This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Escobar-Morreale, H. F. Articles by Sancho, J. Search for Related Content PubMed PubMed Citation Articles by Escobar-Morreale, H. F. Articles by Sancho, J.

The Increased Circulating Prostate-Specific Antigen Concentrations in Women with Hirsutism Do Not Respond to Acute Changes in Adrenal or Ovarian Function

Departments of Endocrinology and Clinical Biochemistry (S.A., J.V.-P.), Hospital Ramón y Cajal, Madrid, Spain

Address all correspondence and requests for reprints to: Héctor F. Escobar-Morreale, M.D., Ph.D., Department of Endocrinology, Hospital Ramón y Cajal, Carretera de Colmenar Km 9,100, 28034 Madrid, Spain.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Serum prostate-specific antigen (PSA) is produced in several female tissues and appears to be up-regulated by androgens. We have studied serum PSA concentrations in women with different forms of hyperandrogenism, focusing on the influence of changes in ovarian and adrenal function on these concentrations.

Thirty-seven hirsute women were studied in the follicular phase of the menstrual cycle. Basal and ACTH-stimulated plasma samples were obtained, and sampling was repeated 1 (gonadal stimulation) and 21 (gonadal suppression) days after receiving a single im 3.75-mg dose of triptorelin. Eleven nonhyperandrogenic women served as controls.

Hirsute women had increased PSA levels compared to controls. When considering the source of the hyperandrogenism, ovarian patients (those with increased serum androgen levels that normalized during gonadal suppression) and adrenal patients (those with increased androgen levels that remained elevated during gonadal suppression) presented increased PSA values, whereas hirsute patients without hyperandrogenemia had normal PSA levels. PSA levels did not change during ovarian or adrenal stimulation or during gonadal suppression with respect to initial values. Basal PSA levels showed significant correlations with basal total testosterone (r = 0.59; P < 0.001), free androgen index (r = 0.68; P < 0.001), sex hormone-binding globulin (r = -0.58; P < 0.001), dehydroepiandrosterone sulfate (r = 0.39; P < 0.01), 17-hydroxyprogesterone (r = 0.32; P < 0.05), and age (r = -0.33; P < 0.05) when patients and controls were considered as a whole.

In conclusion, basal PSA levels are increased in hirsute patients and correlate with the degree of hyperandrogenism when patients and controls are considered as a whole. The adrenal and the ovary do not appear to be the source of PSA, suggesting that hyperandrogenism induces PSA secretion in tissues other than the adrenal and the ovary.

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
PROSTATE-SPECIFIC antigen (PSA) is a 33-kDa serine protease that is primarily produced by prostatic tissue and secreted into the seminal plasma. Initially, PSA was believed to be a highly specific marker for normal or cancerous prostatic tissue, but recent studies have also found PSA in female tissues and fluids such as breast, ovary, milk, and amniotic fluid (1). The gene expression and protein production of PSA in nonprostatic tissues are under the regulation of steroid hormones. Androgens, glucocorticoids, and progestins up-regulate PSA gene expression, resulting in increased protein production (2). Estrogen by itself seems to have no effect on PSA regulation, but it can impair androgen-induced PSA production (2). Nonprostatic PSA has been suggested to play a role in the management of several breast diseases, such as cancer (3), fibroadenomas, and cysts (4). With the development of an ultrasensitive PSA assay, Melegos et al. (5) found increased serum PSA levels in a significant number of women with hirsutism, showing a significant direct correlation with serum androstanediol glucuronide, an androgen metabolite. In this preliminary study, PSA was suggested to be a marker of hyperandrogenism in hirsute women. However, little information was provided regarding the clinical characteristics of the hirsute women included in this study (5), such as the phase of the menstrual cycle when the samples were obtained, the source of the hyperandrogenism of the patients, or previous hormonal treatments. Moreover, no insight into the origin of the increased serum PSA in hirsute patients was provided by the results (5).

