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Original Articles: Hormones and Reproductive Health |
Divisions of Endocrinology, Metabolism, and Molecular Medicine (A.B.S., I.S.-H., R.S., T.D., S.B.) and Nephrology and Hypertension (K.N.), Charles R. Drew University of Medicine and Science, Los Angeles, California 90059; and Alza Corporation (N.M.), Mountain View, California 94043
Address correspondence and requests for reprints to: Shalender Bhasin, M.D., Professor of Medicine, UCLA School of Medicine, Chief, Division of Endocrinology, Metabolism, and Molecular Medicine, Charles R. Drew University of Medicine and Science, 1731 East 120th Street, Los Angeles, California 90059.
Abstract
Androgen deficiency is common in men with end stage renal disease (ESRD) on maintenance hemodialysis. Pharmacokinetics of transdermal testosterone in men receiving maintenance hemodialysis have not been studied.
Our objective was to compare the pharmacokinetics of a transdermal testosterone system in healthy hypogonadal men and in men with ESRD on maintenance hemodialysis.
We recruited 10 healthy hypogonadal men and 8 medically stable men on maintenance hemodialysis, 18–70 yr old, who had serum testosterone less than 300 ng/dL. After baseline sampling during a 24-h control period, two testosterone patches were applied daily for 28 days, to achieve a nominal delivery of 10-mg testosterone daily. In addition to single, pooled samples on days 7, 14, and 21, blood was drawn at 0, 2, 4, 6, 8, and 24 h on day 28 in healthy hypogonadal men and on an interdialytic day (day 21 or 28) as well as a dialysis day (day 21 or 28) in men on hemodialysis. On the dialysis day (day 21 or 28), serum free and total testosterone levels were measured hourly for 4 h before hemodialysis and for 4 h during hemodialysis. The dialysate was sampled for testosterone measurement.
Baseline mean + SD total (92 ± 82 vs. 222 ± 50 ng/dL) and free (11 ± 9 vs. 27 ± 6 pg/mL) testosterone concentrations were lower in healthy hypogonadal men than in men with ESRD. After application of two testosterone patches, serum total and free testosterone concentrations rose into the midnormal range in both groups of men. Time-average, steady state (total testosterone, 506 ± 88 vs. 516 ± 86 ng/dL; free testosterone, 55 ± 9 vs. 67 ± 11 pg/mL), minimum, and maximum total and free testosterone concentrations were not significantly different between the two groups of men during treatment. Increments in total and free testosterone concentrations above baseline, baseline-subtracted areas under the total and free testosterone curves, and half-life of testosterone elimination (t1/2, 2.1 ± 0.1 vs. 2.1 ± 0.2 h, P = not significant) were not significantly different between the two groups. In men receiving hemodialysis, time-average, steady state, and maximal total and free testosterone concentrations and baseline-subtracted areas under the total and free testosterone curves were higher on dialysis day than on an interdialytic day. On the day of hemodialysis, time-average total and free testosterone concentrations were not significantly different during the 4 h before or during hemodialysis. The amount of testosterone removed in the dialysate (8.4 ± 1.6 µg during 4 h of hemodialysis) was small compared with the daily testosterone production rates in healthy young men. Serum dihydrotestosterone and estradiol concentrations increased into the normal male range and were not significantly different between the two groups. Percent suppression of LH was greater in men with ESRD than in healthy hypogonadal men.
A regimen of two Testoderm TTS testosterone patches (Alza Corp., Mountain View, CA) daily can maintain serum concentrations of total and free testosterone and its metabolites dihydrotestosterone and estradiol in the midnormal range in healthy hypogonadal men and men on hemodialysis. The amount of testosterone cleared by hemodialysis is small, and hemodialysis does not significantly affect serum total and free testosterone concentrations in men treated with the testosterone patch.
