peers	13–39 (by age)
Wang et al., 2010 [94]	China/March 1, 2005, to May 31, 2007	Medical clinic	175 men with CHF	Serum levels at or below the 10th percentile of healthy peers	21.7
Serra et al., 2012 [84]	Italy/not specified	Medical clinic	52 male heart transplantation recipients	TT < 10.4 nmol/L	34.6
Florvaag et al., 2012 [44]	Germany/not specified	Medical clinic	137 male heart failure patients	Free testosterone (age-related cut-off values)	39
Malkin et al., 2010 [67]	UK/June 2000 and June 2002	Medical clinic	930 men with coronary disease	TT < 8.1 nmol/L	16.9
Wehr et al., 2010 [95]	Germany/1997 to 2000	Medical clinic	2299 men who were routinely referred for coronary angiography	T < 11.3 nmol/L	18
Lerchbaum et al., 2012 [65]	Germany/1997–2000	Medical clinic	2069 men with coronary disease	TT < 11.3 nM	18.4

Erectile dysfunction (ED)
Köhler et al., 2008 [59]	US/1987 to 2002	Chart review	2794 men presenting for ED evaluation	TT < 300 ng/dL	23
Bunch et al., 2002 [26]	US/1996 to 1999	Chart review	501 men with ED	TT < 300 ng/dL	44
Corona et al., 2009 [33]	Italy/not specified	Chart review	2302 men with ED	TT < 12 nmol/L + symptoms	28.1
Arafa et al., 2012 [24]	Egypt/not specified	Medical clinic	212 men T2DM + ED	TT < 300 ng/dL + symptoms	41
Guay et al., 2010 [49]	US/July 1995 to July 1997	Chart review	990 with men ED	10.4 nmol/L + symptoms	36.3
Makhlouf et al., 2008 [66]	US/July 2001 to June 2003	Medical clinic	157 men with ED	TT < 300 mg/dL	36
Corona et al., 2007 [35]	Italy/not specified	Medical clinic	1134 men with ED	TT < 10.4 nmol/L	16.9
Corona et al., 2010 [37]	Italy/2000 to 2007	Medical clinic	1687 men with ED	TT 230–300 ng/dL no symptoms	13.3
Corona et al., 2009 [34]	Italy/January 2001 to April 2008	Medical clinic	1093 men with ED
Somani et al., 2010 [85]	UK/March 2007–August 2008	Medical clinic	124 men with ED	Low TT (not further defined)	23.4
Corona et al., 2010 [32]	Italy/January 2001–April 2009	Medical chart review	3712 men with sexual dysfunction	TT <8 nmol/L + symptoms	7.5
Tan et al., 2011 [88]	Multiethnic Asia/Pacific/2003	Medical chart review	1046 ED (n = 194)	TT < 10.4 nmol/L	20.4
Hamidi et al., 2012 [52]	Iran/November 2009 to August 2010	Medical clinic	241 men with ED	FT < 5 ng/dL	36.5

HIV
Klein et al., 2005 [58]	US/not specified	Community-based	502 (had or at risk of HIV)	TT < 300 ng/dL	45.6
Crum-Cianflone et al., 2007 [38]	US/September 2004 to May 2005	HIV medical clinic	300 HIV+	TT < 300 ng/dL	17
Wahlstrom et al., 2000 [93]	US/not specified	Observational study	20 HIV+	T ≤ 410 ng/dL	25
Collazos et al., 2009 [31]	Spain/not specified	Medical chart review	188 HIV+	T < 2.6 ng/mL	3.7
Wunder et al., 2007 [96]	Switzerland/not specified	Cohort study	139 HIV+	FT below the age-adjusted normal limits	70
Wagner et al., 1995 [92]	US/not specified	Study setting (baseline data)	234 HIV+	TT ≤ 400 ng/dL	38
Rietschel et al., 2000 [78]	US/November 1997–April 1999	Cohort study	90 HIV+	Low TT/FT	19

Respiratory disease
Laghi et al., 2005 [64]	US/not specified	Cohort study	101 men with COPD	FT < 50 pg/mL	37.6
Kirbas et al., 2007 [57]	Turkey/November 2004 to July 2006	Medical clinic	96 men with obstructive sleep apnea	TT < 2.62 ng/mL	19.8
Halabi et al., 2011 [51]	US/not specified	Medical clinic	104 men with COPD	FT < 35 pg/mL for patients <70 years; FT < 30 pg/mL for patients ≥70 years	33.6

Depression
Hintikka et al., 2009 [53]	Finland/1998, 1999, 2001, and 2005	Population-based	116 with and without psychological symptoms	FT < 160 pmol/L plus BDI scores:
				+depressive symptoms	28.8
				−depressive symptoms	10.5
McIntyre et al., 2006 [68]	Canada/not specified	Medical clinic	94 men with and without depression	TT < 12.14 nmol/L:
				Men with depression	34
				Men without depression	6

Cancer
Tromp et al., 2011 [91]	The Netherlands/2008	Medical clinics	565 male 5-year survivors of childhood cancer	T < 11.0 nmol/L	12.4
Lackner et al., 2007 [63]	Austria/not specified	Medical clinic	68 men with testicular cancer	T < 3.0 ng/mL + symptoms	33.8
Pühse et al., 2011 [75]	Germany/2004	Medical clinic	376 men with testicular germ-cell cancer (TGCC)	TT 2.84 ng/mL or 9.85 nmol/L	~25
Fleishman et al., 2010 [43]	US/July 2007 through July 2009	Medical clinic	428 male patients with nontestosterone-related cancer	TT < 300 ng/dL	48
Salonia et al., 2011 [80]	Italy/June 2006 and June 2008	Medical clinic	673 prostate cancer patients	TT < 3 ng/mL	21.4%
Greenfield et al., 2007 [46]	US/not specified	Medical clinic	389 cancer survivors	TT < 10 nmol/L	13.6
Rajagopal et al., 2004 [76]	US/not specified	Chart review	40 cancer survivors	<345 ng/dL
				All	65
				On opioids	90
				Not on opioids	40
Schatzl et al., 2001 [82]	Austria/January 1999–April 2000	Medical clinic	156 men with prostate cancer	TT <3.0 ng/mL	33.3
Romerius et al., 2009 [79]	Sweden/2004–2006	Medical clinic	292 men with history of childhood treatment of cancer or brain tumor	T < 10 nmol/L	23

Rheumatoid arthritis (RA)
Tengstrand et al., 2002 [89]	Sweden/not specified	Medical clinic	104 patients with RA	<6.5 nmol/L–8.1 nmol/L (age dependent)	31.7

Osteoporosis
Fink et al., 2006 [42]	US/March 2000 to April 2002	Medical clinics	3674 men with osteoporosis	TT < 200 ng/dL	6.9
Clapauch et al., 2008 [30]	Brazil/January 2005	Medical clinic	216 men with osteoporosis	cFT < 6.5 ng/dL + symptoms	25

Chronic kidney disease (CKD)
Yilmaz et al., 2011 [97]	Turkey/March 2006 to June 2010	Medical clinic	239 men with CKD	TT 10 nmol/L	33
Carrero et al., 2011 [28]	Sweden/June 1999 and October 2007	Medical clinics	260 men with ESRD	TT < 10 nmol/L	44
Kyriazis et al., 2011 [60]	Greece/October 2005 and December 2006	Medical clinic	111 male hemodialysis patients	TT < 8 nmol/L	49
Albaaj et al., 2006 [21]	UK/not specified	Medical clinic	214 male patients with CKD or ESRD	TT < 10 nmol/L	26.2

Myopathies
Travison et al., 2008 [90]	Canada/3-year study	Medical clinic	59 men with myopathies	10–30 nmol/L	54
Durga et al., 2011 [41]	US/July 2006 to April 2007	Medical clinic	60 men with spinal cord injuries	TT < 325 ng/dL	43.3
Okun et al., 2002 [73]	US/not specified	Medical clinic	68 men with PD	FT < 70 pg/mL	35
Abbasi et al., 1994 [20]	US/not specified	Medical clinic	102 men with poststroke hemiplegia	TT < 2.5 percentile of the healthy old men	17

Miscellaneous diseases
Schatzl et al., 2000 [81]	Austria/October 1998 to May 1999	Medical clinic	312 men with lower urinary tract symptoms	T < 3 ng/mL	22.1
Rhoden et al., 2005 [77]	Brazil/January 2000 to December 2001	Medical clinic	746 urological patients	TT < 13.87 nmol/L	24.5
Taddesse et al., 2012 [86]	US/September 21 to December 21, 2010	Medical clinic	34 men with sickle cell	T ≤ 250 ng/dL	24
Okun et al., 2004 [72]	US/not specified	Chart review	118 men with PD + AD	PD + T < 325 ng/mL AD + T < 325 ng/mL	35 38
Moreno et al., 2009 [69]	US/January 2006 to January 2008	Medical chart review	121 men with Peyronie′s disease	TT < 300 ng/dL	29.5

CHD: chronic heart failure; CKD: chronic kidney disease; ED: erectile dysfunction; ESRD: end stage renal disease; MetS: metabolic syndrome; RA: rheumatoid arthritis; T2DM: type 2 diabetes mellitus; PD: Parkinson’s disease; AD: Alzheimer’s disease.

3.2.1. Population-Based Studies

The prevalence of hypogonadism in the 4 population-based studies ranged from 2.1% to 12.8% [2–5] (Table 2). Sample sizes in these studies ranged from 1,490 to 2,966 participants and the mean (SD) ages of the study participants ranged from 47.3 (12.5) to 59.15 (10.8) years. Mean age was not reported in one of the studies [3]; however, the sample was equally divided among men in their 40s, 50s, and 60s [3]. The studies were conducted in Europe (Belgium, Estonia, Hungary, Italy, Poland, Spain, Sweden, and UK) and USA.

