DIFFERENTIAL TESTOSTERONE DEFICIENCY IN HYPOGONADAL MEN WITH ED

MAMDOUH MOHAMED * AND ALLEN D. SEFTEL.**

*Minia University Hospital, Minia Egypt.and **Dept of Urology Case western Reserve University, University hospiital Of Cleveland, Cleveland OH.
 

Aim of the study: The primary study end-point of this study was the determination of the prevalence of different types of serum testosterone deficiency in men presented for office evaluation of ED and low libido.

Patients and Methods: To determine the prevalence of differrent testosterone deficiency in men presented for office evaluation of their erectile dysfunction[ ED] ,total,free and % free serum testosterone levels were obtained from 69 patients presenting to out patients urology clinics at Urology Dept. Minia Uinversity Hospital Mini Egypt with a chief complaint of ED in the period between June 2008 and May 2010. Samples were drawn between 8-11 Hs in all patients. All men in this study had ED and low sex drive (libido), several validated questionnaires (SHIM and ADAM) were I filled in the office prior to the examination. Sixty nine men were included in this study with average age 63 (mean 56 ± 12) were evaluated over a 12 month period met criteria for inclusion. The patients completed these questionnaires in the office, prior to physician interview. All men had serum testosterone levels drawn. [total, free and % free testosterone]. Hypogonadism, defined as total serum T<300 mg/dl, free T<2.5 ng/dl or r < 4.50 ng /dl depending on the laboratory kits), and %free T <0.62ng/dl or < 4ng/dl).

Results: All 69 men had ED, with an average SHIM score of 11+, Low serum testosterone level (Hypogonadism) was seen in 28 patients out of 69 patients (40.57%); of those 28 men ,13 patients had low total testosterone (18.45%), 17 patients had low free testosterone (24.63%), and 11 patients had low % free testosterone level (15.94%). 6. While low libido was noted in 97% of men using ADAM questionnaire for the detection of men with low sex drive.

Conclusion: These data support the concept that male erectile dysfunction now must be considered in the office evaluation of male erectile dysfunction, all types of serum testosterone either total, free and % free shoud be put in mind for diagnosis of men with ED and low libido.

 

INTRODUCTION

In 2004 Rhoden and Morgentaler defined hypogonadism as a total serum testosterone (T) levels less than 300 ng/dl associated with one or more clinical symptoms or sign. Symptoms of postpubertal hypogonadism include sexual dysfunction, such as decreased libido, erectile dysfunction (ED), diminished penile sensation, difficulty attaining orgasm, in addition to reduced volume of ejaculate during orgasm; reduced energy, vitality, or stamina; depressed mood or diminished sense of well-being increased irritability, difficulty concentrating and other cognitive problems; and/or hot flushes in some cases of acute onset.

 

In 1998 Laumann and Shabsigh stated that office evaluation of male sexual dysfunction (ED) has extended to include areas of low sex drive, depression and premature ejaculation, together with an office evaluation of erectile dysfunction. These new concepts are based on the National Health and Social Life Survey (The management of male erectile dysfunction (ED) historically was in the domain of the urologist. It is important to recognize the coexistence, of these conditions because, first, it may change the scenario of treatments of men with ED, and second, clinical diagnosis of men with low sex drive and their treatment may lead to a significant improvement in quality of life of those men. Increasing evidence indicates that low testosterone Levels are associated with cardiovascular disease as well as diabetes.

 

In 1988 Kaiser stated that decrease in serum testosterone levels in men with erectile dysfunction (ED) remains unclear. In 2002 Rhoden mentioned that despite both hypogonadism and ED increase with age, serum testosterone levels are the same levels in men with ED and in those without erectile dysfunction, and levels can be similar among patients with different severities of erectile dysfunction. These data suggest that ED and hypogonadism may be independent. However, it is possible that a certain threshold level of testosterone is required for full sexual function, and that assessments of mean values may obscure the importance of testosterone in ED.

 

The available of oral therapy nowadays allowed the primary care physician to diagnose and treat men with hypogonadism and male sexual dysfunction. Confounding the issue of male ED was data that demonstrated that male ED was part of a larger sexual dysfunction model, this new model incorporated areas of premature ejaculation, ED, depression and low sex drive. Old aged men have more ED and lower serum testosterone, but the two issues are not necessary causally related. The age-related variation in the prevalence of ED is well -known from the Massachusetts Male Aging Studies.