TWO HUNDRED FIFTY thousand patients with end stage renal disease (ESRD) in the United States receive maintenance hemodialysis, and this patient population has been steadily increasing. Two thirds of men on hemodialysis have serum testosterone levels in the hypogonadal range (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12). Androgen deficiency in men with ESRD results from abnormalities at all levels of the hypothalamic-pituitarytesticular axis (1, 2, 13, 14, 15, 16, 17, 18, 19, 20). There is a high prevalence of infertility, gynecomastia, and sexual dysfunction in men on hemodialysis (1, 2, 9, 21). Malnutrition and reduced muscle mass (sarcopenia) are common in these patients and correlate with increased mortality and adverse disease outcomes (22, 23, 24, 25, 26, 27, 28). Decreased muscle mass and strength contribute to impaired physical function; therefore, it is not surprising that approximately one third of men receiving hemodialysis need assistance with activities of daily life (29, 30). Sarcopenia observed in association with hemodialysis and other chronic illnesses is a multifactorial process resulting from multiple metabolic perturbations, decreased physical activity, chronic illness, and abnormalities in the cardiovascular, hematological, and neuromuscular systems. One correctable cause of the decrease in muscle mass and strength that occurs in men on hemodialysis is the decrease in serum testosterone concentrations (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20). Therefore, there is considerable interest in determining whether testosterone replacement of men on maintenance hemodialysis who have low testosterone levels will increase their fat-free mass, muscle strength, physical function, and health-related quality of life. However, there is a paucity of data on the pharmacokinetics of testosterone in men on hemodialysis. Although testosterone is cleared by dialysis, it is not known what effect hemodialysis might have on the overall clearance and plasma concentrations of testosterone in men on hemodialysis (31, 32, 33).
The objective of this study was to determine the pharmacokinetics of a testosterone transdermal formulation in men on hemodialysis and ascertain whether a regimen of two testosterone patches applied daily can achieve in these men serum total and free testosterone concentrations in the range that is midnormal for healthy young men. A single testosterone transdermal system that achieves a nominal delivery of 5 mg testosterone over the 24-h application period increases serum testosterone concentrations into the low to midnormal male range in healthy, hypogonadal men (34, 35). Because we wanted to raise serum testosterone concentrations consistently in to the midnormal range, we used a regimen of two testosterone patches daily (nominal delivery 10 mg/day). As a reference for comparison, we concurrently studied a group of healthy hypogonadal men with normal renal function who were treated with a similar regimen. To determine the effects of hemodialysis on plasma total and free testosterone concentrations, we performed detailed 24-h sampling both on a hemodialysis day and an interdialytic day. We also measured the amount of testosterone removed during hemodialysis.
Materials and Methods
All subjects gave written informed consent, and the Institutional Review Board of the Charles R. Drew University of Medicine and Science approved the study.
Participants
Healthy hypogonadal men. We recruited 10 healthy hypogonadal men, 18–70 yr of age, between 90–120% of their ideal body weight, who had normal blood urea nitrogen, creatinine, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and albumin levels. The participants had baseline serum testosterone levels less than 300 ng/dL, the lower limit of the normal range for healthy young men. Men with multiple pituitary hormone deficiencies were eligible if they had been on stable thyroid and glucocorticoid replacement therapy for at least 3 months. Those who had been receiving testosterone replacement therapy were asked to discontinue testosterone at least 6 weeks before entry into this study.
Men with ESRD on maintenance hemodialysis. Eight men with ESRD, 18–70 yr of age, who were clinically stable, had baseline testosterone levels less than 300 ng/dL, and normal liver enzymes were recruited for this study. We excluded men with diabetes mellitus and human immunodeficiency virus infection. Patients who were receiving medications that affect testosterone production and action or sex hormone-binding globulin (SHBG) levels were also excluded.
Testosterone transdermal system. Testosterone transdermal system (Testoderm TTS; Alza Corp., Mountain View, CA) is a 60-cm2 system that contains 328 mg testosterone and is designed to achieve a nominal delivery of 5 mg testosterone over the 24-h application period (34, 35). The 5-mg testosterone patch, when applied daily, raises serum testosterone concentrations in healthy hypogonadal men into the low to midnormal range (34, 35). In this study, each subject applied two patches daily on the upper buttocks to nominally deliver 10 mg testosterone daily.
Study protocol. Any previous testosterone therapy was discontinued 6 weeks before entry in this study. The study consisted of a screening period, a 24-h control period, and a 28-day treatment period.
Screening A medical history was obtained, and physical examination was performed. Blood was drawn for complete blood counts, chemistries, prostate-specific antigen (PSA), and serum total testosterone levels to determine eligibility. All medications were recorded.
Control period On a nondialysis, control day (day 0) when no transdermal system was applied, baseline blood was drawn at 0, 1, 2, 4, 6, 8, and 24 h, in the Clinical Research Center, starting between 0800 and 0900 h. Blood counts, chemistries, and serum lipid and hormone concentrations were measured.