The operational definition of hypogonadism used across studies varied considerably: the Study of Health in Pomerania (SHIP, 1997–2001) (Germany) [5] used the most liberal definition of hypogonadism (TT < 300 ng/dL, no symptom criteria) and reported the highest prevalence at 12.8%; the European Male Aging Study (EMAS, 2003–2005) [4] used the most stringent definition of symptomatic hypogonadism (TT < 317 ng/dL plus 3 specific symptoms of decreased frequency of morning erections, sexual thoughts, and erectile dysfunction) and reported the lowest prevalence at 2.1%. The Boston Area Community Health Survey (BACH, 2002–2005) [3] and the Massachusetts Male Aging Study (MMAS, 1987–1989) [2], both USA based, used similar operational definitions of symptomatic hypogonadism (TT cut-offs of <300 ng/dL plus ≥1 specific symptom or ≥2 nonspecific symptoms (BACH) and either TT <200 ng/dL plus ≥3 symptoms or TT 200–400 ng/dL plus FT <8.91 ng/dL plus ≥3 symptoms (see Table 2)) with reported prevalence of 5.6% (BACH) and 6.0% (MMAS), respectively.

3.2.2. Community-Based Studies

The prevalence of hypogonadism among the 3 community-based studies ranged from 9.5% to 31.2% (Table 2) [6–8]. All studies were cross-sectional and were conducted in Austria, China (Hong Kong), and Malaysia. The sample sizes ranged from 247 to 351 men, and the mean (SD) ages of men varied from 54 (NR) to 75.8 (0.4) years. The operational definition of hypogonadism varied considerably, with TT cut-offs ranging from <200 to <400, with and without low FT, and with and without symptoms. The highest prevalence (31.2%) was reported in a study of men with a mean age of 75.8 years [6].

3.2.3. Primary Care/Screening-Based Studies

Seven cross-sectional studies, conducted in Brazil, Chile, India, Italy, Taiwan, and USA, examined the prevalence of hypogonadism in a primary care or screening-based settings [9–15] (Table 2). Prevalence was higher than that observed in the general population surveys, ranging from 12% [10, 12] to 38.7% [13], with the majority around 20% [11, 12, 14, 15]. The sample sizes ranged from 96 to 2,719 men and the mean (SD) age of the participants in the studies ranged from 53.1 (NR) to 61.9 (7.5) years. Six of the studies used low TT to define hypogonadism [10–15] and one study used low bioavailable T and symptoms [9]. Using TT <300 ng/dL as a marker, prevalence was 19.3% [15], 19.8% [14], 24.1% [12], 24.2% [11], and 38.7% [13]. One study used a stricter TT threshold (TT < 230 ng/dL) with a lower resulting prevalence of 12% [10]. Adding symptoms as a criterion, the prevalence decreased from 24.1% to 12% [12] and from 24.2% to 20.4% [11].

3.2.4. Clinical Condition-Based Studies

A total of 78 studies were identified and assessed prevalence of hypogonadism among patients with specific medical conditions (Table 3). The prevalence varied considerably by medical condition. Hypogonadism occurred commonly among patients with type 2 diabetes mellitus (T2DM). Thirteen studies conducted in the UK, Australia, India, Italy, and USA showed the prevalence of hypogonadism in patients with T2DM ranging from 4.4% to above 45% [23, 25, 29, 36, 40, 45, 47, 48, 50, 56, 61, 71, 87] varying based on the definition of hypogonadism used: prevalence ranged from 4.4% to 36% using TT <8 mmol [23, 29, 45, 50, 56, 61, 71], from 24.5 to 43% using TT <10.4 mmol [36, 40, 47, 48], and from 34.7% to 45% using TT <12 mmol [25, 87]. Hypogonadism was also common among obese patients with prevalence ranging from 15% to 78.8% [22, 54, 74] and among patients with MetS, ranging from 30 to 35% [27, 62, 83]. When combined with obesity or metabolic syndrome (MetS), prevalence estimates among patients with T2DM were higher (51% [39] and 43% [70] for patients with T2DM and obesity and MetS, resp.).

Prevalence of hypogonadism in patients with cardiac disease [44, 55, 65, 67, 84, 94, 95], erectile dysfunction [24, 26, 32–35, 37, 49, 52, 59, 66, 85, 88], HIV [31, 38, 58, 78, 92, 93, 96], respiratory disease [51, 57, 64], depression [53, 68], cancer [43, 46, 63, 75, 76, 79, 80, 82, 91], rheumatoid arthritis [89], osteoporosis [30, 42], chronic kidney disease [21, 28, 60, 97], sickle cell disease [86], myopathies [20, 41, 52, 73, 90], urological diseases [77, 81], Peyronie’s disease [69], and Alzheimer’s and Parkinson’s disease [72] is detailed in Table 3.

3.2.5. Prevalence of Hypogonadism by Age

A total of 10 studies, conducted in Chile, China, Europe, Italy, and USA, examined changes in prevalence of hypogonadism with age (Table 4) [2, 3, 8, 9, 12, 13, 16–19]. Sample sizes ranged from 96 to 2,162 and mean (SD) ages ranged from 47.3 (12.5) to 61.9 (7.5) years. Five of the studies were population-based[2, 3, 17–19], one was community-based [8], and 4 were primary care-/screening-based [9, 12, 13, 16]; one was longitudinal [17] and 9 were cross-sectional [2, 3, 8, 9, 12, 13, 16, 18, 19].

Table 4. Prevalence of hypogonadism by age.

Author and year (study name)	Country and years of data collected	Study design	N	Age, mean (SD), and range	Definition of hypogonadism used	Prevalence, per age group, years (%)
Harman et al., 2001 (BLSA) [17]	USA, 40-year period	Population-based	890	53.8 (16.0), NR	TT < 325 ng/dL OR FT < 0.153 nmol/L	20–29	<5
						30–39	<5
						40–49	<10
						50–59	12
						60–69	19
						70–79	28
						>80	49^a

Wu et al., 2010 [19] (EMAS)	8 European countries, 2003–2005	Population-based	2966	59.15 (10.82), 40–79	TT < 317 ng/dL + FT < 220 pmol/L + ≥3 sexual symptoms^#	40–49	0.1
						50–59	0.6
						60–69	3.2
						70–79	5.1^b

Araujo et al., 2007 [3] (BACH)	USA, 2002–2005	Population-based	1475	47.3 (12.5)	TT < 300 ng/dL + FT < 5 ng/dL + ≥1 specific symptom or ≥2 nonspecific symptoms^†	30–39	1.1
						40–49	4.1
						50–59	8.1
						60–69	9.1
						70–79	22.1^c

Araujo et al., 2004 [2] (MMAS)	USA, 1987–1997	Population-based	1691	NR (NR), 40–70	TT < 200 ng/dL + ≥3 symptoms^††; OR: TT 200–400 ng/dL + FT < 8.91 ng/dL + ≥3 symptoms^††	40–49	4.1
						50–59	4.5
						60–70	9.4^d

Li et al., 2005 [18]	China, 2002-2003	Population-based study	1080	NR (NR), 20–>70	cFT < 0.3 nmol/L	40–49	13.0
						50–59	31.8
						60–69	30.1
						>70	46.7^e

Wong et al., 2006 [8]	China, 2003-2004	Community-based	252	54 (NR), 45–64	TT < 200 ng/dL + ≥3 of 7 symptoms OR: TT 200–400 ng/dL + FT < 0.3093 nmol/L + ≥3 of 7 symptoms	45–49	8.2
						50–54	6.3
						55–59	10
						60–65	16.7^f

Mulligan et al., 2006 [13] (HIM)	USA, 2003-2004	Primary care patients	2162	60.5 (10.33), 45–96	TT < 300 ng/dL	45–54	34
						55–64	40.2
						65–74	39.9
						75–84	45.5
						85+	50
						50–54	6.33
						55–59	10
						60–64	16.67^g

Liu et al., 2009 [12]	Taiwan, 2007-2008	Health screening clinic in a medical center	734	57.4 (6.7), 43–87	TT < 300 ng/dL	40–49	16.5
						50–59	23
						60–69	28.9
						≥70	37.2^h

Di Luigi et al., 2010 [16]	Italy, NR	Health screening clinic*	183	61.9 ± 7.5 years (range 50–75).	TT < 230 ng/dL	50–59	5.4
						60–69	10
						70–79	27.5ⁱ

Blümel et al., 2009 [9]	Chile, NR	Primary care-based (health services center)	96	55.1 ± 12.0 years (range 40–85 years)	BT < 198.4 ng/dL + symptoms**	40–54	17.9
						55–69	29.2
						≥70	66.7^j

TT: 200 ng/dL = 6.94 nmol/L; 230 ng/dL = 8 nmol/L; 300 ng/dL = 10.4 nmol/L; 317 ng/dL = 11 nmol/L; 325 ng/dL = 11.3 nmol/L; 350 ng/dL = 12 nmol/L; FT: 5 ng/dL = 0.17 nmol/L; 8.9 ng/dL = 0.3092 nmoL/L.
ADAM: androgen deficiency in the aging male; BACH: Boston Area Community Health; BT: bioavailable testosterone; cFT: calculated free testosterone; EMAS: European Male Aging Study; HIM: hypogonadism in males; MMAS: Massachusetts Male Aging Study; NR: not reported; SHIP: Study of Health in Pomerania; TT = total testosterone.
^aNo statistical test done; ^bno statistical test done; ^call pairwise comparisons, P < 0.05 over 70 versus all other age groups; ^dP values for trend <0.001; ^echi square P < 0.000; ^fnot significant; ^gno statistical test done; ^hP < 0.019 for trend; ⁱP < 0.01 versus age 50–59 and age 60–69; ^jP value for trend P < 0.0004.
^†Specific symptoms include low libido, erective dysfunction, or osteoporosis; the nonspecific symptoms include sleep disturbance, depressed mood, lethargy, or low physical performance.
^††Symptoms include loss of libido, erectile dysfunction, depression, lethargy, inability to concentrate, sleep disturbance, irritability, and depressed mood.
^#Specific signs/symptoms are low libido, erectile dysfunction, or osteoporosis.
*To evaluate risks associated with participation in sports in a group of healthy athletic men.
**Positive answer to items 1 or 7, or any 3 other questions on the ADAM questionnaire.