 

PATIENTS AND METHODS

To determine the prevalence of the three different types of testosterone deficiencies (Hypogonadism), in men presented with low libido and erectile dysfunction, several validated questionnaires (SHIM and ADAM questionnaire) were applied into the office evaluation of men with ED, Sixty nine men with age 63 (mean 56±12) evaluated over a 12 month period met criteria for inclusion. All men completed these questionnaires in the office, prior to physician examination. All men had serum testosterone levels drawn for total, free and % free testosterone measurments. The primary study end-point was the determination of the prevalence of different types of testosterone defeciency, low libido and ED. The Sexual Health Inventory for Men (SHIM) questionnaire is designed to have 5 questions that best describe Ed patients, each question has several possible response from 1-5.This questionnaire was completed by the patient in the waiting room just before the examination. The SHIM score was appended and scored as follow. Score 22-25 no ED, score 17-21.mild ED, score 12-16. mild to moderate ED, score 8-11 moderate ED, score 0-7. severe ED (!! psychogenic). A copy of ADAM (Androgen Defeciency of Aging Men) questionnaire was applied for each men, we considered patient as positive for ADAM questionnaire if he answered yes response to the question no 1 and No response to question no 7, or yes response to any other three questions., Serum testosterone levels total, free and % free testosterone levels were done for all patients in this sereis using single dated sample to measure the testosterone levels in all patients, we considered.

Low total testosterone level if the total testosterone level is < 300 ng/ml, low free testosterone levels if free testosterone < 2.5 ng/dl or < 4.50 ng /dl in and low % free testosterone levels if % free testosterone < 0.62ng/dl in or < 4ng/dl depending on the different laboratory results and according to laboratory kits available.

RESULTS

This prospective study was carried out upon sexily nine men all were presented to office evolution for their erectile quality and all had ED, with an average SHIM score of 11+6, low sex drive (answering no for question 7 in the ADAM questionnaire) was the main presenting symptoms in 58 patients out of 69 (97%), SHIM score was positive in 58 out of 69 patients and negative only on 2 cases see figure (1). 

Nine patients were missed for SHIM questionnaire, SHIM scores was positive in 26 patients who have low testosterone levels (28); the remaining two patients were missed. Correlation of SHIM score with the degree of ED, erectile dysfunction was mild in 11 patients (18.3%), mild to moderate in 12 patients (20%), moderate in 16 patients (26.6%)and severe in 19 cases (31.6%) see table 1.

As regards to ADAM questionnaire, it was positive in 67 patients from the total 69, 58 patients answer no for question 7 and 46 patients answer yes for question 1 an yes. Answer yes for other three questions. Low serum testosterone level (Hypogonadism) was seen in 28 patients out of 69 patients (40.57%); of those 13 patients have low total testosterone (18.45%), 17 patients have low free testosterone (24.63%), and 11 patients have low % free testosterone level (15.94%). In patients with low total testosterone only one patient has low % free testosterone, and 6 patients have low free testosterone level see table 2, Free and % free testosterone in low total testosterone patients (13 patients).

[image]

Figure (1): Shows degree of ED using SHIM score in all patients in this series.


[image]

Figure (2): Shows types of testosterone deficiency in 28 with hypogonadism

 

Table (1): Show incidence of low free and % free testosterone in 13 patients with low total testosterone]

Low total testosterone

free testosterone

% free testosterone

286

2.46l

0.86

208

3.26

1.57

200

3.78

1.39

200

3.78l

1.39

201

0.288l

1.43

225

3.12

1.56

252

3.42

1.38

183

3.73l

2.04

189

1.85l

0.98l

220

2.99

1.36

236

2.96

1.5

290

3.84 l

1.2

166

Missed

1.2

 


Table (2):
Shows low both % free testosterone and total testosterone in patients with low free testosterone

FREE

Testosterone level

(Low if < 2.5 ng/dl or < 4.50 ng /dl )

% FREE

Testosterone level

(Low <0.62ng/dl or < 4ng/dl .)