In the present study we measured serum PSA concentrations in a group of untreated hirsute women classified as having adrenal, ovarian, or idiopathic hirsutism according to combined ACTH and GnRH analog testing (6). The influence of changes in adrenal and ovarian function on serum PSA concentrations as well as the possible relationships between PSA and several adrenal and ovarian steroids were also evaluated.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Subjects

Thirty-seven hirsute women were included in the study. Hirsutism was defined by excessive body hair distributed in an androgen-dependent pattern, with a Ferriman-Gallwey score (7) greater than 7 (range, 8–34; mean ± SEM, 15.6 ± 0.9). None of the patients was hypertensive or had evidence of Cushing’s disease or drug-induced hirsutism. Hyperprolactinemia, thyroid disease, acromegaly, and nonclassical congenital adrenal hyperplasia were ruled out by appropriate testing. The reference values for the analytical procedures were obtained from a control group of 11 normal menstruating women, without signs and symptoms of hyperandrogenism or family history of endocrine diseases. Menstrual cycle intervals were evaluated on recall for every patient and control subject. Oligomenorrhea was defined by the presence of three or more cycles of more than 35 days in the previous 6 months, and amenorrhea by lack of vaginal bleeding for 3 months. None of the patients or controls had taken hormonal medications, including contraceptive pills, for the last 6 months. The study was approved by the hospital ethical committee, and informed consent was obtained from each patient and control. Data regarding the adrenal and ovarian steroid profiles from some of the patients and controls have been included in previous publications (8, 9, 10).

Experimental design

The experimental design has been recently described in detail (10). In brief, women were studied during the follicular phase, between days 5–10 of the menstrual cycle, or in one patient during amenorrhea after excluding gestation by appropriate testing. Patients reported to the endocrine-metabolic testing room between 0800–0900 h after a 12-h overnight fasting. An indwelling iv line was placed in a forearm vein, and after 15–30 min, basal blood samples were obtained for the determination of PSA, total testosterone (T), sex hormone-binding globulin (SHBG), and estradiol (E₂). Immediately after taking basal samples, a 250-µg iv bolus of ACTH-(1–24) (Synacthen, Ciba-Geigy, Basel, Switzerland) was injected, and blood samples were obtained at 0 and 60 min for determinations of cortisol, 11-deoxycortisol, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate (DHEAS), and ⁴-androstenedione. After obtaining the 60 min sample from the ACTH test, a 100-µg iv bolus of GnRH (Luforan, Serono, Madrid, Spain) was injected, and blood samples for LH and FSH determinations were obtained at 0 and 30 min. A single dose (3.75 mg, im) of triptorelin (D-Trp⁶-GnRH, Decapeptyl, LASA-Ipsen, Barcelona, Spain) was then administered. Basal sampling and the ACTH test were repeated the next day (day 1) and also, together with a GnRH test, 21 days after triptorelin administration (day 21). As has been previously shown (10, 11), triptorelin administration results in stimulation of the gonadal axis by day 1 and suppression of the gonadal axis by day 21, which were confirmed by measurements of serum basal E₂ and basal and GnRH-stimulated LH and FSH in all of the patients studied here (Fig. 1, lower 3 panels). According to the response of serum androgen levels to gonadal suppression, patients were classified as having idiopathic hirsutism, when normal androgen levels were present before and during ovarian suppression, functional ovarian hyperandrogenism, when the initially elevated androgen levels returned to normal during ovarian suppression, or functional adrenal hyperandrogenism, when hyperandrogenism persisted during gonadal suppression (6).

View larger version (20K): [in this window] [in a new window]   Figure 1. Changes in basal serum PSA, T, SHBG, E2, LH, and FSH concentrations and the free androgen index (FAI) at baseline (day 0), day 1, and day 21 after im administration of a single 3.75-mg dose of triptorelin. For serum PSA analysis, Friedman’s two-way ANOVA followed by repeated Wilcoxon matched pairs, signed rank test, adjusting the level of significance for multiple comparisons, were used. The parentheses include the median values of serum PSA concentrations, which do not follow a normal distribution. The changes in other variables were analyzed by repeated measures multivariate ANOVA followed by repeated paired t tests when significant differences were found. *, At least P < 0.05 compared to baseline and day 1. , At least P < 0.05 compared to baseline.

Assays

Serum PSA concentrations were analyzed by an ultrasensitive chemiluminescent enzyme immunoassay (Immulite Third Generation PSA, Diagnostic Products Corp., Los Angeles, CA) with a lower limit of detection of less than 2 pg/mL (12). As serum PSA levels in women are usually very low, near the limit of detection of the assay (5), all serum samples were analyzed for PSA within a single assay to avoid interassay variations. The intraassay coefficients of variation for 3.5, 12, and 25 pg/mL samples were determined in our laboratory and were 15.2%, 11.6%, and 13.0%, respectively. T, SHBG, cortisol, 11-deoxycortisol, cortisol, 11-deoxycortisol, progesterone, 17-hydroxyprogesterone, DHEAS, ⁴-androstenedione, LH, FSH, and E₂ were assayed as previously reported (8, 9, 10). The free androgen index was calculated using the formula: [T (nmol/L) x 100]/SHBG (nmol/L).

