| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the * Department of Urology, Case Western
Reserve University, University Hospitals of Cleveland, Cleveland VA Medical
Center, Cleveland, Ohio; and Auxilium
Pharmaceuticals, Inc, Norristown, Pennsylvania.
| Correspondence to: Allen D. Seftel, Department of Urology, Case Western Reserve University, University Hospitals of Cleveland, Cleveland VA Medical Center, 11100 Euclid Ave, Cleveland, OH 44106-5046 (e-mail: ads6{at}po.cwru.edu). |
| Received for publication March 11, 2004; accepted for publication June 12, 2004. |
 |
Abstract |
|---|
 Top Abstract Subjects and MethodsResultsDiscussionReferences |
|---|
300 ng/dL, n = 406, mean age 58 years)
reporting one or more symptoms of low testosterone were randomized to T gel
(50 mg/d and 100 mg/d), T patch, or placebo. Twenty-four–hour
pharmacokinetic profiles for T were obtained. The 3 primary end points
evaluated at 30 and 90 days posttreatment included a significant change in the
frequency of intercourse and nighttime erections per 7-day week as well as a
change in sexual desire measured on a Likert-type scale and calculated as a
mean daily score. At day 30, a significant increase from baseline in sexual
desire was noted for those on 100 mg/d T gel compared with those on 50 mg/d T
gel, T patch, or placebo (1.2 vs 0.4, 0.7, and 0.4, respectively). A
significant increase from baseline in the frequency of nighttime erections was
also noted for those on 100 mg/d T gel compared with those on 50 mg/d T gel or
placebo (51% of subjects in the 100 mg/d T gel group had an increase in
frequency vs 30% for the 50 mg/d T gel group and 26% in the placebo group).
Finally, a significant increase from baseline in the frequency of intercourse
was evidenced for those on 100 mg/d T gel compared with those on T patch or
placebo (39% of subjects in the 100 mg/d T gel group had an increase in
frequency vs 21% for the T patch group and 24% in the placebo group). Similar
results were seen for 100 mg/d T gel at day 90 for sexual desire and nighttime
erections vs placebo. These data demonstrate a clear relationship between
restoring serum T concentrations and improvement in certain parameters of
sexual function. We propose that threshold T levels are needed in order to
significantly affect improvements in sexual functioning.
Key words: Randomized controlled trial, androgen, gel, hypogonadism, sexual dysfunction
This study compared 3 active treatment regimens to a placebo regimen in a population consisting primarily of aging males with low serum T levels and the associated signs and symptoms of hypogonadism. We hypothesized that hypogonadal men with specific sexual dysfunction might receive benefit in their sexual functioning from T replacement therapy. Some results from this study have been reported previously—specifically, pharmacokinetic parameters related to serum T and dihydrotestosterone (DHT), body composition, mood, bone mineral density, and several safety parameters. In addition, significant improvements were noted relative to placebo in sexual desire, sexual performance (composite score based on the relative success of intercourse or masturbation), sexual motivation, and spontaneous erections (day or nighttime) (Steidle et al, 2003). This article focuses on the relationship between the serum T levels obtained after T supplementation and sexual desire and 2 other primary indicators of male sexual function (frequency of nighttime erections and intercourse). These 2 parameters were selected on the basis of their clear and known association with low serum T levels, as well as their diagnostic usefulness in clinical practice.
|
Subjects and Methods |
|---|
|
TopAbstractSubjects and MethodsResultsDiscussionReferences |
|---|
300 ng/dL (10.4 nmol/L) at screening (measured at a central laboratory),
and had one or more symptoms of low T (ie, fatigue, decreased muscle mass,
reduced libido, reduced sexual functioning of a nonmechanical [nonvascular]
nature) as determined by the study investigators. Except for hypogonadism, the
subjects were in generally good health.
|
The study was conducted in accordance with the Declaration of Helsinki and complied with Good Clinical Practice; all subjects signed an informed consent agreement that was previously approved by one of the study's participating institutional review boards.
Study Drugs
Topical T gel (Testim 1% [T gel]) was supplied by Auxilium Pharmaceuticals
(Norristown, Pa). The 4 daily treatments were 50 or 100 mg/d T gel, matching
placebo gel, and a transdermal T patch (Androderm, 2 patches x 12.2 mg/d
T). Approximately 5, 10, and 5 mg of the applied T dose is absorbed across
skin of average permeability during a 24-hour period for the 50 and 100 mg/d T
gel and the T patch treatments, respectively. The T gel and placebo gel were
identical and applied as 2 tubes of 50 mg/d T (100 mg/d), 1 tube of 50 mg/d T
and 1 tube of placebo (50 mg/d), or 2 tubes of placebo. Neither the subjects
nor the investigators were aware of the contents of the tubes.