The prevalence of hypogonadism increased with each increasing age category [2, 3, 8, 9, 12, 13, 16–19], with the rare exception within certain age categories [3, 8] (Table 4). Three of the studies reported significant P values for trend [2, 9, 12], 3 reported significant differences between older and younger age categories [3, 9, 18], 2 studies did not conduct statistical analysis for differences in prevalence by age [17, 19], and one study was nonsignificant [8]. One cross-sectional study [13] reported a 17% (95% CI, 1.08–1.27) increase in risk of hypogonadism, for every 10-year increase in age. Prevalence ranged from approximately 0.1% to 16.5% among men aged 40–49, from 0.6% to 31.8% among men aged 50–59, from 3.2% to 30.1% among men aged 60–69, up to 66.7% among men of age ≥70 years [2, 3, 12, 17–19], and 49% in the study that assessed the 80+ age category [17] (not all studies used the same age cut-offs).

3.3. Incidence of Hypogonadism

In two population-based studies (SHIP [5] and BACH [2]), in which incidence was examined, the reported incidence was 12.3 cases per 1,000 person-years in the US and 11.7 cases per 1000 person-years in Germany.

3.4. Treatment Rates for Hypogonadism

The proportion of patients receiving treatment was defined as the percentage of men with hypogonadism who were receiving testosterone therapy. Only 4 studies were identified and reported treatment proportions: one population-based [98], one primary care-based [13], and 2 clinical condition-based studies [38, 79]. The population-based (BACH) and clinical-based studies (HIM) reported that 10% [98] and 12% [13] of patients were receiving treatment for hypogonadism, respectively. Among the clinical condition-based studies, 12.1% of 144 childhood cancer survivors [79] and 38% of 296 men with HIV were on treatment for hypogonadism [38].

4. Discussion

In this systematic review, we identified 97 studies that met our inclusion/exclusion criteria for assessing the epidemiology of hypogonadism. The prevalence of hypogonadism was high and varied according to the operational definition of hypogonadism used and the population studied. The prevalence of hypogonadism in the population-based, community-based, and primary care- or screening-based studies ranged from 2.1 to 12.8% [9–15], from 9.5 to 31.2% [9–18], and from 12 to 38.7% [9–15], respectively. The prevalence was higher among clinical-based populations with specific conditions. For example, among patients with T2DM, obesity, and MetS, the prevalence ranged from 4.4 to >50% [23, 25, 29, 36, 40, 45, 47, 48, 50, 56, 61, 71, 87], from 15 to 78.8% [22, 54, 74], and from 30 to 35% [27, 62, 83], respectively.

In most instances, studies showed a linear relationship between prevalence and the degree of liberalness in the operational definition of hypogonadism [4, 5, 7, 12]. For instance, Haring et al. [5] reported prevalence estimates below TT levels of 8.0, 8.7, 10.4, and 12.0 nmol/L, which were 3.4%, 4.5%, 12.8%, and 21.6%. The added criteria of symptoms typically ensued a lower prevalence due to increased stringency of diagnosis. Among the population- and community-based studies, those that used a more stringent definition of hypogonadism, which included symptoms and low T, reported the lowest prevalence, ranging from 2.1% to 9.52% [2–4, 7, 8], while those using a more liberal definition of hypogonadism (low T only) reported higher prevalence, ranging from 19.1% to 31.2% [5–7]. The association between definition of hypogonadism and prevalence was also apparent among the primary care-/health screening-based studies (12–39%).

Prevalence also varied by age. Hypogonadism was consistently found to increase with age for studies reporting data by age (REF), with one study citing an increase of 17% (95% CI, 1.08–1.27) in risk of hypogonadism, for every 10-year increase in age [13]. One study that had a considerably older cohort (mean age of 75.8 years) [6] reported the highest prevalence (31.2%) among community-based studies. It was estimated in a 2007 publication that there were 4.7 million American men aging 30–79 years with symptomatic androgen deficiency [3]. It was projected that there will be as many as 6.5 million American men aging 30–79 years with symptomatic hypogonadism by 2025, an increase of 38% from the year 2000 population estimates, due to an aging population [3].

Despite the significant prevalence of hypogonadism, data suggest that the vast majority of hypogonadal men are not receiving treatment for this condition [13, 98]. Reasons for this low treatment proportion have not been definitively determined; however, contributing factors may include inadequate knowledge base among physicians regarding hypogonadism and uncertainty regarding diagnostic criteria. The main indication for testosterone replacement therapy is sexual dysfunction with symptoms of reduced libido and/or erectile dysfunction. This may not be an issue to some men and therefore they are not treated or subjects may decline therapy. Also, individuals may not be able to afford therapy in countries where people have to pay for their prescriptions and healthcare. Furthermore, with the lack of long-term placebo-controlled safety studies, some clinicians may have concerns especially in the older man in regard to risks of prostate cancer and cardiovascular disease, even though there is limited evidence from current published studies or meta-analyses. The only study which did show a possible relationship between testosterone replacement therapy and cardiovascular events was the TOM trial [99]. However, this study involved the administration of larger testosterone doses than those used in normal clinical practice and was not sufficiently powered to detect an increase in cardiovascular events. A similar trial where routine doses of testosterone were used did not detect any increase in cardiovascular events [100].

Results of this review highlight the fact that there is no standardized definition used in the hypogonadism epidemiologic research. The hypogonadism literature reports wide-ranging prevalence based not only on the different populations or subpopulations studied, but also on the use of diverse biochemical cut points or varied choices of symptoms. The actual prevalence of disease that a clinician will treat in his or her office may in fact be higher than what we found in this review, as clinicians may use a more liberal definition of hypogonadism to base their treatment decisions on.

The studies in this review represented a wide geographic distribution with samples from USA, Europe, Asia, and South America. The prevalence of hypogonadism may vary by geographical location, as recently demonstrated in a large (n = 5003) international cohort of older men (>65 years of age) showing important geographical differences in concentrations of T [101]. However, differences in patient populations and operational definitions used across studies made it difficult to interpret the findings based on geography in the current review.

We can expect approximately 12 new cases of hypogonadism per 1,000 person-years [2, 5] and approximately 481,000 new cases of hypogonadism per year in US men aged 40–69 years [2]. It has been projected that there will be as many as 6.5 million US men aging 30–79 years with symptomatic AD by 2025 [3], an increase of 38% from the year 2000 population estimates, due to an aging population. While there is no conclusive evidence from this review that the prevalence of hypogonadism in the general population is increasing over time, there is evidence that the prevalence of hypogonadism does increase with age and with certain comorbidities such as T2DM and obesity, all of which are increasing in the general population. It follows that there may well be an increasing proportion of older men who will benefit from treatment for hypogonadism. As the proportion of the world’s population in the older ages continues to increase, the importance of studying, diagnosing, and treating male hypogonadism will also rise.

The mainstay treatment of low testosterone is testosterone replacement therapy (TRT), although there is indication that modification of diet and exercise regimes have the ability to improve testosterone levels [99]. Despite the significant prevalence of hypogonadism, self-reported data suggest that the vast majority of hypogonadal men are not receiving TRT treatment for this condition [13, 98]. Reasons for this low treatment proportion have not been definitively determined; however, contributing factors may include inadequate knowledge base among physicians regarding hypogonadism and uncertainty regarding diagnostic criteria. The main indication for TRT is sexual dysfunction, which, for some men, may not affect their daily lives, and therefore they choose not to be treated. Also, individuals may not be able to afford therapy in countries where people have to pay for their prescriptions and healthcare.

Another impeding factor for prescribing TRT may be a concern over the potential risk of cardiovascular disease and prostate cancer. The safety of TRT lacks examination in large, prospective, and adequately powered controlled trials [100]. Smaller studies have been published, some suggesting an association between testosterone replacement therapy and cardiovascular adverse events [100]. The TOM trial was terminated early due to an increased frequency of cardiovascular events in the men treated with testosterone [102]. However, this study involved the administration of larger testosterone doses than those used in normal clinical practice and was not sufficiently powered to detect an increase in cardiovascular events. A similar trial, which used routine doses of testosterone, did not detect any increase in cardiovascular events [103]. To address the question of safety and in lieu of long term, prospective safety data, the Endocrine Society Task Force on Testosterone Use in Adult Men commissioned a meta-analysis of randomized and observational studies with long-term follow-up in testosterone therapy in 2010. The analyses of 51 studies found no significant effect of TRT on mortality, prostate, or cardiovascular outcomes [100]. More recently, a retrospective database study of 8709 male veterans who underwent coronary angiography between 2005 and 2011 reported an increased risk (absolute risk increase: 5.8% (95% CI: −1.4% to 13.1%)) of experiencing an adverse cardiovascular event (all-cause mortality, MI, or ischemic stroke) among TRT versus nontreated men at 3 years after coronary angiography [104]. Although this study garnered media attention, it is limited by serious methodological concerns which put the results in question.

4.1. Limitations

A general limitation in hypogonadism research is the lack of a standardized operational definition of hypogonadism. Recently, professional societies have proposed operational definitions which include criteria of specific signs and symptoms plus biochemical low TT, typically defined as TT <300 ng/dL (<10.4 nmol/L) [1]. However, the literature is confounded by numerous studies using a variety of different definitions: some include sign and symptom criteria and others do not; biochemical TT thresholds used range from <8 nmol/L to <12 nmol/L, others use an FT criterion and no TT (as men with normal TT may be quite symptomatic in clinical due to low FT), and others use a TT and FT criterion. The varying definitions used make comparisons between studies difficult.

The proportions of patients receiving T therapy in the population were obtained from one population-based study and one primary care-based study, both of which reported on the number of participants who were receiving T therapy. Medication use, including use of T therapy, was assessed by patient self-report in the studies. Self-report of medication use is subjective and is at risk of both reporting bias and measurement bias. A more accurate measurement of treatment proportions could be obtained from chart review or commercial claims database study and may be an interesting objective for a future study.

As with all systematic reviews, publication bias, which can lead to bias if only positive studies or studies with a statistically significant difference are published, is an issue in this review. Another limitation of this review is that a quality appraisal of the individual studies was not conducted. Although methodological aspects of the individual studies, which may have influenced outcomes or comparisons between studies, were considered and commented on during the assessment of the evidence, a systematic quality assessment of the studies was not carried out.