Ultrasonography

Transparietal abdominal and pelvic ultrasonography was performed in every patient using a Toshiba 3.75-megahertz transducer (Tosbee SSA-240, Toshiba Medical Systems, Tokyo, Japan), and diagnosis of polycystic ovaries was based on published criteria (13).

Statistical analysis

Nonparametric tests were used when analyzing serum PSA levels, which were not adjusted to a normal distribution. Serum PSA values are expressed as mean (median) ± SEM in text, tables, and figures. To compare the different groups of hirsute patients among themselves and with the control group, Kruskal-Wallis one-way ANOVA was used. The individual comparisons between the pairs of groups were made by multiple Mann-Whitney U rank sum W tests, adjusting the level of significance downward (14). The changes in PSA concentrations during the changes in ovarian and adrenal function were evaluated by Friedman’s two-way ANOVA, followed by repeated Wilcoxon matched pairs, signed rank test, adjusting the level of significance for multiple comparisons as stated above. The correlations between serum PSA and other variables were analyzed by Spearman’s nonparametric correlation analysis. When the variables were adjusted to a normal distribution, repeated measures multivariate ANOVA was used to evaluate the evolution of the patient’s hormonal variables during sequential gonadal stimulation and suppression. Paired t tests were used to identify these differences only when the result of the repeated measures multivariate ANOVA was significant.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Baseline serum PSA concentrations in hirsute women and controls

Serum PSA concentrations were clearly increased in hirsute women compared to control values (Fig. 2). In fact, PSA levels were detectable in 32 of the 37 hirsute patients, whereas only 4 of the control women had measurable PSA concentrations. No difference in age was found between patients and controls (23.0 ± 1.2 vs. 27.5 ± 1.2 yr; nonsignificant), although patients had a higher body mass index than control women (25.2 ± 0.8 vs. 21.2 ± 0.8 kg/m²; P < 0.050).

View larger version (33K): [in this window] [in a new window]   Figure 2. Serum PSA concentrations in hirsute patients and control women. The columns represent the mean ± SEM of the groups. Values in parentheses represent the median of the groups. IH, Idiopathic hirsutism; FOH, functional ovarian hyperandrogenism; FAH, fFunctional adrenal hyperandrogenism. *, At least P < 0.05 compared to the control group by Kruskal-Wallis’ one-way ANOVA followed by multiple Mann-Whitney U rank sum W tests, adjusting the level of significance downward.

Lack of an influence of the changes in gonadal and adrenal function on serum PSA levels

When studying all of the patients together, the changes in gonadal function did not result in any change in PSA concentrations despite marked stimulation by day 1 and profound suppression by day 21 of E₂ and gonadotropin levels (Fig. 1). The free androgen index was increased and SHBG was decreased during gonadal stimulation by day 1 (Fig. 1), whereas serum T levels and the free androgen index decreased during ovarian suppression by day 21 (Fig. 1). When the different groups of patients were considered separately, the only change found in PSA values was an increase by day 1 with respect to the baseline value in the idiopathic group [4.2 (4.0) ± 1.1 vs. 9.2 (6.0) ± 2.0 pg/mL; P < 0.05] and a return to baseline levels [4.6 (3) ± 0.8] by day 21. No change in serum PSA levels were found in the ovarian and adrenal groups during gonadal stimulation and suppression. Serum PSA concentrations did not change in response to ACTH stimulation in either patients or controls (Table 1).

Obese patients, as defined by a body mass index greater than 25 kg/m², had higher serum PSA levels [obese, 12.8 (7) ± 5.4; lean, 6.2 (4.0) ± 1.5 pg/mL; P < 0.050) together with a higher free androgen index (11.3 ± 2.8 vs. 6.2 ± 0.8; P < 0.050), lower SHBG levels (266 ± 36 vs. 451 ± 41 µg/dL; P < 0.005), and similar T concentrations (71 ± 11 vs. 71 ± 4 ng/dL; nonsignificant). None of the four controls with detectable serum PSA levels was obese.