All study drug treatments were applied in the morning; repeat applications occurred at the same time of day for the duration of the study. Each day in the gel-treated group, subjects applied the contents of 2 tubes. Subjects allocated to receive the T patch applied 2 adhesive patches daily. Patches were to be worn for 24 hours and then replaced each morning at approximately the same time.
Study Design
The study was designed as a randomized, multidose, multicenter, active,
placebo-controlled study. Subjects were randomized to 50 (99 subjects) or 100
mg/d (106 subjects) T gel and matching placebo gel (99 subjects) or T patch
(102 subjects). Randomization was performed to ensure an equal distribution of
treatments across study centers. The study was double-blinded for the T gel
and placebo groups and open-label for the T patch group. Subjects randomized
to 1 of the 2 T gel arms could be titrated at day 60 on the basis of their day
30 T pharmacokinetic profile. Subjects were titrated from 50 mg/d to 100 mg/d
at day 60 if their day 30 mean serum T concentration
(Cavg) was <300 ng/dL (10.4 nmol/L). Subjects were
titrated from 100 to 50 mg/d at day 60 if their day 30 T
Cavg was >1000 ng/dL (34.7 nmol/L). These titration
decisions were undertaken by a third party physician who was unaware of any
clinical aspects of the individual subjects.
Subjects had a baseline 24-hour profile for serum T consisting of serum samples taken at 8 and 10 AM and 12 and 4 PM on day -1 and 8 AM on day 1, immediately before the first dose of study drug. On days 30 and 90, subjects had another 24-hour profile for T consisting of serum samples at predose and 2, 4, 8, 12, and 24 hours after study drug administration. On day 60, a single 8 AM serum sample was taken.
Sexual function diaries were completed daily for 14 days before day 1 and daily for 7 days before days 30, 60, and 90. Data were collected centrally in real time via an interactive telephone voice response system.
Methods
Sexual functioning assessments were based on a self-report daily
diary—one that has been validated for assessment of sexual function and
mood and was used in a previous study to evaluate the effects of T gel on
sexual function (Lee et al,
2003). The diary elicited information on sexual desire and the
occurrence of nighttime erections and intercourse. Sexual desire was assessed
on a Likert-type scale (score range 0–7) and was calculated as an
average score. The evaluation of nighttime erections and intercourse was
calculated as the average number of days in a 7-day week that the events
occurred. Of note, the number of subjects evaluated for the frequency of
intercourse differs from those evaluated for sexual desire and nighttime
erections because the requirement for a steady, sexual partner was not a study
entry criterion.
Serum T levels were measured and analyzed at ICON Laboratories (Farmingdale, NY) with validated radioimmunoassay kits obtained from Diagnostic Products Corporation (Los Angeles, Calif).
Statistical Analyses
The 24-hour pharmacokinetic profiles for T were summarized by
Cavg (AUC0–24 divided by the 24-hour
sampling period, where AUC is the area under the concentration curve
calculated by the trapezoidal rule). The change from baseline to day 30 and
day 90 in T Cavg was analyzed by analysis of covariance
(ANCOVA) with the baseline value as the covariate and treatment group as the
factor.
Number of days with nighttime erections and frequency of intercourse during a 7-day week were summarized at baseline, day 30, and day 90. Change in frequency relative to baseline for intercourse and nighttime erections for day 30 and day 90 were categorized as decrease, no change, or increase and analyzed for each pair of treatments with the Mantel-Haenszel analysis of variance statistic. Change in frequency was made on the basis of the actual number of days in which a subject reported nighttime erections or intercourse in a 7-day week. The change was noted as "Decrease" if fewer days were reported during the study than during baseline; the change was noted as "No Change" if the same number of days were reported on treatment as during baseline; the change was noted as "Increase" if more days were reported during treatment than during baseline.
