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

Bicalutamide

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

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

Cyproterone acetate (with and without estrogens)

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

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

  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