Relationship of basal serum PSA levels to clinical and biochemical parameters of hirsutism

The clinical characteristics, Ferriman-Gallwey scores, and baseline androgen concentrations of the different groups of hirsute women are described in Table 2. There were no statistically significant differences in age, body mass index, Ferriman-Gallwey scores, or prevalences of menstrual disturbances and ultrasonographic polycystic ovaries among women with idiopathic hirsutism, ovarian hyperandrogenism, and adrenal hyperandrogenism (Table 2). Obviously, patients with ovarian or adrenal hyperandrogenism had higher baseline serum androgen levels than women with idiopathic hirsutism (Table 2). The basal serum PSA concentrations of the patients were not different depending on the presence of ultrasonographic polycystic ovaries (Mann-Whitney U-Wilcoxon rank sum W = 291; nonsignificant) or depending on the presence of menstrual disturbances (Mann-Whitney U-Wilcoxon rank sum W = 341; nonsignificant).

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

Serum PSA levels were clearly elevated in hirsute patients compared to those in normal control women. In fact, 86.5% of the patients with hirsutism presented detectable serum PSA levels compared to less than half of the subjects in the control group. The results presented here suggest that the increase in serum PSA is mainly related to the degree of hyperandrogenism of the patients. 1) The group of hirsute women without significant hyperandrogenemia showed PSA values that were not different from those in control women, whereas patients with adrenal or ovarian hyperandrogenism had elevated PSA levels. 2) Serum PSA levels strongly correlated with serum androgen levels. 3) No correlation was observed with serum E₂ levels.

Obesity might have played a role in the increase in serum PSA found in hirsute women, as the body mass index was higher in patients than in controls, and obese patients had higher PSA levels than lean patients. However, the lack of a direct correlation between serum PSA concentrations and body mass index together with the presence of higher androgen levels in obese patients compared to lean patients also suggest that the influence of obesity on serum PSA could be due to the strong correlations among PSA, the free androgen index, and SHBG. On the contrary, age and menstrual status do not appear to have affected our results. Although we found age and serum PSA to be inversely related, a finding also reported by Melegos et al. (5), age was similar in patients and controls in our series. The increase in serum PSA was not related to the presence or absence of menstrual disturbances in either our series or the patients reported by Melegos et al. (5). The phase of the menstrual cycle in which samples were taken, which was not recorded in the preliminary study by Melegos et al. (5), ought to be considered as a possible confounding factor, as the highest PSA concentrations are found during the mid- to late follicular phase, and the lowest are found during the mid- to late luteal phase (17). As basal sampling was performed in the midfollicular phase in both patients and controls, the increase in serum PSA found in our patients could not be attributed to differences in the phase of the menstrual cycle.

Our experimental design has also permitted us to investigate to some extent the source of the increased secretion of PSA in hyperandrogenic patients. As stated above, the adrenal and the ovary could be sources of PSA, as PSA is expressed in tumors from these tissues (1). However, the data presented here do not support these tissues as sources of the increased PSA. On the one hand, serum PSA showed no change in response to ACTH stimulation, which results in marked increases in glucocorticoid and androgen concentrations (6, 8, 9). On the other hand, neither stimulation nor suppression of the gonadal axis resulted in consistent changes in serum PSA. Moreover, correction of the androgen excess in women with functional ovarian hyperandrogenism during triptorelin-induced gonadal suppression did not result in a decrease in serum PSA. This finding suggests that the influence of serum androgens on PSA secretion might persist for some time after correction of hyperandrogenism, as occurs with other biological end points of androgen excess, such as hirsutism. Thus, the source of PSA appears to be a tissue or organ other than the adrenal or ovary that is stimulated by a chronic and prolonged androgen excess to secrete excessive amounts of PSA into the circulation. The breast (1) or the paraurethral glands (18, 19) could secrete PSA in response to a certain androgen excess, but the definite identification of the source of PSA secretion in hirsute patients requires further extensive studies.

Finally, our results suggest that serum PSA might be a useful marker of androgen excess in hirsute patients. In fact, PSA levels were increased in most women with hirsutism, even in several patients in whom levels of the main serum androgens, T, ⁴-androstenedione, and DHEAS, were within the normal range. We have previously shown that in nearly all hirsute women, mild defects in adrenal and/or ovarian steroidogenesis can be found even in the absence of basal hyperandrogenemia (8). These subtle abnormalities might lead to androgen excess at the tissue level, resulting in increases in PSA secretion and serum PSA concentrations. However, the possible role of serum PSA levels in the diagnosis of hirsutism and in the monitoring of its treatment remains to be elucidated.