The change from baseline to day 30 and day 90 in mean daily score for sexual desire was analyzed by ANCOVA with baseline value as the covariate and treatment group as the factor. Subjects randomized to T gel (50 or 100 mg/d) could have their dose changed at the day 60 visit. Those subjects with a dose change were analyzed at day 90 under the dose they received at the day 60 visit. SAS version 8.02 (SAS Institute, Cary, NC) was used for all analyses. For each comparison, an alpha of .05 was considered significant. All data in tables are presented as means ± SD.
Additionally, a post hoc examination of a potential threshold relationship between sexual function response and T levels, as measured by Cavg, was carried out for each parameter. For ease of display and analysis, T levels were divided into 3 categories: below normal (0–300 ng/dL), low normal (300 to the cut-off value [CV]) and above low normal (CV+). The CV for low normal was determined separately for each sexual function parameter. We hypothesized that as T levels were restored to the therapeutic range, each sexual function parameter would demonstrate a "threshold" Cavg T value below which there was no change and above which a change occurred. Analyses similar to those involving the treatment groups were carried out with the use of the T level categorization in place of the treatment group. All pairwise category comparisons were made to highlight the threshold effect. The analysis was based on first dividing the T levels into deciles, plotting the mean values for each decile group, and then collapsing the deciles as the data indicated.
Finally, although data on sexual function response was evaluated on the basis of change in T level from baseline (rather than as the final T level vs response), no differences in correlations, significance, or interpretation were noted. Considering these results and because the actual T level vs response analysis is consistent with the threshold concept, only the actual T level vs response analysis is discussed and presented.
|
Results |
|---|
|
TopAbstractSubjects and MethodsResultsDiscussionReferences |
|---|
Sexual Desire
At baseline, the mean sexual desire scores were 2.1 ± 1.4, 2.6
± 1.4, 2.2 ± 1.3, and 2.1 ± 1.4 in the T gel 50, T gel
100, T patch, and placebo groups, respectively (score range: 0–7). A
significant increase from baseline in sexual desire was noted for the T gel
100 group (change = 1.2) compared with the T gel 50 (0.4, P <
.001), T patch (0.7, P < .0013), and placebo groups (0.4,
P < .001) on day 30; on day 90, change = 1.0 (T gel 100) vs 0.5 (T
gel 50, P = .0165), 0.6 (T patch, P = .0317), and 0.5
(placebo, P = .0035) (Figure
1). At day 30, a significant increase (P = .0269) from
baseline in sexual desire was noted for the T patch vs placebo group that was
not maintained at day 90. Mean Cavg serum T concentrations
were 213 ± 78, 377 ± 122, 346 ± 135, and 629 ± 287
ng/dL in the T gel 50, T gel 100, T patch, and placebo groups, respectively,
at day 30, and 213 ± 79, 330 ± 127, 405 ± 248, and 506
± 234 ng/dL in the same groups, respectively, at day 90
(Figure 1).
|
The change in desire correlated with the serum T levels achieved as measured by Cavg for day 30 (r = .33, P < .0001) and day 90 (r = .28, P < .0001). Similar results were seen at day 60, except that only 8 AM serum T levels were obtained for each subject, so results are therefore not reported here.
Nighttime Erections
At baseline, nighttime frequency distributions were similar across the 4
treatment groups, with 33%, 35%, 39%, and 33% in the T gel 50, T gel 100, T
patch, and placebo groups, respectively, reporting no days on which nighttime
erections occurred (Figure
2).
|
At day 30, a significant increase from baseline in the frequency of nighttime erections was noted for the T gel 100 dose compared with the T gel 50 dose (51% of subjects in the T gel 100 group had an increase in frequency vs 30% for the T gel 50 group, P = .0028) and placebo group (26%, P = .0001). At day 90, the T gel 100 group continued to demonstrate a significant increase from baseline compared with the placebo group (P = .0354) (Figure 2). At day 30, a significant (P = .0278) increase from baseline in frequency of nighttime erections was noted for the T patch vs placebo group that was not maintained at day 90.
The change in the number of days per week in which subjects reported nighttime erections was correlated with the serum T levels achieved as measured by Cavg for day 30 (r = .27, P < .0001) and day 90 (r = .28, P < .0001).