5. Conclusions

This literature review suggests that there is potentially a significant burden of hypogonadism in the general population. The burden of hypogonadism increases with age and in the presence of certain clinical conditions, such as T2DM and obesity. Data suggested that the vast majority of hypogonadal men in the general population are not receiving treatment. This may be the result of underdiagnosis of the disease, due to lack of awareness by patients and/or physicians and the irregularities surrounding the diagnostic criteria.

Disclosure

The authors met criteria for authorship as recommended by the International Committee of Medical Journal Editors and are fully responsible for all content and editorial decisions and were involved in all stages of paper development. This original paper has not been previously presented in whole by the authors. A portion of the information has been presented as a poster entitled “The prevalence, incidence and treatment rates of hypogonadism in men across geographies: a systematic review of the literature” at the ISPOR, May 18–22, 2013, New Orleans, LA.

Conflict of Interests

Victoria Zarotsky and Wendy Carman are employees of Optum and were contracted by Merck & Co., Inc., to conduct this study. Donna Coffin is employee of Boolean Research Consulting Services who was contracted by Optum. Ming-Yi Huang is a Postdoctoral Fellow funded by Merck & Co., Inc. Puneet K. Singhal is employed by Merck & Co., Inc. T. Hugh Jones has received research grants from BayerHealthcare, UK, and honoraria for educational lectures and/or advisory boards from BayerHealthcare, Clarus, Lilly, Merck, and Prostrakan. T. Hugh Jones and Abraham Morgentaler have served as Consultants to Merck & Co., Inc., for this study.

Acknowledgments

This study was conducted by Optum located in Eden Prairie, Minnesota, USA, and was funded by Merck & Co., Inc., West Point, PA. This study was supported by Merck & Co., Inc.