	Acknowledgments

 
The authors thank Ms. Genoveva González her technical assistance, and are gratefully indebted to Diagnostic Products Corporation-DIPESA (Madrid, Spain) for kindly supplying free of charge the reagents used for serum PSA measurements.

	Footnotes

 
¹ Present address: Section of Endocrinology, Hospital General Universitario, Alicante, Spain.

Received January 13, 1998.

Revised March 11, 1998.

Accepted April 8, 1998.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Diamandis EP. 1996 Prostate specific antigen–new applications in breast and other cancers. Anticancer Res. 16:3983–3984.[Medline]
2. Diamandis EP, Yu H. 1997 Nonprostatic sources of prostate-specific antigen. Urol Clin North Am. 24:275–282.[CrossRef][Medline]
3. Giai M, Yu H, Roagna R, et al. 1995 Prostate-specific antigen in serum of women with breast cancer. Br J Cancer. 72:728–731.[Medline]
4. Borchert GH, Giai M, Diamandis EP. 1997 Elevated levels of prostate-specific antigen in serum of women with fibroadenomas and breast cysts. J Natl Cancer Inst. 89:587–588.[Free Full Text]
5. Melegos DN, Yu H, Ashok M, Wang C, Stanczyk F, Diamandis EP. 1997 Prostate-specific antigen in female serum, a potential new marker of androgen excess. J Clin Endocrinol Metab. 82:777–780.[Abstract/Free Full Text]
6. Escobar-Morreale H, Pazos F, Potau N, Garcia Robles R, Sancho JM, Varela C. 1994 Ovarian suppression with triptorelin and adrenal stimulation with adrenocorticotropin in functional hyperadrogenism: role of adrenal and ovarian cytochrome P450c17 alpha. Fertil Steril. 62:521–530.[Medline]
7. Ferriman D, Gallwey JD. 1961 Clinical assessment of body hair growth in women. J Clin Endocrinol Metab. 21:1440–1447.
8. Escobar-Morreale HF, Serrano Gotarredona J, García Robles R, Sancho J, Varela C. 1997 Mild adrenal and ovarian steroidogenic abnormalities in hirsute women without hyperandrogenemia: does idiopathic hirsutism exist? Metabolism. 46:902–907.[CrossRef][Medline]
9. Escobar-Morreale HF, Serrano-Gotarredona J, García-Robles R, Sancho J, Varela C. 1997 Lack of an ovarian function influence on the increased adrenal androgen secretion present in women with functional ovarian hyperandrogenism. Fertil Steril. 67:654–662.[CrossRef][Medline]
10. Escobar-Morreale HF, Serrano-Gotarredona J, Varela C, García-Robles R, Sancho JM. 1997 Circulating leptin concentrations in women with hirsutism. Fertil Steril. 68:898–906.[CrossRef][Medline]
11. Castelo Branco C, Martinez de Osaba MJ, Martinez S, Fortuny A. 1996 Effects of a long-acting gonadotropin-releasing hormone analog on the pituitary-ovarian-adrenal axis in women with severe hirsutism. Metabolism. 45:24–27.
12. Witherspoon LR, Lapeyrolerie T. 1997 Sensitive prostate specific antigen measurements identify men with long disease-free intervals and differentiate aggressive from indolent cancer recurrences within 2 years after radical prostatectomy. J Urol. 157:1322–1328.[CrossRef][Medline]
13. Adams J, Polson DW, Abdulwahid N, et al. 1985 Multifollicular ovaries: clinical and endocrine features and response to pulsatile gonadotropin releasing hormone. Lancet. 2:1375–1379.[Medline]
14. Dawson-Saunders B, Trapp RG. 1990 Basic and clinical bioestatistics. East Norwalk: Appleton and Lange.
15. Diamandis EP, Yu H, Melegos DN. 1996 Ultrasensitive prostate specific antigen assays and their clinical application. Clin Chem. 42:853–857.[Free Full Text]
16. Ferguson RA, Yu H, Kalyvas M, Zammit S, Diamandis EP. 1996 Ultrasensitive detection of prostate-specific antigen by a time-resolved immunofluorometric assay and the Immulite® immunochemiluminiscent third generation assay: potential applications in prostate and breast cancer. Clin Chem. 42:675–684.[Abstract/Free Full Text]
17. Zarghami N, Grass L, Sauter ER, Diamandis EP. 1997 Prostate-specific antigen in serum during the menstrual cycle. Clin Chem. 43:1862–1867.[Abstract/Free Full Text]
18. Tepper SL, Jagirdar J, Heath D, Geller SA. 1984 Homology between the female paraurethral (Skene’s) glands and the prostate. Immunohistochemical demonstration. Arch Pathol Lab Med. 108:423–425.[Medline]
19. Dodson MK, Cliby WA, Keeney GL, Peterson MF, Podratz KC. 1994 Skene’s gland adenocarcinoma with increased serum level of prostate-specific antigen. Gynecol Oncol. 55:304–307.[CrossRef][Medline]