Treatment period After 24 h of baseline sampling, the patients applied daily two Testoderm TTS patches on the upper aspect of each buttock. Patients were taught how to apply the patches, instructed to change the patches every morning after shower, and were given a 7-day supply. On treatment days 7 and 14, the participants returned to the clinical study center. Any adverse effects were recorded, blood was drawn for hormone measurements, and the used patches were counted to verify compliance.
In healthy hypogonadal men on day 28, blood samples were drawn at 0, 1, 2, 4, 6, 8, and 24 h after patch application. After obtaining the 24-h blood sample, the patches were removed and blood was taken at 15, 30, 60, 90, 120, and 150 min.
The men with ESRD underwent detailed sampling on days 21 and 28; one of these days was randomly selected to be a dialysis day. Thus, the dialysis day was day 21 in some subjects and day 28 in others. On the interdialytic day (day 21 or 28), blood samples were drawn at 0, 1, 2, 4, 6, 8, and 24 h after patch application. After obtaining the 24-h blood sample, the patches were removed and blood was taken at 15, 30, 60, 90, 120, and 150 min.
On the dialysis day (day 21 or 28), an early morning baseline sample was obtained, old patches were removed, and two new patches were applied 4 h before dialysis. After application of patches, blood was drawn at 1, 2, 3, and 4 h, and dialysis was commenced at the end of the fourth hour. Additional blood samples were obtained at 5, 6, 7, and 8 h, while the patient was on dialysis. The volume of dialysate was recorded, and several aliquots of dialysate were collected from the exit port of dialysis machine for testosterone measurement. After obtaining the 24-h blood sample, the patches were removed and blood was taken at 15, 30, 60, 90, 120, and 150 min.
Evaluation procedures and outcome measures. The primary outcome measures were serum total and free testosterone levels. We also measured serum dihydrotestosterone (DHT), LH and FSH, 17ß-estradiol, and SHBG levels on days 7, 21, and 28. Hemoglobin, hematocrit, PSA, plasma lipids, and liver enzymes were monitored as safety parameters.
Hormone measurements. Serum total testosterone levels were measured by using a RIA that uses iodinated testosterone as tracer (36, 37, 38). This assay has a sensitivity of 0.44 ng/dL and intra- and interassay coefficients of variation of 13.2 and 8.2%, respectively.
Free testosterone levels were measured by a sensitive equilibrium dialysis method (39, 40), optimized to measure low concentrations with precision and accuracy. Two hundred microliters of serum in the inner compartment were dialyzed against 2.4 mL dialysis buffer that approximates the composition of a protein-free ultrafiltrate of human serum (8). Dialysis was performed overnight for 16 h at 37 C. Testosterone concentration in the dialysate was measured by a RIA (8), using 125I-labeled testosterone. The sensitivity of the free testosterone assay was 0.6 pg/mL (2.0 pmol/L), and the intra- and interassay coefficients of variation were 4.2 and 12.3%, respectively. Serum LH, FSH, and SHBG levels were measured by two-site-directed, immunofluorometric assays (Delfia-Wallac, Inc. Gaithersburg, MD), with sensitivities of 0.05 U/L, 0.15 U/L, and 6.25 nmol/L, respectively, as described previously (37, 38). The intra- and interassay coefficients of variation were 10.7% and 13.0% for LH, 3.2% and 11.3% for FSH, and 10.0% and 10.2% for SHBG, respectively. For measurements of serum DHT levels, serum was extracted with a mixture of ethyl acetate and hexane before celite chromatography (38). The fractions containing DHT were taken up in assay buffer and assayed in a RIA using iodinated DHT as tracer. The cross-reactivity of testosterone, estradiol, androstenedione, and dehydroepiandrosterone in this assay were less than 1%, the assay sensitivity was 2.5 ng/dL, and the intra- and interassay coefficients of variation were 7.3% and 14.6%, respectively.
Calculation of the amount of testosterone removed by hemodialysis. We recorded the flow rate and the total volume of the dialysate over 4 h of hemodialysis. Aliquots of the dialysate were collected at the end of the first and fourth hour of dialysis. Testosterone was extracted from 20 mL dialysate by using ethyl acetate and hexane (39) and reconstituted in 0.5 mL assay buffer before testosterone assay.