Intercourse
At baseline, intercourse frequency distributions were similar across the 4
treatment groups, with 45%, 47%, 49%, and 43% in the T gel 50, T gel 100, T
patch, and placebo groups, respectively, reporting no days on which
intercourse occurred (Figure
3).
|
At day 30, a significant increase from baseline in the frequency of intercourse was noted for the T gel 100 dose compared with the T patch and placebo groups (39% of subjects in T gel 100 dose group had an increase in frequency vs 21% in the T patch group (P = .0356) and 24% in the placebo group (P = .0096). At day 90, the T gel 100 group continued to evidence a significant increase from baseline compared with the T patch and T gel 50 groups (37% vs 13%, P = .0027, and 6% P = .001, respectively) (Figure 3). Mean Cavg serum T concentrations at day 30 for those subjects who also had a partner available were 209 ± 81, 386 ± 113, 338 ± 136, and 587 ± 216 ng/dL in the T gel 50, T gel 100, T patch, and placebo groups, respectively, and 218 ± 74, 315 ± 112, 373 ± 145, and 487 ± 213 ng/dL in the T gel 50, T gel 100, T patch, and placebo groups, respectively, at day 90 (Figure 3).
The change in the number of days per week in which subjects reported intercourse was correlated with the serum T levels achieved as measured by Cavg (r = .20, P = .0027 for day 30; r = .16, P < .0202 for day 90).
Sexual Function and Serum T Levels
We explored the possibility that there might be a threshold average daily
serum T level for sexual response, meaning a T level at which the sexual
response was no different from that of the group of subjects with the lowest
serum T level (0–300 ng/dL) and above which there was a significant
change compared with that of the group of subjects with the lowest serum T
level. This threshold level appeared to be approximately 400 ng/dL for
nighttime erections, 500 ng/dL for sexual intercourse, and 600 ng/dL for
sexual desire. In all 3 parameters, there was no significant difference in
sexual function between the group of subjects with the lowest serum T levels
(0–300 ng/dL) and the group of subjects with the next highest serum T
level (300–400 ng/dL for nighttime erections, 300–500 ng/dL for
sexual intercourse, and 300–600 ng/dL for sexual desire, P 
.16). However, there were significant differences between the group of
subjects above the threshold serum T value and the group with the lowest serum
T levels (0–300 ng/dL, P .0028). In addition, there were
significant differences between the group of subjects above the threshold
serum T value and the group of subjects with serum T levels between 300 ng/dL
and the threshold for sexual desire and intercourse (P .0098)
(Figure 4). These results
indicate that the response functions for sexual desire and intercourse were
relatively flat until the serum T levels were restored to levels above the
threshold value, whereas the response function for nighttime erections gave an
indication of an increased response even with restoration of serum T levels
into the low-normal range (300–400 ng/dL).
|
|
Discussion |
|---|
|
TopAbstractSubjects and MethodsResultsDiscussionReferences |
|---|
Signs and symptoms of low T in adult males include loss of libido and erectile dysfunction (Tenover, 1998; Petak et al, 2002). Men affected by this condition report irritability, loss of concentration, declining libido, erectile dysfunction, and a decreased sense of well-being (Tenover, 1998). Mood disorders such as depression and behavioral symptoms such as irritability and lethargy also occur. Some regression of secondary sexual characteristics such as reduced auxiliary and pubic hair might be observed, but voice, penis length, and prostate size often remain unchanged (Braunstein 1997; Tenover, 1998; Petak et al, 2002).
How does testosterone affect sexual function? In hypogonadal men, spontaneous erections have been shown to be androgen dependent (Davidson et al, 1979; Shakkebaek et al, 1981; O'Carroll et al, 1985) and erections in response to erotic stimuli have been shown to be androgen independent (Bancroft and Wu, 1983; Kwan et al, 1983). In terms of the relationship between mood and androgens, several studies have demonstrated a positive effect (O'Carroll et al, 1985; Wang et al, 1996b; Anderson et al, 1999; Wang et al, 2000), whereas other studies have not (Davidson et al, 1979). Thus, many relationships between hypogonadism and sexual function have not been fully elucidated. This placebo-controlled study attempts to address these deficient areas. The study reported here includes comparisons among 4 parallel treatment groups in a population of aging, hypogonadal men reporting at least one or more symptoms of hypogonadism, with a specific focus on desire and erectile function reported in this data set. Active treatments consisted of either 50 or 100 mg/d T gel or a T patch (2 patches, each delivering 2.5 mg/d T), doses that have been shown to produce clinically relevant increases in serum T levels (Dobs et al, 1999). A fourth group of matching placebo gel was also included to provide a valid and definitive assessment of clinical and subjective symptom improvements. The sexual function response was based on daily logs, which were part of a self-report diary that had been used previously in the development of other T preparations (Wang et al, 1996; Swerdloff et al, 2000).