This article has been cited by other articles:

				M. H. Slagter, A. Scorilas, L. J.G. Gooren, W. de Ronde, A. Soosaipillai, E. J. Giltay, M. Paliouras, and E. P. Diamandis Effect of Testosterone Administration on Serum and Urine Kallikrein Concentrations in Female-to-Male Transsexuals Clin. Chem., August 1, 2006; 52(8): 1546 - 1551. [Abstract] [Full Text] [PDF]

				H. Aksoy, F. Akcay, Z. Umudum, A. K. Yildirim, and R. Memisogullari Changes of PSA Concentrations in Serum and Saliva of Healthy Women during the Menstrual Cycle Ann. Clin. Lab. Sci., January 1, 2002; 32(1): 31 - 36. [Abstract] [Full Text] [PDF]

				A. Mifsud, A. T. Choon, D. Fang, and E.L. Yong Prostate-specific antigen, testosterone, sex-hormone binding globulin and androgen receptor CAG repeat polymorphisms in subfertile and normal men Mol. Hum. Reprod., November 1, 2001; 7(11): 1007 - 1013. [Abstract] [Full Text] [PDF]

				C. V. Obiezu, A. Scorilas, A. Magklara, M. H. Thornton, C. Y. Wang, F. Z. Stanczyk, and E. P. Diamandis Prostate-Specific Antigen and Human Glandular Kallikrein 2 Are Markedly Elevated in Urine of Patients with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., April 1, 2001; 86(4): 1558 - 1561. [Abstract] [Full Text]

				H. F. Escobar-Morreale, S. Ávila, and J. Sancho Serum Prostate-Specific Antigen Concentrations Are Not Useful for Monitoring the Treatment of Hirsutism with Oral Contraceptive Pills J. Clin. Endocrinol. Metab., July 1, 2000; 85(7): 2488 - 2492. [Abstract] [Full Text]

				C. V. Obiezu, E. J. Giltay, A. Magklara, A. Scorilas, L. J.G. Gooren, H. Yu, D. J.C. Howarth, and E. P. Diamandis Serum and Urinary Prostate-specific Antigen and Urinary Human Glandular Kallikrein Concentrations Are Significantly Increased after Testosterone Administration in Female-to-Male Transsexuals Clin. Chem., June 1, 2000; 46(6): 859 - 862. [Abstract] [Full Text] [PDF]

				R. M. Calvo, M. Asunción, J. Sancho, J. L. San Millán, and H. F. Escobar-Morreale The Role of the CAG Repeat Polymorphism in the Androgen Receptor Gene and of Skewed X-Chromosome Inactivation, in the Pathogenesis of Hirsutism J. Clin. Endocrinol. Metab., April 1, 2000; 85(4): 1735 - 1740. [Abstract] [Full Text]

				C. Negri, F. Tosi, R. Dorizzi, A. Fortunato, G. G. Spiazzi, M. Muggeo, R. Castello, and P. Moghetti Antiandrogen Drugs Lower Serum Prostate-Specific Antigen (PSA) Levels in Hirsute Subjects: Evidence That Serum PSA Is a Marker of Androgen Action in Women J. Clin. Endocrinol. Metab., January 1, 2000; 85(1): 81 - 84. [Abstract] [Full Text]

				V. H. H. Goh Breast Tissues in Transsexual Women-A Nonprostatic Source of Androgen Up-Regulated Production of Prostate-Specific Antigen J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3313 - 3315. [Abstract] [Full Text]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Escobar-Morreale, H. F. Articles by Sancho, J. Search for Related Content PubMed PubMed Citation Articles by Escobar-Morreale, H. F. Articles by Sancho, J.