Pharmacokinetic modeling. Baseline and pharmacokinetic parameters were averaged across subjects within each group to obtain means, SD, and SEM. The bioavailability of testosterone was described as area under the testosterone curve (AUC). The time-average free and total testosterone concentrations during the 24-h control period (baseline levels) were computed from the areas under the respective curves, divided by 24 h. We evaluated the following pharmacokinetic parameters from the 24-h profiles of free and total testosterone measured on day 28 in healthy hypogonadal men, and on dialytic and interdialytic days in men receiving maintenance hemodialysis: time-average, steady state concentration (Css), maximum concentration (Cmax), minimum concentration (Cmin), increment in time-average concentration above baseline (C’ss), increment from time time-average baseline concentration to maximum concentration (T-increment max), time of maximum concentration (Tmax), AUC, and baseline-subtracted AUC (AUC’). The Css and C’ss parameters were computed from AUC and AUC’, respectively, by dividing by 24 h.
Half-life (t1/2) of total and free testosterone was calculated from the exponential decay of serum total and free testosterone concentrations after the removal of the patch at 24-h. Half-life (t1/2) was calculated as 0.693/k where k is elimination rate of the drug.
Statistical analysis. The hormone concentrations and pharmacokinetic parameters in men on hemodialysis on an interdialytic day, and healthy hypogonadal men were compared using two-tailed, unpaired t tests. P values of less than 0.05 were considered statistically significant. Similarly, in men on hemodialysis, the AUCs and hormone concentrations on dialytic and interdialytic days were compared using paired t test.
Results
Baseline characteristics of participants (Table 1
). Ten healthy hypogonadal men and
eight men on hemodialysis completed 28 days of treatment. One man on
hemodialysis did not have his patches on the interdialytic sampling
day; therefore, the total and free testosterone data on this day are
derived from seven men.
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). Healthy
hypogonadal men were younger and had lower mean (SD) serum
testosterone levels at baseline (Table 1). Seven of 10 healthy
hypogonadal men had secondary hypogonadism: 6 had idiopathic
hypogonadotropic hypogondism, and 1 had developed androgen deficiency
following resection of a pituitary adenoma. Three healthy hypogonadal
men had primary testicular dysfunction: two had Klinefelter’s syndrome
and one had undergone bilateral orchidectomy. In seven of eight men
with ESRD, the renal disease was attributed to hypertension. In men
with ESRD, the average duration of hemodialysis was 47 months (range,
3–192 months). Patch tolerability and adverse experiences. The patches were well tolerated. Only one healthy hypogonadal man developed an erythematous rash at the patch application site; the rash disappeared in 3 days after changing the patch application site, and the subject continued treatment without further skin reactions. There were no significant changes in hemoglobin, AST and ALT, PSA, and plasma lipids during treatment (data not shown). One patient on maintenance hemodialysis experienced occlusion of the arterio-venous fistula due to thrombosis; this individual had experienced similar problems before his participation in this study.
Hormone levels
Total testosterone. In both groups of men, after application
of two patches, serum testosterone concentrations increased (Fig. 1 and Table 2) in
to the midrange for healthy young men. The Cmax and Cmin testosterone
concentrations during the 24-h patch application period were not
significantly different between healthy hypogonadal men and men with
ESRD (Table 2). The mean C’ss testosterone increment and increment in
testosterone concentrations from baseline to Cmax were not
significantly different between the two groups. Testosterone
bioavailability, calculated as baselinesubtracted AUC, was not
significantly different between healthy hypogonadal men and men with
ESRD (Table 2A).
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).
However, on the day of hemodialysis, there were no significant
differences between time-average serum total (742 ± 155
vs. 752 ± 105 ng/dL, P = 0.989)
testosterone concentrations during the 4 h immediately before
hemodialysis or during the period of hemodialysis (Fig. 3). To assess
whether the differences in serum testosterone concentrations on the
dialysis and interdialytic days were due to different degrees of
hemodilution, we measured serum albumin on several serum samples
obtained on these days. Serum albumin concentrations were not
significantly different on dialysis and interdialytic days (3.8 ±
0.1 vs. 3.6 ± 0.2 g/dL, P = 0.54). On
the day of hemodilaysis, serum albumin concentrations (3.4 ± 0.3
vs. 3.9 ± 0.1 g/dL, P = 0.052) and
testosterone to albumin ratios (210 ± 33 vs. 189
± 32, P = 0.886) were not significantly different
during the 4 h before hemodialysis and during hemodialysis.