References

1 Bhasin S., Cunningham G. R., Hayes F. J., Matsumoto A. M., Snyder P. J., Swerdloff R. S., and Montori V. M., Testosterone therapy in men with androgen deficiency syndromes: an endocrine society clinical practice guideline, The Journal of Clinical Endocrinology & Metabolism. (2010) 95, no. 6, 2536–2559, https://doi.org/10.1210/jc.2009-2354, 2-s2.0-77954409942.
10.1210/jc.2009-2354
CAS PubMed Web of Science® Google Scholar
2 Araujo A. B., O′Donnell A. B., Brambilla D. J., Simpson W. B., Longcope C., Matsumoto A. M., and McKinlay J. B., Prevalence and incidence of androgen deficiency in middle-aged and older men: Estimates from the Massachusetts male aging study, Journal of Clinical Endocrinology and Metabolism. (2004) 89, no. 12, 5920–5926, https://doi.org/10.1210/jc.2003-031719, 2-s2.0-10344243498.
10.1210/jc.2003-031719
CAS PubMed Web of Science® Google Scholar
3 Araujo A. B., Esche G. R., Kupelian V., O′Donnell A. B., Travison T. G., Williams R. E., Clark R. V., and McKinlay J. B., Prevalence of symptomatic androgen deficiency in men, Journal of Clinical Endocrinology and Metabolism. (2007) 92, no. 11, 4241–4247, https://doi.org/10.1210/jc.2007-1245, 2-s2.0-35948996162.
10.1210/jc.2007-1245
CAS PubMed Web of Science® Google Scholar
4 Tajar A., Huhtaniemi I. T., O′Neill T. W., Finn J. D., Pye S. R., Lee D. M., Bartfai G., Boonen S., Casanueva F. F. F., Forti G., Giwercman A., Han T. S., Kula K., Labrie F., Lean M. E. J., Pendleton N., Punab M., Vanderschueren D., and Wu F. C. W., Characteristics of androgen deficiency in Late-onset hypogonadism: results from the European Male Aging study (EMAS), Journal of Clinical Endocrinology and Metabolism. (2012) 97, no. 5, 1508–1516, https://doi.org/10.1210/jc.2011-2513, 2-s2.0-84860751541.
10.1210/jc.2011-2513
CAS PubMed Web of Science® Google Scholar
5 Haring R., Ittermann T., Völzke H., Krebs A., Zygmunt M., Felix S. B., Grabe H. J., Nauck M., and Wallaschofski H., Prevalence, incidence and risk factors of testosterone deficiency in a population-based cohort of men: results from the study of health in Pomerania, Aging Male. (2010) 13, no. 4, 247–257, https://doi.org/10.3109/13685538.2010.487553, 2-s2.0-78449296295.
10.3109/13685538.2010.487553
CAS PubMed Web of Science® Google Scholar
6 Ponholzer A., Madersbacher S., Rauchenwald M., Jungwirth S., Fischer P., and Tragl K., Vascular risk factors and their association to serum androgen levels in a population-based cohort of 75-year-old men over 5 years: results of the VITA study, World Journal of Urology. (2010) 28, no. 2, 209–214, https://doi.org/10.1007/s00345-009-0440-y, 2-s2.0-77952094935.
10.1007/s00345-009-0440-y
PubMed Web of Science® Google Scholar
7 Khoo E. M., Tan H. M., and Low W. Y., Erectile dysfunction and comorbidities in aging men: an urban cross-sectional study in Malaysia, Journal of Sexual Medicine. (2008) 5, no. 12, 2925–2934, https://doi.org/10.1111/j.1743-6109.2008.00988.x, 2-s2.0-57449105676.
10.1111/j.1743-6109.2008.00988.x
CAS PubMed Web of Science® Google Scholar
8 Wong S. Y. S., Chan D. C. C., Hong A., and Woo J., Prevalence of and risk factors for androgen deficiency in middle-aged men in Hong Kong, Metabolism: Clinical and Experimental. (2006) 55, no. 11, 1488–1494, https://doi.org/10.1016/j.metabol.2006.06.019, 2-s2.0-33749545774.
10.1016/j.metabol.2006.06.019
CAS PubMed Web of Science® Google Scholar
9 Blümel J. E., Chedraui P., Gili S. A., Navarro A., Valenzuela K., and Vallejo S., Is the Androgen Deficiency of Aging Men (ADAM) questionnaire useful for the screening of partial androgenic deficiency of aging men?, Maturitas. (2009) 63, no. 4, 365–368, https://doi.org/10.1016/j.maturitas.2009.04.004, 2-s2.0-68149160557.
10.1016/j.maturitas.2009.04.004
CAS PubMed Web of Science® Google Scholar
10 di Luigi L., Sgrò P., Fierro V., Bianchini S., Battistini G., Magini V., Jannini E. A., and Lenzi A., Prevalence of undiagnosed testosterone deficiency in aging athletes: does exercise training influence the symptoms of male hypogonadism?, Journal of Sexual Medicine. (2010) 7, no. 7, 2591–2601, https://doi.org/10.1111/j.1743-6109.2009.01694.x, 2-s2.0-77955126164.
10.1111/j.1743-6109.2009.01694.x
CAS PubMed Web of Science® Google Scholar
11 Goel A., Sinha R. J., Dalela D., Sankhwar S., and Singh V., Andropause in Indian men a preliminary cross-sectional study, Urology Journal. (2009) 6, no. 1, 40–46, 2-s2.0-64549109790.
PubMed Google Scholar
12 Liu C.-C., Wu W.-J., Lee Y.-C., Wang C., Ke H., Li W., Hsiao H., Yeh H., Li C., Chou Y., Huang C., and Huang S., The prevalence of and risk factors for androgen deficiency in aging Taiwanese men, Journal of Sexual Medicine. (2009) 6, no. 4, 936–946, https://doi.org/10.1111/j.1743-6109.2008.01171.x, 2-s2.0-63849204029.
10.1111/j.1743-6109.2008.01171.x
CAS PubMed Web of Science® Google Scholar
13 Mulligan T., Frick M. F., Zuraw Q. C., Stemhagen A., and McWhirter C., Prevalence of hypogonadism in males aged at least 45 years: The HIM study, International Journal of Clinical Practice. (2006) 60, no. 7, 762–769, https://doi.org/10.1111/j.1742-1241.2006.00992.x, 2-s2.0-33745108447.
10.1111/j.1742-1241.2006.00992.x
CAS PubMed Web of Science® Google Scholar
14 Júnior A. N., dos Santos Szelbracikowski S., Nardi A. C., and de Almeida J. C., Age-related testosterone decline in a Brazilian cohort of healthy military men, International Brazilian Journal of Urology. (2011) 37, no. 5, 591–597, https://doi.org/10.1590/S1677-55382011000500004, 2-s2.0-84860729460.
10.1590/S1677-55382011000500004
PubMed Google Scholar
15 Schneider H. J., Sievers C., Klotsche J., Böhler S., Pittrow D., Lehnert H., Wittchen H., and Stalla G. K., Prevalence of low male testosterone levels in primary care in Germany: cross-sectional results from the DETECT study, Clinical Endocrinology. (2009) 70, no. 3, 446–454, https://doi.org/10.1111/j.1365-2265.2008.03370.x, 2-s2.0-60349128958.
10.1111/j.1365-2265.2008.03370.x
CAS PubMed Web of Science® Google Scholar
16 Di Luigi L., Sgrò P., Fierro V., Bianchini S., Battistini G., Magini V., Jannini E. A., and Lenzi A., Prevalence of undiagnosed testosterone deficiency in aging athletes: does exercise training influence the symptoms of male hypogonadism?, Journal of Sexual Medicine. (2010) 7, no. 7, 2591–2601, https://doi.org/10.1111/j.1743-6109.2009.01694.x, 2-s2.0-77955126164.
10.1111/j.1743-6109.2009.01694.x
CAS PubMed Web of Science® Google Scholar
17 Harman S. M., Metter E. J., Tobin J. D., Pearson J., and Blackman M. R., Longitudinal effects of aging on serum total and free testosterone levels in healthy men, Journal of Clinical Endocrinology and Metabolism. (2001) 86, no. 2, 724–731, https://doi.org/10.1210/jc.86.2.724, 2-s2.0-0035097033.
10.1210/jcem.86.2.7219
CAS PubMed Web of Science® Google Scholar
18 Li J.-Y., Li X.-Y., Li M., Zhang G., Ma F., Liu Z., Zhang N., and Meng P., Decline of serum levels of free testosterone in aging healthy Chinese men, Aging Male. (2005) 8, no. 3-4, 203–206, https://doi.org/10.1080/13685530500356010, 2-s2.0-30344439107.
10.1080/13685530500356010
CAS PubMed Web of Science® Google Scholar
19 Wu F. C. W., Tajar A., Beynon J. M., Pye S. R., Silman A. J., Finn J. D., O′Neill T. W., Bartfai G., Casanueva F. F., Forti G., Giwercman A., Han T. S., Kula K., Lean M. E. J., Pendleton N., Punab M., Boonen S., Vanderschueren D., Labrie F., and Huhtaniemi I. T., Identification of late-onset hypogonadism in middle-aged and elderly men, The New England Journal of Medicine. (2010) 363, no. 2, 123–135, https://doi.org/10.1056/NEJMoa0911101, 2-s2.0-77954414397.
10.1056/NEJMoa0911101
CAS PubMed Web of Science® Google Scholar
20 Abbasi A., Mattson D. E., Cuisinier M., Schultz S., Rudman I., Drinka P., and Rudman D., Hyposomatomedinemia and hypogonadism in hemiplegic men who live in nursing homes, Archives of Physical Medicine and Rehabilitation. (1994) 75, no. 5, 594–599, 2-s2.0-0028233156.
10.1016/S0003-9993(21)01626-9
CAS PubMed Web of Science® Google Scholar
21 Albaaj F., Sivalingham M., Haynes P., McKinnon G., Foley R. N., Waldek S., O′Donoghue D. J., and Kalra P. A., Prevalence of hypogonadism in male patients with renal failure, Postgraduate Medical Journal. (2006) 82, no. 972, 693–696, https://doi.org/10.1136/pgmj.2006.045963, 2-s2.0-33751221329.
10.1136/pgmj.2006.045963
CAS PubMed Web of Science® Google Scholar
22 Allan C. A., Strauss B. J., Burger H. G., Forbes E. A., and McLachlan R. I., The association between obesity and the diagnosis of androgen deficiency in symptomatic ageing men, Medical Journal of Australia. (2006) 185, no. 8, 424–427, 2-s2.0-33750177610.
10.5694/j.1326-5377.2006.tb00639.x
PubMed Web of Science® Google Scholar
23 Anderson S. G., Heald A., Younger N., Bujawansa S., Narayanan R. P., McCulloch A., and Jones H., Screening for hypogonadism in diabetes 2008/9: results from the Cheshire Primary Care cohort, Primary Care Diabetes. (2012) 6, no. 2, 143–148, https://doi.org/10.1016/j.pcd.2011.07.006, 2-s2.0-84861332264.
10.1016/j.pcd.2011.07.006
PubMed Web of Science® Google Scholar
24 Arafa M., Zohdy W., Aboulsoud S., and Shamloul R., Prevalence of late-onset hypogonadism in men with type 2 diabetes mellitus, Andrologia. (2012) 44, no. 1, 756–763, https://doi.org/10.1111/j.1439-0272.2011.01262.x, 2-s2.0-84861496013.
10.1111/j.1439-0272.2011.01262.x
PubMed Google Scholar
25 Biswas M., Hampton D., Newcombe R. G., and Rees D. A., Total and free testosterone concentrations are strongly influenced by age and central obesity in men with type 1 and type 2 diabetes but correlate weakly with symptoms of androgen deficiency and diabetes-related quality of life, Clinical Endocrinology. (2012) 76, no. 5, 665–673, https://doi.org/10.1111/j.1365-2265.2011.04196.x, 2-s2.0-84859638581.
10.1111/j.1365-2265.2011.04196.x
CAS PubMed Web of Science® Google Scholar
26 Bunch T. J., Abraham D., Wang S., and Meikle A. W., Pituitary radiographic abnormalities and clinical correlates of hypogonadism in elderly males presenting with erectile dysfunction, Aging Male. (2002) 5, no. 1, 38–46, https://doi.org/10.1080/tam.5.1.38.46, 2-s2.0-0036267338.