Sexual desire increased in all treatment groups, including the placebo group, confirming the partially subjective nature of the entity termed "desire." Because of the notable placebo effect, the data suggest that average daily serum T levels need to be in excess of a threshold of 600 ng/dL in order to detect a significant treatment effect over and above the placebo effect.
Intercourse was recorded daily for 14 days before the end of the baseline period and daily for 7 days before the end of the first, second, and third 30-day treatment periods; hence, the total occurrences of intercourse during a 30-day period was not captured as were other measurement instruments based on a 1-month recall methodology. Notwithstanding this methodological difference, a clear treatment effect of T gel 100 was seen at day 30 compared with T gel 50, T patch, and placebo. At day 90, there were still no differences seen among the T gel 50, T patch, and placebo groups. However, the T gel 100 group was significantly different from T patch and T gel 50 and marginally significantly different from the placebo group (P = .06) at day 90. Because subjects were included in this analysis only if they had a partner available at least 4 days out of each questionnaire period, there were fewer subjects in this analysis, resulting in some loss of power. A sexual partner was not mandatory for entry into this study; however, approximately 80% of all men had a partner available. Even though there were fewer subjects, it still followed that the percentage of subjects who experienced an increase in frequency of intercourse was significantly higher in those subjects whose average daily serum T levels were above 500 ng/dL than in those whose serum T levels were less than 500 ng/dL, regardless of how much less.
Nighttime erections occurred at a higher rate in the T gel 100 compared with the placebo group at both day 30 and day 90. The increase in nighttime erections seemed to start at a lower average daily serum T level than seen in the other 2 sexual parameters (400 ng/dL), suggesting that this androgenic effect is among the first to be restored or affected as the serum T levels are raised with T replacement therapy
Notwithstanding the fact that this study was not designed to measure explicitly a threshold effect, especially whether the threshold is strongly subject dependent, these exploratory analyses demonstrated a clear relationship between the restoration of T levels and significant improvements in basic aspects of sexual function (eg, sexual desire, frequency of nighttime erections, and frequency of intercourse). The results also indicate that there might be threshold serum T levels associated with improvements in sexual function that are higher than the levels required to affect changes in other areas negatively affected by the hypogonadal state (eg, body composition) and that additional studies should be conducted to further investigate this correlation. Furthermore, these findings are consistent with studies conducted in eugonadal young men in which hypogonadism was induced with a GnRH antagonist.
The data from this study demonstrate that T replacement in hypogonadal men has an effect on sexual desire, frequency of nocturnal erections, and frequency of sexual intercourse. The novel concept explored herein—specifically, that a threshold value exists above which a demonstrable effect is evidenced—provides further guidance to clinicians regarding T replacement therapy.
|
Footnotes |
|---|
|
References |
|---|
|
TopAbstractSubjects and MethodsResultsDiscussionReferences |
|---|
Arver S, Dobs AS, Meikle AW, Allen RP, Sanders SW, Mazer NA. Improvement of sexual function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system. J Urol. 1996;155: 1604 -1608.[Medline]
Bagatell CJ, Heiman JR, Rivier JE, Bremner WJ. Effects of endogenous testosterone and estradiol on sexual behavior in normal young men. J Clin Endocrinol Metab. 1994; 78: 711 -716.[Abstract]
Bancroft J, Wu FC. Changes in erectile responsiveness during androgen replacement therapy. Arch Sex Behav. 1983; 12: 59 -66.[Medline]
Bhasin S, Woodhouse L, Casaburi R, et al. Testosterone
dose-response relationships in healthy young men. Am J Physiol
Endocrinol Metab. 2001;281: E1172
-E1181.
Braunstein GD. Testes. In: Greenspan FS, Strewler GJ, eds. Basic and Clinical Endocrinology. 5th ed. Stamford, Conn: Appleton & Lange; 1997: 403 -433.
Buena F, Swerdloff RS, Steiner BS, Lutchmansingh P, Peterson MA, Pandian MR, Galmarini M, Bhasin S. Sexual function does not change when serum testosterone levels are pharmacologically varied within the normal male range. Fertil Steril. 1993; 59: 1118 -1123.[Medline]
Burris AS, Banks SM, Carter CS, Davidson JM, Sherins RJ. A
long-term, prospective study of the physiologic and behavioral effects of
hormone replacement in untreated hypogonadal men. J
Androl. 1992;13: 297
-304.