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and Table 2B). Serum free testosterone
concentrations increased into the midnormal range after patch
application on day 28 in both groups of men (Fig. 2A and Table 2B). The
Css, Cmin, and Cmax were not significantly different between the two
groups of patients.
|
). The AUC’ was also not significantly
different between healthy hypogonadal men and men with ESRD (Table 2B).
The time-average increment (Css’), as well as increment from baseline
to Cmax in serum free testosterone concentrations were likewise not
significantly different between the two groups (Table 2B).
In men on hemodialysis, time-average serum free testosterone levels,
increment above baseline, and Cmax were numerically higher on dialysis
day, compared with interdialytic day, but these differences did not
achieve statistical significance (Table 3B). There were no significant
differences between time-average free testosterone levels during the
4 h before dialysis or during the period of hemodialysis (82
± 18 vs. 91 ± 18, pg/mL, P = 0.72,
Fig. 3B).
|
).
In men with ESRD, there was no significant difference in the half-lives
of total and free testosterone on days 22 and 29 (Table 4A).
|
).
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, from 6.6 to 3.3 U/L, P = 0.016 in healthy
hypogonadal men, and from 12.8 to 2.9 U/L, P = 0.069 in
men with ESRD). The degree of suppression was greater in men with ESRD,
compared with healthy hypogonadal men (mean suppression, 91 ± 3%
in men on hemodialysis vs. 57 ± 12% in healthy
hypogonadal men, P = 0.035).
Serum 17ß-estradiol. Serum 17ß-estradiol concentrations at
baseline were higher in men with ESRD than healthy hypogonadal men
(Table 5). During treatment, serum estradiol levels increased in both
groups but remained within the physiologic male range. Serum estradiol
concentrations on day 28 were significantly higher in men on
hemodialysis than healthy hypogonadal men.
Serum SHBG. Serum SHBG concentrations at baseline were higher
in men with ESRD than healthy hypogonadal men (Table 5). Serum SHBG
concentrations did not change significantly in either group of men
during testosterone treatment (Table 5).
Testosterone clearance during hemodialysis (Table 4B). The
total amount of testosterone cleared in the dialysate was small (mean,
8.4 µg) relative to the daily production rates of testosterone in
healthy young men (3–10 mg/day).
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A regimen of two testosterone patches applied daily can maintain serum total and free testosterone, DHT, and estradiol concentrations in the midnormal range in healthy, hypogonadal men and in men receiving maintenance hemodialysis. On this testosterone replacement regimen, the Css, Cmax, Cmin, AUC, AUC’, and t1/2 for total and free testosterone concentrations were not significantly different between the two groups of men. The increments in serum total and free testosterone levels during patch application in men on hemodialysis were not significantly different from those in healthy hypogonadal men. Only a small amount of testosterone was removed during hemodialysis; this amount is less than 0.15% of the daily production rates of testosterone.
The majority of participants in this study were either African-Americans or Hispanics, consistent with the demographics of the patient population served by our medical center. Ethnic differences in the testosterone metabolism and end organ responsiveness between Caucasians and Asians have been reported; we do not know whether African-Americans and Hispanics differ from Caucasians in their androgen metabolism (41, 42, 43, 44). Also, the mean age of men on hemodialysis was 10 yr higher than that of healthy, hypogonadal men. We do not know whether this age difference is clinically significant with respect to its effects on plasma testosterone clearance.
Current recommendations are to apply one 5-mg testosterone patch daily for androgen replacement therapy. This regimen, when administered to healthy hypogonadal men, increases mean serum total and free testosterone concentrations into the low normal range, although some hypogonadal men can achieve midnormal serum testosterone levels on this regimen (34, 35). Our data show that the application of two patches daily (10 mg/24 h) consistently raises average serum total and free testosterone concentrations into the midrange for healthy young men. We do not know what the optimum testosterone levels are in patients receiving testosterone replacement therapy. Testosterone dose-dependency of various androgen-dependent physiologic processes is unknown (45). However, if the objective of testosterone replacement is to raise serum total and free testosterone levels into the midnormal range, then a regimen of two testosterone patches will likely be more effective in achieving this objective than the currently recommended regimen of one 5-mg patch daily.