10.1080/tam.5.1.38.46
CAS PubMed Google Scholar
27 Caldas A. D. A., Porto A. L., Motta L. D. C. D., and Casulari L. A., Relationship between insulin and hypogonadism in men with metabolic syndrome, Arquivos Brasileiros de Endocrinologia e Metabologia. (2009) 53, no. 8, 1005–1011, 2-s2.0-77954752423.
10.1590/S0004-27302009000800015
PubMed Google Scholar
28 Carrero J. J., Qureshi A. R., Nakashima A., Arver S., Parini P., Lindholm B., Bárány P., Heimbürger O., and Stenvinkel P., Prevalence and clinical implications of testosterone deficiency in men with end-stage renal disease, Nephrology Dialysis Transplantation. (2011) 26, no. 1, 184–190, https://doi.org/10.1093/ndt/gfq397, 2-s2.0-78650630599.
10.1093/ndt/gfq397
CAS PubMed Web of Science® Google Scholar
29 Chen R. Y. T., Wittert G. A., and Andrews G. R., Relative androgen deficiency in relation to obesity and metabolic status in older men, Diabetes, Obesity and Metabolism. (2006) 8, no. 4, 429–435, https://doi.org/10.1111/j.1463-1326.2005.00532.x, 2-s2.0-33748458429.
10.1111/j.1463-1326.2005.00532.x
CAS PubMed Web of Science® Google Scholar
30 Clapauch R., Braga D. J. D. C., Marinheiro L. P., Buksman S., and Schrank Y., Risk of late-onset hypogonadism (Andropause) in Brazilian men over 50 years of age with osteoporosis: usefulness of screening questionnaires, Arquivos Brasileiros de Endocrinologia e Metabologia. (2008) 52, no. 9, 1439–1447, https://doi.org/10.1590/S0004-27302008000900006, 2-s2.0-60149096172.
10.1590/S0004-27302008000900006
PubMed Web of Science® Google Scholar
31 Collazos J. and Esteban M., Has prolactin a role in the hypogonadal status of HIV-infected patients?, Journal of the International Association of Physicians in AIDS Care. (2009) 8, no. 1, 43–46, https://doi.org/10.1177/1545109708330908, 2-s2.0-67649383530.
10.1177/1545109708330908
Google Scholar
32 Corona G., Boddi V., Lotti F., Gacci M., Carini M., De Vita G., Sforza A., Forti G., Mannucci E., and Maggi M., The Relationship of testosterone to prostate-specific antigen in men with sexual dysfunction, Journal of Sexual Medicine. (2010) 7, no. 1, part 1, 284–292, https://doi.org/10.1111/j.1743-6109.2009.01549.x, 2-s2.0-74049096119.
10.1111/j.1743-6109.2009.01549.x
CAS PubMed Web of Science® Google Scholar
33 Corona G., Mannucci E., Lotti F., Boddi V., Jannini E. A., Fisher A. D., Monami M., Sforza A., Forti G., and Maggi M., Impairment of couple relationship in male patients with sexual dysfunction is associated with overt hypogonadism, Journal of Sexual Medicine. (2009) 6, no. 9, 2591–2600, https://doi.org/10.1111/j.1743-6109.2009.01352.x, 2-s2.0-69949089719.
10.1111/j.1743-6109.2009.01352.x
CAS PubMed Web of Science® Google Scholar
34 Corona G., Mannucci E., Lotti F., Fisher A. D., Bandini E., Balercia G., Forti G., and Maggi M., Pulse pressure, an index of arterial stiffness, is associated with androgen deficiency and impaired penile blood flow in men with ED, Journal of Sexual Medicine. (2009) 6, no. 1, 285–293, https://doi.org/10.1111/j.1743-6109.2008.01059.x, 2-s2.0-58149513375.
10.1111/j.1743-6109.2008.01059.x
CAS PubMed Web of Science® Google Scholar
35 Corona G., Mannucci E., Petrone L., Balercia G., Paggi F., Fisher A. D., Lotti F., Chiarini V., Fedele D., Forti G., and Maggi M., NCEP-ATPIII-defined metabolic syndrome, type 2 diabetes mellitus, and prevalence of hypogonadism in male patients with sexual dysfunction, Journal of Sexual Medicine. (2007) 4, no. 4, part 1, 1038–1045, https://doi.org/10.1111/j.1743-6109.2007.00529.x, 2-s2.0-34447531824.
10.1111/j.1743-6109.2007.00529.x
CAS PubMed Web of Science® Google Scholar
36 Corona G., Mannucci E., Petrone L., Ricca V., Balercia G., Mansani R., Chiarini V., Giommi R., Forti G., and Maggi M., Association of hypogonadism and type II diabetes in men attending an outpatient erectile dysfunction clinic, International Journal of Impotence Research. (2006) 18, no. 2, 190–197, https://doi.org/10.1038/sj.ijir.3901391, 2-s2.0-33644781487.
10.1038/sj.ijir.3901391
CAS PubMed Web of Science® Google Scholar
37 Corona G., Monami M., Boddi V., Cameron-Smith M., Fisher A. D., de Vita G., Melani C., Balzi D., Sforza A., Forti G., Mannucci E., and Maggi M., Low testosterone is associated with an increased risk of MACE lethality in subjects with erectile dysfunction, Journal of Sexual Medicine. (2010) 7, no. 4, 1557–1564, https://doi.org/10.1111/j.1743-6109.2009.01690.x, 2-s2.0-77953580935.
10.1111/j.1743-6109.2009.01690.x
CAS PubMed Web of Science® Google Scholar
38 Crum-Cianflone N. F., Bavaro M., Hale B., Amling C., Truett A., Brandt C., Pope B., Furtek K., Medina S., and Wallace M. R., Erectile dysfunction and hypogonadism among men with HIV, AIDS Patient Care and STDs. (2007) 21, no. 1, 9–19, https://doi.org/10.1089/apc.2006.0071, 2-s2.0-33846828729.
10.1089/apc.2006.0071
PubMed Web of Science® Google Scholar
39 Dhindsa S., Miller M. G., McWhirter C. L., Mager D. E., Ghanim H., Chaudhuri A., and Dandona P., Testosterone concentrations in diabetic and nondiabetic obese men, Diabetes Care. (2010) 33, no. 6, 1186–1192, https://doi.org/10.2337/dc10-er08a, 2-s2.0-77958156616.
10.2337/dc09-1649
CAS PubMed Web of Science® Google Scholar
40 Dhindsa S., Prabhakar S., Sethi M., Bandyopadhyay A., Chaudhuri A., and Dandona P., Frequent occurrence of hypogonadotropic hypogonadism in type 2 diabetes, Journal of Clinical Endocrinology and Metabolism. (2004) 89, no. 11, 5462–5468, https://doi.org/10.1210/jc.2004-0804, 2-s2.0-8744228132.
10.1210/jc.2004-0804
CAS PubMed Web of Science® Google Scholar
41 Durga A., Sepahpanah F., Regozzi M., Hastings J., and Crane D. A., Prevalence of testosterone deficiency after spinal cord injury, PM & R. (2011) 3, no. 10, 929–932, https://doi.org/10.1016/j.pmrj.2011.07.008, 2-s2.0-84857497964.
10.1016/j.pmrj.2011.07.008
PubMed Web of Science® Google Scholar
42 Fink H. A., Ewing S. K., Ensrud K. E., Barrett-Connor E., Taylor B. C., Cauley J. A., and Orwoll E. S., Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men, Journal of Clinical Endocrinology and Metabolism. (2006) 91, no. 10, 3908–3915, https://doi.org/10.1210/jc.2006-0173, 2-s2.0-33749541914.
10.1210/jc.2006-0173
CAS PubMed Web of Science® Google Scholar
43 Fleishman S. B., Khan H., Homel P., Suhail M. F., Strebel-Amrhein R., Mohammad F., Mahajan D., Rosenwald V., Guarino M. J., Mirzoyev T., Wozniak T. F., and Suppiah K., Testosterone levels and quality of life in diverse male patients with cancers unrelated to androgens, Journal of Clinical Oncology. (2010) 28, no. 34, 5054–5060, https://doi.org/10.1200/JCO.2010.30.3818, 2-s2.0-79951888674.
10.1200/JCO.2010.30.3818
CAS PubMed Web of Science® Google Scholar
44 Florvaag A., Oberle V., Fritzenwanger M., Kretschmar D., Betge S., Goebel B., Barz D., Ferrari M., Figulla H. R., Franz M., and Jung C., Testosterone deficiency in male heart failure patients and its effect on endothelial progenitor cells, Aging Male. (2012) 15, no. 3, 180–186, https://doi.org/10.3109/13685538.2012.702361, 2-s2.0-84864862636.
10.3109/13685538.2012.702361
CAS PubMed Web of Science® Google Scholar
45 Ganesh H. K., Sarathi H. A. V., George J., Shivane V. K., Bandgar T., Menon P. S., and Shah N. S., Prevalence of hypogonadism in patients with type 2 diabetes mellitus in an Asian Indian study group, Endocrine Practice. (2009) 15, no. 6, 513–520, https://doi.org/10.4158/EP09035.ORR, 2-s2.0-75549083438.
10.4158/EP09035.ORR
PubMed Web of Science® Google Scholar
46 Greenfield D. M., Walters S. J., Coleman R. E., Hancock B. W., Eastell R., Davies H. A., Snowden J. A., Derogatis L., Shalet S. M., and Ross R. J. M., Prevalence and consequences of androgen deficiency in young male cancer survivors in a controlled cross-sectional study, Journal of Clinical Endocrinology and Metabolism. (2007) 92, no. 9, 3476–3482, https://doi.org/10.1210/jc.2006-2744, 2-s2.0-34548794429.
10.1210/jc.2006-2744
CAS PubMed Web of Science® Google Scholar
47 Grossmann M., Panagiotopolous S., Sharpe K., MacIsaac R. J., Clarke S., Zajac J. D., Jerums G., and Thomas M. C., Low testosterone and anaemia in men with type 2 diabetes, Clinical Endocrinology. (2009) 70, no. 4, 547–553, https://doi.org/10.1111/j.1365-2265.2008.03357.x, 2-s2.0-61449237409.
10.1111/j.1365-2265.2008.03357.x
CAS PubMed Web of Science® Google Scholar
48 Grossmann M., Thomas M. C., Panagiotopoulos S., Sharpe K., MacIsaac R. J., Clarke S., Zajac J. D., and Jerums G., Low testosterone levels are common and associated with insulin resistance in men with diabetes, Journal of Clinical Endocrinology and Metabolism. (2008) 93, no. 5, 1834–1840, https://doi.org/10.1210/jc.2007-2177, 2-s2.0-43249128538.
10.1210/jc.2007-2177
CAS PubMed Web of Science® Google Scholar
49 Guay A., Seftel A. D., and Traish A., Hypogonadism in men with erectile dysfunction may be related to a host of chronic illnesses, International Journal of Impotence Research. (2010) 22, no. 1, 9–19, https://doi.org/10.1038/ijir.2009.46, 2-s2.0-75149172663.
10.1038/ijir.2009.46
CAS PubMed Web of Science® Google Scholar
50 Hackett G. I., Cole N. S., Deshpande A. A., Popple M. D., Kennedy D., and Wilkinson P., Biochemical hypogonadism in men with type 2 diabetes in primary care practice, British Journal of Diabetes and Vascular Disease. (2009) 9, no. 5, 226–231, https://doi.org/10.1177/1474651409342635, 2-s2.0-74549224371.
10.1177/1474651409342635
CAS Google Scholar
51 Halabi S., Collins E. G., Thorevska N., Tobin M. J., and Laghi F., Relationship between depressive symptoms and hypogonadism in men with COPD, COPD: Journal of Chronic Obstructive Pulmonary Disease. (2011) 8, no. 5, 346–353, https://doi.org/10.3109/15412555.2011.594465, 2-s2.0-80053076035.
10.3109/15412555.2011.594465
Google Scholar