Davidson JM, Camargo CA, Smith ER. Effects of androgen on sexual behavior in hypogonadal men. J Clin Endocrinol Metab. 1979; 48: 955 -958.[Abstract]
Dobs AS, Meikle AW, Arver S, Sanders SW, Caramelli KE, Mazer NA.
Pharmacokinetics, efficacy, and safety of a permeation-enhanced testosterone
transdermal system in comparison to bi-weekly injections of testosterone
enanthate for the treatment of hypogonadal men. J Clin Endocrinol
Metab. 1999;84: 3469
-3478.
Fielder TJ, Peacock NR, McGivern RF, Swerdloff RS, Bhasin S.
Testosterone dose-dependency of sexual and nonsexual behaviors in the
gonadotropin-releasing hormone antagonist-treated male rat. J
Androl. 1989;10: 167
-173.
Kwan M, Greenleaf WJ, Mann J, Crapo L, Davidson JM. The nature of androgen action on male sexuality: a combined laboratory-self-report study on hypogonadal men. J Clin Endocrinol Metab. 1983; 57: 557 -562.[Abstract]
Lee KK, Berman N, Alexander GM, Hull L, Swerdloff RS, Wang C. A
simple self-report diary for assessing psychosexual function in hypogonadal
men. J Androl. 2003; 24: 688
-698.
Liverman CT, Blazer DG, eds. Testosterone and Aging: Clinical Research Directions. Washington, DC: The National Academies Press; 2004.
O'Carroll R, Shapiro C, Bancroft J. Androgens, behavior and nocturnal erection in hypogonadal men: the effects of varying the replacement dose. Clin Endocrinol (Oxf). 1985; 23: 527 -538.[Medline]
Petak SM, Nankin HR, Spark RF, Swerdloff RS, Rodriguez-Rigau LJ (for the AACE Hypogonadism Task Force). American Association of Clinical Endocrinologists medical guidelines for clinical practice for the evaluation and treatment of low testosterone in adult male patients—2002 update. Endocr Pract. 2002; 8: 439 -456.
Skakkebaek NE, Bancroft J, Davidson DW, Warner P. Androgen replacement with oral testosterone undecanoate in hypogonadal men: a double blind controlled study. Clin Endocrinol (Oxf). 1981; 14: 49 -61.[Medline]
Steidle C, Schwartz S, Jacoby K, Sebree T, Smith T, Bachand R.
AA2500 testosterone gel normalizes androgen levels in aging males with
improvements in body composition and sexual function. J Clin
Endocrinol Metab. 2003;88: 2673
-2681.
Swerdloff RS, Wang C, Cunningham G, et al. The Testosterone Gel
Study Group. Long-term pharmacokinetics of transdermal testosterone gel in
hypogonadal men. J Clin Endocrinol Metab. 2000; 85: 4500
-4510.
Tenover JL. Male hormone replacement therapy including "andropause." Endocrinol Metab Clin North Am. 1998;27: 969 -987.[Medline]
Wang C, Alexander G, Berman N, et al. Testosterone replacement therapy improves mood in hypogonadal men—a clinical research center study. J Clin Endocrinol Metab. 1996a; 81: 3578 -3583.[Abstract]
Wang C, Swerdloff RS, Iranmanesh A, et al. Transdermal testosterone
gel improves sexual function, mood, muscle strength, and body composition
parameters in hypogonadal men. J Clin Endocrinol
Metab. 2000;85: 2839
-2853.
This article has been cited by other articles:
|
|
 |
|
  M. Wald, M. Miner, and A. D. Seftel State of the Art Reviews: Male Menopause: Fact or Fiction? American Journal of Lifestyle Medicine, April 1, 2008; 2(2): 132 - 141. [Abstract] [PDF]
|
|
|
|
 |
|
 T. G. Travison, J. E. Morley, A. B. Araujo, A. B. O'Donnell, and J. B. McKinlay The Relationship between Libido and Testosterone Levels in Aging Men J. Clin. Endocrinol. Metab., July 1, 2006; 91(7): 2509 - 2513. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Bhasin, G. R. Cunningham, F. J. Hayes, A. M. Matsumoto, P. J. Snyder, R. S. Swerdloff, and V. M. Montori Testosterone Therapy in Adult Men with Androgen Deficiency Syndromes: An Endocrine Society Clinical Practice Guideline J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 1995 - 2010. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