Although the baseline serum total and free testosterone levels were significantly higher in men on maintenance hemodialysis than healthy hypogonadal men, the time-average and maximal serum total and free testosterone concentrations were not significantly different between the two groups of men. The time-average increment and the baseline-subtracted area under the curve for total and free testosterone concentrations were not significantly different between the two groups. Men on hemodialysis experienced a greater percent suppression of LH during testosterone administration and might also have suppressed their endogenous testosterone production to a greater extent than healthy hypogonadal men. Because we used the baseline testosterone for calculation of the increments above baseline during treatment, we may have underestimated the actual increment in serum total and free testosterone levels on days 21 and 28 in men on hemodialysis.
The treatment regimen was well tolerated. There were no significant testosterone-related adverse events. One healthy hypogonadal man developed a rash at the patch application site. There were no significant changes in hemoglobin, AST, ALT, PSA, or plasma lipids in either group.
The amount of testosterone cleared in the dialysate during 4 h of hemodialysis was less than 0.15% of the daily production rate of testosterone in healthy young men. Therefore, low serum testosterone concentrations in men on hemodialysis cannot be explained on the basis of its removal during hemodialysis. Unbound testosterone readily crosses the dialysis membrane in vitro; the very small net clearance of testosterone from the blood in vivo during hemodialysis is presumably due to its tight binding to plasma proteins. Not surprisingly, there were no significant differences in total and free testosterone concentrations before and during dialysis. The half-life of circulating testosterone was not significantly different in men on hemodialysis, when compared with healthy hypogonadal men.
It is not apparent why in men on hemodialysis, total and free testosterone concentrations were higher on the dialysis day, as compared with the interdialytic day. This does not seem directly related to the hemodialysis process itself because serum total and free testosterone levels were not significantly different in the 4-h period preceding dialysis, compared with the 4 h of hemodialysis. This also cannot be explained by different degrees of hemodilution because serum albumin concentrations were not significantly different on the 2 days. It is possible that this might reflect variability in testosterone release or absorption from the patch on postdialysis days due to ultrafiltration-induced changes in skin turgor and absorptive properties.
Previous reports suggest that two thirds of men with ESRD might be hypogonadal (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12), defined in terms of low total and free testosterone concentrations. Of the 39 men with ESRD on hemodialysis, who were screened for these studies and did not have diabetes mellitus, 24 (63%) had serum total and free testosterone levels below the lower limit of normal male range. Androgen deficiency in men on hemodialysis is multifactorial; defects exist at all levels of the hypothalamic-pituitary-testicular axis (13, 14, 15, 16, 17, 18, 19, 20, 46, 47, 48, 49, 50, 51). There is a high prevalence of sexual dysfunction and spermatogenic abnormalities in men on hemodialysis (21). Muscle mass is decreased and fat mass is increased, and muscle performance and physical function are markedly impaired in men receiving hemodialysis. Whereas androgen deficiency might contribute to the complex pathophysiology of sexual dysfunction and sarcopenia in men on hemodialysis, we do not know if any of these physiologic derangements can be reversed by androgen replacement. These pharmacokinetic data set the stage for further studies to determine whether increasing serum testosterone levels of men on hemodialysis with low testosterone levels into the range that is midnormal for healthy young men will increase muscle mass, strength, and physical function.
Footnotes
1 Research support for this investigator-initiated project was
provided by a research grant from Alza Corp., Clinical
Trials Unit Grant U01-DK54047, Research Centers for Minority
Institutions (RCMI) Clinical Research Infrastructure Initiative
(P20RR11145), RCMI Grants G12RR03026 and U54RR14616, and NIH Grant
1RO1AG14369-01. 
Received September 15, 2000.
Revised December 28, 2000.
Revised February 1, 2001.
Accepted February 26, 2001.
References
subunit of the pituitary
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patients. J Clin Endocrinol Metab. 53:39–48.[Medline]
Androgen
glucosidurinates are not removed by hemodialysis in male uremic
patients. Proceedings of the 76th Annual Meeting of The Endocrine
Society, Anaheim, CA, 1994, p. 1305 (Abstract).
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, Serum total testosterone concentrations on
control day 0; 
, serum total testosterone concentrations during
testosterone treatment. The treatment day was day 28 in healthy
hypogonadal men and an interdialytic day (day 21 or 28) in men on
hemodialysis. The data are mean ± SEM. To convert
total testosterone concentrations from nanograms per dL to nanomoles
per L, multiply by 0.03467.