52 Hamidi M. A., Heidarzadeh A., Akbari P. N., Khosravi D. F., and Hamidi M. Z., A survey on relative frequency of metabolic syndrome and testosterone deficiency in men with erectile dysfunction, International Urology and Nephrology. (2012) 44, no. 3, 667–672, https://doi.org/10.1007/s11255-011-0086-8, 2-s2.0-84863712116.
10.1007/s11255-011-0086-8
PubMed Google Scholar
53 Hintikka J., Niskanen L., Koivumaa-Honkanen H., Tolmunen T., Honkalampi K., Lehto S. M., and Viinamäki H., Hypogonadism, decreased sexual desire, and long-term depression in middle-aged men, Journal of Sexual Medicine. (2009) 6, no. 7, 2049–2057, https://doi.org/10.1111/j.1743-6109.2009.01299.x, 2-s2.0-67649992010.
10.1111/j.1743-6109.2009.01299.x
CAS PubMed Web of Science® Google Scholar
54 Hofstra J., Loves S., van Wageningen B., Ruinemans-Koerts J., Janssen I., and de Boer H., High prevalence of hypogonadotropic hypogonadism in men referred for obesity treatment, Netherlands Journal of Medicine. (2008) 66, no. 3, 103–109, 2-s2.0-41349122914.
CAS PubMed Web of Science® Google Scholar
55 Jankowska E. A., Biel B., Majda J., Szklarska A., Lopuszanska M., Medras M., Anker S. D., Banasiak W., Poole-Wilson P. A., and Ponikowski P., Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival, Circulation. (2006) 114, no. 17, 1829–1837, https://doi.org/10.1161/CIRCULATIONAHA.106.649426, 2-s2.0-33750548421.
10.1161/CIRCULATIONAHA.106.649426
CAS PubMed Web of Science® Google Scholar
56 Kapoor D., Aldred H., Clark S., Channer K. S., and Jones T. H., Clinical and biochemical assessment of hypogonadism in men with type 2 diabetes: Correlations with bioavailable testosterone and visceral adiposity, Diabetes Care. (2007) 30, no. 4, 911–917, https://doi.org/10.2337/dc06-1426, 2-s2.0-34147104552.
10.2337/dc06-1426
CAS PubMed Web of Science® Google Scholar
57 Kirbas G., Abakay A., Topcu F., Kaplan A., Unlu M., and Peker Y., Obstructive sleep apnoea, cigarette smoking and serum testosterone levels in a male sleep clinic cohort, Journal of International Medical Research. (2007) 35, no. 1, 38–45.
10.1177/147323000703500103
CAS PubMed Web of Science® Google Scholar
58 Klein R. S., Lo Y., Santoro N., and Dobs A. S., Androgen levels in older men who have or who are at risk of acquiring HIV infection, Clinical Infectious Diseases. (2005) 41, no. 12, 1794–1803, https://doi.org/10.1086/498311, 2-s2.0-28744439315.
10.1086/498311
CAS PubMed Web of Science® Google Scholar
59 Köhler T. S., Kim J., Feia K., Bodie J., Johnson N., Makhlouf A., and Monga M., Prevalence of androgen deficiency in men with erectile dysfunction, Urology. (2008) 71, no. 4, 693–697, https://doi.org/10.1016/j.urology.2007.11.073, 2-s2.0-41149171607.
10.1016/j.urology.2007.11.073
PubMed Web of Science® Google Scholar
60 Kyriazis J., Tzanakis I., Stylianou K., Katsipi I., Moisiadis D., Papadaki A., Mavroeidi V., Kagia S., Karkavitsas N., and Daphnis E., Low serum testosterone, arterial stiffness and mortality in male haemodialysis patients, Nephrology Dialysis Transplantation. (2011) 26, no. 9, 2971–2977, https://doi.org/10.1093/ndt/gfq847, 2-s2.0-80053203340.
10.1093/ndt/gfq847
CAS PubMed Web of Science® Google Scholar
61 la Vignera S., Calogero A. E., Condorelli R., Lanzafame F., Giammusso B., and Vicari E., Andrological characterization of the patient with diabetes mellitus, Minerva Endocrinologica. (2009) 34, no. 1, 1–9, 2-s2.0-67650360231.
CAS PubMed Web of Science® Google Scholar
62 Laaksonen D. E., Niskanen L., Punnonen K., Nyyssönen K., Tuomainen T., Valkonen V., and Salonen J. T., The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study, Journal of Clinical Endocrinology and Metabolism. (2005) 90, no. 2, 712–719, https://doi.org/10.1210/jc.2004-0970, 2-s2.0-14044277032.
10.1210/jc.2004-0970
CAS PubMed Web of Science® Google Scholar
63 Lackner J. E., Märk I., Schatzl G., Marberger M., and Kratzik C., Hypogonadism and androgen deficiency symptoms in testicular cancer survivors, Urology. (2007) 69, no. 4, 754–758, https://doi.org/10.1016/j.urology.2007.01.002, 2-s2.0-34147133930.
10.1016/j.urology.2007.01.002
PubMed Web of Science® Google Scholar
64 Laghi F., Antonescu-Turcu A., Collins E., Segal J., Tobin D. E., Jubran A., and Tobin M. J., Hypogonadism in men with chronic obstructive pulmonary disease: prevalence and quality of life, The American Journal of Respiratory and Critical Care Medicine. (2005) 171, no. 7, 728–733, https://doi.org/10.1164/rccm.200501-037OC, 2-s2.0-16344387528.
10.1164/rccm.200501-037OC
PubMed Web of Science® Google Scholar
65 Lerchbaum E., Pilz S., Boehm B. O., Grammer T. B., Obermayer-Pietsch B., and März W., Combination of low free testosterone and low vitamin D predicts mortality in older men referred for coronary angiography, Clinical Endocrinology. (2012) 77, no. 3, 475–483, https://doi.org/10.1111/j.1365-2265.2012.04371.x, 2-s2.0-84865023727.
10.1111/j.1365-2265.2012.04371.x
CAS PubMed Web of Science® Google Scholar
66 Makhlouf A. A., Mohamed M. A., Seftel A. D., and Neiderberger C., Hypogonadism is associated with overt depression symptoms in men with erectile dysfunction, International Journal of Impotence Research. (2008) 20, no. 2, 157–161, https://doi.org/10.1038/sj.ijir.3901576, 2-s2.0-40649105059.
10.1038/sj.ijir.3901576
CAS PubMed Web of Science® Google Scholar
67 Malkin C. J., Pugh P. J., Morris P. D., Asif S., Jones T. H., and Channer K. S., Low serum testosterone and increased mortality in men with coronary heart disease, Heart. (2010) 96, no. 22, 1821–1825, https://doi.org/10.1136/hrt.2010.195412, 2-s2.0-78349305091.
10.1136/hrt.2010.195412
CAS PubMed Web of Science® Google Scholar
68 McIntyre R. S., Mancini D., Eisfeld B. S., Soczynska J. K., Grupp L., Konarski J. Z., and Kennedy S. H., Calculated bioavailable testosterone levels and depression in middle-aged men, Psychoneuroendocrinology. (2006) 31, no. 9, 1029–1035, https://doi.org/10.1016/j.psyneuen.2006.06.005, 2-s2.0-33749250347.
10.1016/j.psyneuen.2006.06.005
CAS PubMed Web of Science® Google Scholar
69 Moreno S. A. and Morgentaler A., Testosterone deficiency and Peyronie′s disease: pilot data suggesting a significant relationship, Journal of Sexual Medicine. (2009) 6, no. 6, 1729–1735, https://doi.org/10.1111/j.1743-6109.2009.01250.x, 2-s2.0-66649093844.
10.1111/j.1743-6109.2009.01250.x
CAS PubMed Web of Science® Google Scholar
70 Ogbera A. O., Relationship between serum testosterone levels and features of the metabolic syndrome defining criteria in patients with type 2 diabetes mellitus, West African Journal of Medicine. (2011) 30, no. 4, 277–281, 2-s2.0-84862279647.
CAS PubMed Google Scholar
71 Ogbera O. A., Sonny C., Olufemi F., and Wale A., Hypogonadism and subnormal total testosterone levels in men with type 2 diabetes mellitus, Journal of the College of Physicians and Surgeons Pakistan. (2011) 21, no. 9, 517–521, 2-s2.0-80052713797.
PubMed Web of Science® Google Scholar
72 Okun M. S., DeLong M. R., Hanfelt J., Gearing M., and Levey A., Plasma testosterone levels in Alzheimer and Parkinson diseases, Neurology. (2004) 62, no. 3, 411–413, https://doi.org/10.1212/01.WNL.0000106840.72938.84, 2-s2.0-1042276576.
10.1212/01.WNL.0000106840.72938.84
CAS PubMed Web of Science® Google Scholar
73 Okun M. S., McDonald W. M., and Delong M. R., Refractory nonmotor symptoms in male patients with Parkinson disease due to testosterone deficiency: a common unrecognized comorbidity, Archives of Neurology. (2002) 59, no. 5, 807–811, https://doi.org/10.1001/archneur.59.5.807, 2-s2.0-0036091450.
10.1001/archneur.59.5.807
PubMed Web of Science® Google Scholar
74 Pellitero S., Olaizola I., Alastrue A., Martínez E., Granada M. L., Balibrea J. M., Moreno P., Serra A., Navarro-Díaz M., Romero R., and Puig-Domingo M., Hypogonadotropic hypogonadism in morbidly obese males is reversed after bariatric surgery, Obesity Surgery. (2012) 22, no. 12, 1835–1842, https://doi.org/10.1007/s11695-012-0734-9, 2-s2.0-84878824993.
10.1007/s11695-012-0734-9
PubMed Web of Science® Google Scholar
75 Pühse G., Secker A., Kemper S., Hertle L., and Kliesch S., Testosterone deficiency in testicular germ-cell cancer patients is not influenced by oncological treatment, International Journal of Andrology. (2011) 34, no. 5, part 2, e351–e357, https://doi.org/10.1111/j.1365-2605.2010.01123.x, 2-s2.0-80053384082.
10.1111/j.1365-2605.2010.01123.x
CAS PubMed Web of Science® Google Scholar
76 Rajagopal A., Vassilopoulou-Sellin R., Palmer J. L., Kaur G., and Bruera E., Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids, Cancer. (2004) 100, no. 4, 851–858, https://doi.org/10.1002/cncr.20028, 2-s2.0-0842347571.
10.1002/cncr.20028
CAS PubMed Web of Science® Google Scholar
77 Rhoden E. L., Ribeiro E. P., Teloken C., and Souto C. A. V., Diabetes mellitus is associated with subnormal serum levels of free testosterone in men, BJU International. (2005) 96, no. 6, 867–870, https://doi.org/10.1111/j.1464-410X.2005.05728.x, 2-s2.0-25844442320.
10.1111/j.1464-410X.2005.05728.x
CAS PubMed Web of Science® Google Scholar
78 Rietschel P., Corcoran C., Stanley T., Basgoz N., Klibanski A., and Grinspoon S., Prevalence of hypogonadism among men with weight loss related to human immunodeficiency virus infection who were receiving highly active antiretroviral therapy, Clinical Infectious Diseases. (2000) 31, no. 5, 1240–1244, https://doi.org/10.1086/317457, 2-s2.0-0034456965.
10.1086/317457
CAS PubMed Web of Science® Google Scholar
79 Romerius P., Ståhl O., Moëll C., Relander T., Cavallin-Ståhl E., Wiebe T., Giwercman Y. L., and Giwercman A., Hypogonadism risk in men treated for childhood cancer, Journal of Clinical Endocrinology and Metabolism. (2009) 94, no. 11, 4180–4186, https://doi.org/10.1210/jc.2009-0337, 2-s2.0-70449101092.
10.1210/jc.2009-0337
CAS PubMed Web of Science® Google Scholar
80 Salonia A., Gallina A., Briganti A., Abdollah F., Suardi N., Capitanio U., Colombo R., Freschi M., Rigatti P., and Montorsi F., Preoperative hypogonadism is not an independent predictor of high-risk disease in patients undergoing radical prostatectomy, Cancer. (2011) 117, no. 17, 3953–3962, https://doi.org/10.1002/cncr.25985, 2-s2.0-79960258328.