TOTAL

Testosterone level

(Low if < 300 ng /ml)

2.46

1.9l

464

2.46

0.86

286l

4.22

1.27

331

0.88

0.28

311

3.78

0.39

200l

1.72

0.40

429

0.288

1.43

201

4.36

2.4

381

2.25

0.39l

584

4.11

1.7

313

3.73

2.04

183

1.85

0.98

189

1.93

0.28l

676

4.43

1.38

323

3.48

1.2

290

3.3

0.96

344

4.25

0.83

513

 

 

Table (3): Shows prevalence of hypogonadism among patients with low sexual drive

Testosterone deficiency

No

% of hypogonadism in ED patients with low libido

Total testosterone

13 /69

19 %

Free T

17 / 64

27 %

% Free

11 / 66

17 %

Total numbers of hypogonadal men

26 /69

37.7 %

 [image]

Figure (3): Shows prevalence of hypogonadism in men with low libido


Low free testosterone levels was seen in 17 patients out of 69 patients, of those 8 patients have also low % free testosterone and 6 patients have low total testosterone were see table three.

In the 11 patients with low % free testosterone only 2 have low free testosterone and 3 have low total testosterone levels

 

DISCUSSION

In the recent era of sexual dysfunction nowadays the paradigm of male erectile dysfunction must be extended to include the four major components of sexual dysfunction, including premature ejaculation, erectile dysfunction, low sex drive and depression.

 

In 1988 Kaiser strongly suggested that, in animal systems, testosterone has direct effects on erectile tissue. However, although testosterone clearly has an impact on libido in humans, its effect on physiological process of erection is less clear. For men with low sex drive and/or hypogonadism, treatment with testosterone in those patients may also improve their erectile quality or ED this statement was published by Schultheiss in 2000. These new areas were based on the National Health and Social Life Survey by Laumann in 1999 and by Shabsigh in 1998. Increasing evidence indicates that low serum testosterone levels are associated with cardiovascular disease and/or DM. Early clinical trials have shown that testosterone replacement therapy can decrease some individual cardiovascular risk factors, which include visceral obesity, insulin resistance, hypercholesterolaemia, and inflammatory markers. Meanwhile, studies animal studies have demonstrated beneficial effects of testosterone on atherogenesis. Shores in 2006 reported the importance of these findings by a study of 858 men that found increased mortality in men (male veterans) who had a low testosterone levels at baseline. This is supported by data from the Massachusetts Male Aging Study (MMAS), which found that a low total testosterone level almost doubled the risk of all-cause mortality [Araujo AB, 2005]. Low testosterone is associated with low libido. Morley in. 2000 describes the Androgen Deficiency in Aging Men or ADAM questionnaire, which is relatively easy to administer and to use. Laumann et al have (1999) demonstrated that low libido and ED were comparable in prevalence in his recent publication.

 

In this prospective study we found that ADAM questionnaire is positive in 67 patients from the total 69 [97.1%]. In our series of 69 men we found that hypogonadism present [Low serum testosterone level] in 28 patients out of 69 patients (40.57%); of those hypogonadal men, 13 had low total testosterone (18.45%), 17 had low free testosterone (24.63%), and 11 patients had low % free testosterone level (15.94%). The positive effects of T on mood and sexual behavior in hypogonadal men are well established (RA, Bancroft J, Wu FCW 1992).

 

However, less research has investigated the influence of exogenous T on sexual behavior in eugonadal men [Alexander GM, et al 1997]. Total testosterone (T) decreases at the rate of 0.11 nmol/L (3.2 ng/dL) per year (Harman et al, 2001). Both the total and the free testosterone decline with aging. A fixed lower reference limit of testosterone, 10.4 nmol/L (300ng/dL), is used in most studies. In 1999 Basaria and Dobs, 1999 confirmed the loss of the circadian rhythm of testosterone secretion with aging The prevalence of hypogonadism is estimated to be 20% for men 65 years and older (Feldman et al, 1994) and may be as high as 92% for men older than 80 years if the free testosterone is used as the diagnostic test (Harman et al, 2001). The significance of this hypogonadism is hotly debated, with many health care professionals treating older men to attain serum testosterone levels similar to those of a middle-aged man (mean serum total T in a 40-year-old man is 500 ng/dL), whereas other health care professionals propose that age-adjusted values should be used to estimate the prevalence of hypogonadism (Schatzl et al, 2003).

 

CONCLUSION

so our conclusions in this prospective study is that, Low serum testosterone levels assume an increasingly important role in the office evaluation of male sexual function, measurements of three types of tesetosterone must be done and diagnosis of hypogonadism shoud be considered if any one of these is low. ADAM questionnaire is sensitive, but not specific for diagnosis of men with hypogonadism.
 

REFERENCES

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