Prostate-specific antigen

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Prostate-specific antigen (PSA) is a protein present in humans. It is encoded by the gene KLK3,[1] which is regulated by androgens through the androgen receptor, and, as such, is used as a biomarker for androgen receptor activity.[2][3] It is closely related to HK2, another protein regulated by androgens.[3] It is present in high concentrations in both male and female ejaculate[4] as well as in blood in much lower concentrations.[5]

Response to antiandrogens[edit]

Bicalutamide[edit]

Bicalutamide inhibits PSA levels via androgen receptor antagonism[6][7] (specifically, by preventing AR from activating KLK3).

The following table shows the response of PSA levels to varying doses of bicalutamide in prostate cancer patients.[7] Note that prostate cancer can significantly increase PSA production, as PSA is primarily produced in the prostate. As a result, the response curve given in this table may not readily generalize to people without prostate cancer.

Bicalutamide dose (mg/day) % PSA decline
10 57
30 73
50 90
100 97
150 97

5α-Reductase inhibitors[edit]

5α-Reductase inhibitors (e.g. finasteride, dutasteride) inhibit PSA levels by about 50%[8] by decreasing DHT concentration.

Cyproterone acetate (with and without estrogens)[edit]

Trans women aged 18-50 years (median 30 years) treated with 100 mg/day cyproterone acetate had the following PSA response:[9]

Median plasma PSA Mean plasma PSA Median urine PSA
Baseline 4 months 12 months Baseline 4 months 12 months Baseline 4 months 12 months
Treatment Subjects ng/mL ng/mL change ng/mL change ng/mL ng/mL change ng/mL change ng/mL ng/mL change ng/mL change
100 mg/day CPA 10 0.333 0.035 -89% - - - - - - - 10.064 1.124 -89% - -
100 mg/day CPA and
17β-estradiol patch twice weekly
15 0.272 0.041 -85% - - - - - - - 19.885 0.092 -99.5% - -
100 mg/day CPA and
100 ug/day oral ethinylestradiol
31 0.296 0.025 -92% 0.01a -97%a 0.327 0.058 -82% 0.015 -95% 30.138 0.438 -99% 0.251a -98%a

a Only 17 of the original 31 subjects were analyzed at the 12 month mark.

Reference ranges[edit]

The following reference ranges are for serum concentrations. Serum PSA levels may be increased by prostatitis,[10] benign prostatic hyperplasia (BPH),[10] and recent ejaculation[11].

Population Age Range (ng/mL) Notes
Cis men[12] <50 0.3-2.5 90% CI
50-59 0.3-4.7
60-69 0.3-8.3
>70 0.4-17.8
Cis men with
prostate cancer[12]
<50 0.4-163.0
50-59 1.2-372.5
60-69 1.7-253.2
>70 2.3-613.2
Cis men[5] ? 1-2
Cis men with
prostate cancer,
BPH, or prostatitis[5]
? 3-4
Cis women[5][13] ? 0.002 Median
Cis women with
hyperandrogenic
syndromes[5]
? <0.6

References[edit]

  1. Uhlén M et al. "Tissue expression of KLK3 - The Human Protein Atlas". https://www.proteinatlas.org/ENSG00000142515-KLK3/tissue
  2. Sang Y, Myers M, Brown M (2002). "Formation of the Androgen Receptor Transcription Complex". Molecular Cell. 9(3): 601-610. https://doi.org/10.1016/S1097-2765(02)00471-9
  3. 3.0 3.1 K. Clint Cary et al (2013). "Biomarkers in prostate cancer surveillance and screening: past, present, and future". Therapeutic Advances in Urology. 5 (6): 318–329. doi:10.1177/1756287213495915. PMC 3825107. PMID 24294290. ISSN 1756-2872.
  4. Wimpissinger F, Stifter K, Grin W, Stackl W (2007). "The Female Prostate Revisited: Perineal Ultrasound and Biochemical Studies of Female Ejaculate". 4 (5): 1388-1393. https://doi.org/10.1111/j.1743-6109.2007.00542.x
  5. 5.0 5.1 5.2 5.3 5.4 Borchert G H, Giai M, Diamandis E P (1997 Apr 16). "Elevated Levels of Prostate-Specific Antigen in Serum of Women With Fibroadenomas and Breast Cysts". 89 (8): 587-588. https://doi.org/10.1093/jnci/89.8.587
  6. Cockshott I D (2004). "Bicalutamide: clinical pharmacokinetics and metabolism". Clinical Pharmacokinetics. 43 (13): 855–878. https://doi.org/10.2165/00003088-200443130-00003
  7. 7.0 7.1 Blackledge, G (1993). Casodex--mechanisms of action and opportunities for usage. Cancer, 72: 3830-3833. https://www.ncbi.nlm.nih.gov/pubmed/7504578
  8. "FDA Drug Safety Communication: 5-alpha reductase inhibitors (5-ARIs) may increase the risk of a more serious form of prostate cancer". Retrieved 2018-03-07. https://www.fda.gov/Drugs/DrugSafety/ucm258314.htm
  9. Christina V. Obiezu et al (2000). "DRAMATIC SUPPRESSION OF PLASMA AND URINARY PROSTATE SPECIFIC ANTIGEN AND HUMAN GLANDULAR KALLIKREIN BY ANTIANDROGENS IN MALE-TO-FEMALE TRANSSEXUALS". The Journal of Urology. 163 (3): 802–805. doi:10.1016/S0022-5347(05)67808-1. ISSN 00225347.
  10. 10.0 10.1 Nadler R B, Humphrey P A, Smith D S, Catalona W J, Ratliff T L (Aug 1995). "Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels". The Journal of Urology. 154 (2 Pt 1): 407-413. https://doi.org/10.1016/S0022-5347(01)67064-2
  11. Herschman J D, Smith D S, Catalona W J (Aug 1997). "Effect of ejaculation on serum total and free prostate-specific antigen concentrations". Urology. 50 (2): 239-243. https://doi.org/10.1016/S0090-4295(97)00209-4
  12. 12.0 12.1 Connolly D, Black A, Murray L, Gavin A, Keane P (2007). "798 Population Based Age-Specific Reference Ranges for PSA". European Urology Supplements. 6 (2): 222. https://doi.org/10.1016/S1569-9056(07)60793-3
  13. Diamandis E P, Yu H, Melegos D N (1996). "Ultrasensitive Prostate-Specific Antigen Assays And Their Clinical Application". Clin Chem. 42 (6): 853-857. https://www.ncbi.nlm.nih.gov/pubmed/8665675