10.1002/cncr.25985
PubMed Web of Science® Google Scholar
81 Schatzl G., Brössner C., Schmid S., Kugler W., Roehrich M., Treu T., Szalay A., Djavan B., Schmidbauer C. P., Söregi S., and Madersbacher S., Endocrine status in elderly men with lower urinary tract symptoms: correlation of age, hormonal status, and lower urinary tract function, Urology. (2000) 55, no. 3, 397–402, https://doi.org/10.1016/S0090-4295(99)00473-2, 2-s2.0-0343048346.
10.1016/S0090-4295(99)00473-2
CAS PubMed Web of Science® Google Scholar
82 Schatzl G., Madersbacher S., Thurridl T., Waldmüller J., Kramer G., Haitel A., and Marberger M., High-grade prostate cancer is associated with low serum testosterone levels, Prostate. (2001) 47, no. 1, 52–58, https://doi.org/10.1002/pros.1046, 2-s2.0-0035313592.
10.1002/pros.1046
CAS PubMed Web of Science® Google Scholar
83 Singh S. K., Goyal R., and Pratyush D. D., Is hypoandrogenemia a component of metabolic syndrome in males?, Experimental and Clinical Endocrinology & Diabetes. (2011) 119, no. 1, 30–35, https://doi.org/10.1055/s-0030-1261918, 2-s2.0-78651433474.
10.1055/s-0030-1261918
CAS PubMed Web of Science® Google Scholar
84 Serra E., Porcu M., Minerba L., Serra S., Oppo A., Orrù P., Corda M., Atzeni F., Cappai A., and Mariotti S., High prevalence of male hypogonadism and sexual dysfunction in long-term clinically stable heart transplantation recipients, International Journal of Cardiology. (2012) 155, no. 3, 476–477, https://doi.org/10.1016/j.ijcard.2011.12.075, 2-s2.0-84857793495.
10.1016/j.ijcard.2011.12.075
PubMed Google Scholar
85 Somani B., Khan S., and Donat R., Screening for metabolic syndrome and testosterone deficiency in patients with erectile dysfunction: results from the first UK prospective study, BJU International. (2010) 106, no. 5, 688–690, https://doi.org/10.1111/j.1464-410X.2009.09145.x, 2-s2.0-77955897292.
10.1111/j.1464-410X.2009.09145.x
CAS PubMed Web of Science® Google Scholar
86 Taddesse A., Woldie I. L., Khana P., Swerdlow P. S., Chu J.-., Abrams J., and Abou-Samra A.-., Hypogonadism in patients with sickle cell disease: central or peripheral?, Acta Haematologica. (2012) 128, no. 2, 65–68, https://doi.org/10.1159/000337344, 2-s2.0-84861816068.
10.1159/000337344
CAS PubMed Web of Science® Google Scholar
87 Talukder S. K., Afsana F., and Khan S. J., Metabolic syndrome in men with sexual dysfunction, Diabetes and Metabolic Syndrome: Clinical Research and Reviews. (2010) 4, no. 3, 143–149, https://doi.org/10.1016/j.dsx.2010.07.001, 2-s2.0-77956182355.
10.1016/j.dsx.2010.07.001
Google Scholar
88 Tan W. S., Ng C. J., Khoo E. M., Low W., and Tan H. M., The triad of erectile dysfunction, testosterone deficiency syndrome and metabolic syndrome: findings from a multi-ethnic Asian men study (The Subang Men′s Health Study), The Aging Male. (2011) 14, no. 4, 231–236, 2-s2.0-84858394112.
10.3109/13685538.2011.597463
CAS PubMed Web of Science® Google Scholar
89 Tengstrand B., Carlström K., and Hafström I., Bioavailable testosterone in men with rheumatoid arthritis—high frequency of hypogonadism, Rheumatology. (2002) 41, no. 3, 285–289, https://doi.org/10.1093/rheumatology/41.3.285, 2-s2.0-0036100737.
10.1093/rheumatology/41.3.285
CAS PubMed Web of Science® Google Scholar
90 Travison T. G., Shackelton R., Araujo A. B., Hall S. A., Williams R. E., Clark R. V., O′Donnell A. B., and McKinlay J. B., The natural history of symptomatic androgen deficiency in men: onset, progression, and spontaneous remission, Journal of the American Geriatrics Society. (2008) 56, no. 5, 831–839, https://doi.org/10.1111/j.1532-5415.2008.01679.x, 2-s2.0-43249087232.
10.1111/j.1532-5415.2008.01679.x
PubMed Web of Science® Google Scholar
91 Tromp K., Claessens J. J. M., Knijnenburg S. L., Van Der Pal H. J. H., Van Leeuwen F. E., Caron H. N., Beerendonk C. C. M., and Kremer L. C. M., Reproductive status in adult male long-term survivors of childhood cancer, Human Reproduction. (2011) 26, no. 7, 1775–1783, https://doi.org/10.1093/humrep/der113, 2-s2.0-79959477340.
10.1093/humrep/der113
CAS PubMed Web of Science® Google Scholar
92 Wagner G., Rabkin J. G., and Rabkin R., Illness stage, concurrent medications, and other correlates of low testosterone in men with HIV illness, Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology. (1995) 8, no. 2, 204–207, 2-s2.0-0028911571.
10.1097/00042560-199502000-00013
CAS PubMed Web of Science® Google Scholar
93 Wahlstrom J. T., Tang A., Cofrancesco J., ShahN.Jr., and Dobs A. S., Gonadal hormone levels in injection drug users, Drug and Alcohol Dependence. (2000) 60, no. 3, 311–313, https://doi.org/10.1016/S0376-8716(99)00156-8, 2-s2.0-0034634645.
10.1016/S0376-8716(99)00156-8
CAS PubMed Google Scholar
94 Wang X.-F., Wang J.-H., and Li J.-Y., Androgen deficiency in elderly men with systolic chronic heart failure, Journal of Geriatric Cardiology. (2010) 7, no. 3-4, 138–142, 2-s2.0-79956283610.
CAS Web of Science® Google Scholar
95 Wehr E., Pilz S., Boehm B. O., März W., and Obermayer-Pietsch B., Association of vitamin D status with serum androgen levels in men, Clinical Endocrinology. (2010) 73, no. 2, 243–248, https://doi.org/10.1111/j.1365-2265.2009.03777.x, 2-s2.0-77954869166.
10.1111/j.1365-2265.2009.03777.x
CAS PubMed Web of Science® Google Scholar
96 Wunder D. M., Bersinger N. A., Fux C. A., Mueller N. J., Hirschel B., Cavassini M., Elzi L., Schmid P., Bernasconi E., Mueller B., Furrer H., Battegay M., Bernasconi E., Böni J., Bucher H., Bürgisser P., Cattacin S., Cavassini M., Dubs R., Egger M., Elzi L., Erb P., Fischer M., Flepp M., Fontana A., Francioli P., Furrer H., Gorgievski M., Günthard H., Hirschel B., Hösli I., Kahlert C., Kaiser L., Karrer U., Keiser O., Kind C., Klimkait T., Ledergerber B., Martinez B., Müller N., Nadal D., Opravil M., Paccaud F., Pantaleo G., Perrin L., Piffaretti J.-., Rickenbach M., Rudin C., Schmid P., Schultze D., Schüpbach J., Speck R., Taffé P., Tarr P., Telenti A., Trkola A., Vernazza P., Weber R., and Yerly S., Hypogonadism in HIV-1-infected men is common and does not resolve during antiretroviral therapy, Antiviral Therapy. (2007) 12, no. 2, 261–265, 2-s2.0-34147102356.
10.1177/135965350701200215
CAS PubMed Web of Science® Google Scholar
97 Yilmaz M. I., Sonmez A., Qureshi A. R., Saglam M., Stenvinkel P., Yaman H., Eyileten T., Caglar K., Oguz Y., Taslipinar A., Vural A., Gok M., Unal H. U., Yenicesu M., and Carrero J. J., Endogenous testosterone, endothelial dysfunction, and cardiovascular events in men with nondialysis chronic kidney disease, Clinical Journal of the American Society of Nephrology. (2011) 6, no. 7, 1617–1625, https://doi.org/10.2215/CJN.10681210, 2-s2.0-79960305157.
10.2215/CJN.10681210
CAS PubMed Web of Science® Google Scholar
98 Hall S. A., Araujo A. B., Esche G. R., Williams R. E., Clark R. V., Travison T. G., and McKinlay J. B., Treatment of symptomatic androgen deficiency: results from the Boston Area Community Health Survey, Archives of Internal Medicine. (2008) 168, no. 10, 1070–1076, https://doi.org/10.1001/archinte.168.10.1070, 2-s2.0-44349169518.
10.1001/archinte.168.10.1070
CAS PubMed Web of Science® Google Scholar
99 Dandona P. and Rosenberg M. T., A practical guide to male hypogonadism in the primary care setting, International Journal of Clinical Practice. (2010) 64, no. 6, 682–696, https://doi.org/10.1111/j.1742-1241.2010.02355.x, 2-s2.0-77950644692.
10.1111/j.1742-1241.2010.02355.x
CAS PubMed Web of Science® Google Scholar
100 Fernández-Balsells M., Murad M., Lane M. et al., Clinical review 1: adverse effects of testosterone therapy in adult men: a systematic review and meta-analysis, Journal of Clinical Endocrinology and Metabolism. (2010) 95, no. 6, 2560–2575, https://doi.org/10.1210/jc.2009-2575.
10.1210/jc.2009-2575
CAS PubMed Web of Science® Google Scholar
101 Orwoll E. S., Nielson C. M., Labrie F., Barrett-Connor E., Cauley J. A., Cummings S. R., Ensrud K., Karlsson M., Lau E., Leung P. C., Lunggren Ö., Mellström D., Patrick A. L., Stefanick M. L., Nakamura K., Yoshimura N., Zmuda J., Vandenput L., and Ohlsson C., Evidence for geographical and racial variation in serum sex steroid levels in older men, Journal of Clinical Endocrinology and Metabolism. (2010) 95, no. 10, E151–E160, https://doi.org/10.1210/jc.2009-2435, 2-s2.0-77957785833.
10.1210/jc.2009-2435
CAS PubMed Web of Science® Google Scholar
102 Basaria S., Coviello A. D., Travison T. G., Storer T. W., Farwell W. R., Jette A. M., Eder R., Tennstedt S., Ulloor J., Zhang A., Choong K., Lakshman K. M., Mazer N. A., Miciek R., Krasnoff J., Elmi A., Knapp P. E., Brooks B., Appleman E., Aggarwal S., Bhasin G., Hede-Brierley L., Bhatia A., Collins L., LeBrasseur N., Fiore L. D., and Bhasin S., Adverse events associated with testosterone administration, The New England Journal of Medicine. (2010) 363, no. 2, 109–122, https://doi.org/10.1056/NEJMoa1000485, 2-s2.0-77954421915.
10.1056/NEJMoa1000485
CAS PubMed Web of Science® Google Scholar
103 Srinivas-Shankar U., Roberts S. A., Connolly M. J., O′Connell M. D. L., Adams J. E., Oldham J. A., and Wu F. C. W., Effects of testosterone on muscle strength, physical function, body composition, and quality of life in intermediate-frail and frail elderly men: a randomized, double-blind, placebo-controlled study, Journal of Clinical Endocrinology and Metabolism. (2010) 95, no. 2, 639–650, https://doi.org/10.1210/jc.2009-1251, 2-s2.0-76149135996.
10.1210/jc.2009-1251
CAS PubMed Web of Science® Google Scholar
104 Vigen R., O′Donnell C., Barón A. et al., Association of testosterone therapy with mortality, myocardial infarction, and stroke in men with low testosterone levels, The Journal of the American Medical Association. (2013) 310, no. 17, 1829–1836.
10.1001/jama.2013.280386
CAS PubMed Web of Science® Google Scholar

Citing Literature

All articles

Systematic Literature Review of the Epidemiology of Nongenetic Forms of Hypogonadism in Adult Males

Abstract

1. Introduction