Men's Health

Men's Health, Cancer Screening

PSA and free PSA (fPSA)Prostate cancer is a leading cause of cancer mortality. The American Cancer Society estimates that approximately 288,300 new cases will be diagnosed and 34,700 will die from prostate cancer in 2023 in the United States.7PSA, a serine protease, is produced by the epithelial cells of the prostate, and is produced by both benign and malignant cells. Abnormalities in the prostate gland architecture resulting from trauma or disease can lead to "leakage" of PSA into the bloodstream. Serum PSA exists primarily in either the free "non-complexed form" (fPSA) or in a "complex"(cPSA) primarily with the serum protease inhibitor, alpha 1-antichymotrypsin.8,9Typically, from 70 to 90 percent of the PSA in serum is cPSA, with the remainder being fPSA.10The %fPSA (ratio of fPSA to PSA) in serum has been demonstrated to significantly improve the discrimination of prostate cancer from benign prostatic conditions, especially in patients with PSA levels in the ≥4 to ≤10 ng/mL range. A higher %fPSA in serum is correlated with a lower probability of prostate cancer, while %fPSA values below 10 percent are more highly associated with cancer.10-12p2PSAProPSA and BPSA represent distinct forms of fPSA that demonstrate greater disease-association than PSA, fPSA, or cPSA alone.9Truncated forms of proPSA were found to be elevated in peripheral zone cancer tissue compared with BPH tissues.13The proPSA was elevated in prostate tumor tissue compared with BPH tissues.13The proPSA was elevated in prostate tumor tissue, while BPSA was elevated in nodular BPH transition zone tissue, compared to its concentration in peripheral zone tissue. ProPSA has been found as the native proPSA form containing a 7 amino acid pro leader peptide ([-7]proPSA),14as well as forms with truncated pro leader peptides. Truncated proPSA forms consist primarily of proPSA with a 5 amino acid pro leader peptide ([-5]proPSA), 4 amino acids ([-4]proPSA) and 2 amino acids (p2PSA).15,16The p2PSA has received the most attention since it was the primary form found in tumor extracts and shows higher immunostaining in prostate tumor than benign tissue.10,17Additionally, in vitro the most stable of the five identified proPSA forms is p2PSA.18,19Access Hybritech p2PSA was developed by Beckman Coulter, Inc. to measure p2PSA in serum. In studies of men with biopsy confirmed prostate cancer, p2PSA in the ≥4.0 to ≤10.0 ng/mL PSA range was shown to improve the specificity for cancer detection relative to %fPSA alone.10Reports from the literature are consistent with the intended use for the Access Hybritech p2PSA assay, used in conjunction with Access Hybritech PSA and fPSA assays to calculate the prostate health index (phi)in the further evaluation of patients with PSA levels in the ≥4.0 to ≤10.0 ng/mL range. Literature reports support the conclusion that precursor forms of PSA are emerging as potentially important diagnostic serum markers to augment PSA and improve prostate cancer detection.10,20-22Results of the Beckman Coulter, Inc. multi-center pivotal clinical trial found that Beckman Coulterphivalues significantly enhanced the clinical specificity relative to PSA and %fPSA for prostate cancer detection in the ≥4.0 ng/mL to ≤10.0 ng/mL PSA range.3At 95 percent clinical sensitivity, the clinical specificity for Beckman Coulterphiwas 14.1 percent compared to 9.9 percent for %fPSA. At 90 percent clinical sensitivity, the clinical specificity for Beckman Coulterphiwas 31.1 percent. At 80 percent clinical sensitivity, the clinical specificity for Beckman Coulterphiwas 46.1 percent. The improvement in clinical specificity for Beckman Coulterphirelative to %fPSA represents a substantial improvement in testing intended as an aid in distinguishing prostate cancer from benign prostatic conditions in men aged 50 years and older with total PSA ≥4.0 to ≤10.0 ng/mL, with digital rectal examination findings that are not suspicious for cancer.Beckman Coulterphiis anin vitroDiagnostic Multivariate Index Assay (IVDMIA), a combination of the results from the Access Hybritech PSA, free PSA and p2PSA assays designed to optimize clinical sensitivity and specificity as an aid in distinguishing prostate cancer from benign prostatic conditions. Beckman Coulterphiis used as an aid in distinguishing prostate cancer from benign prostatic conditions. A multi-center (seven clinical sites) clinical trial with a combination of prospective (97 percent) and retrospective (3 percent) subjects was conducted to test the effectiveness of Beckman Coulterphi. Subjects included men who were being evaluated to determine their prostate status.All subjects were between 50 and 84 years of age, with serum PSA values between 4 and 10 ng/mL (Hybritech calibration) and digital rectal examination (DRE) findings that were not suspicious for cancer. These men represent the "diagnostic gray zone," in which PSA has identified the men as high risk (25 percent cancer rate in men above 50 years of age), but where clinical specificity could be improved.23-25The study was blinded; clinicians did not have access to Beckman Coulterphivalues, and laboratory technicians did not have access to diagnoses. Inclusion criteria included subjects who signed informed consent, men ≥ 50 years of age, subjects who were untreated for prostate disease at the time of their blood draw, Hybritech PSA ≥4.0 and ≤10.0 ng/mL and ≤6 core biopsy. TRUS guided needle biopsy and diagnosis was histologically confirmed.Of the 658 total evaluable subjects, 652 (99.1 percent) had ≥8 core biopsies; 644 (97.9 percent) of the subjects had ≥10 core biopsies. Exclusion criteria included: prior history of prostate cancer, use of Avodart or Proscar at any time prior to blood draw, use of other drugs or therapies or recent prostatic manipulation that might have affected PSA values in the three months preceding the blood draw (including Propecia and androgen therapy including testosterone or Androgel), acute prostatitis, urinary tract infection, prior transurethral resection of the prostate (TURP), equivocal biopsy results, DRE with discrete nodules suspicious for cancer or PSA <4.0 or >10.0 ng/mL.A total of 658 men participated in the study (324 with prostate cancer and 334 without prostate cancer). Median age for both cancer and benign disease subjects was 63 years.Individual Patient Probability of Prostate Cancer on BiopsyBeckman Coulterphimay be used to determine the probability of prostate cancer on biopsy in individual men. Family and patient history can be used in combination with Beckman Coulterphiresults to determine the best individualized patient management decisions.In addition to the sensitivity and specificity analyses of the multi-site study data, we estimated an individual's probability of having detectable cancer based on the Beckman Coulterphivalues. In a population of men with PSA in the 4.0 to 10.0 ng/mL range and a non-suspicious DRE, a 25 percent positive biopsy rate has been previously reported.6,25The multi-site study population consisted of approximately 49.2 percent (324/658) cancer subjects and 50.8 percent (334/658) non-cancer subjects.Cancer probabilities based on the 49.2 percent proportion of cancer subjects would inflate the probability estimates for detecting cancer. Therefore, the proportion of cancer subjects was adjusted to 25 percent prior to calculating cancer probabilities for various Beckman Coulterphiscores. This adjustment provides accurate probabilities for the group of men in whom this test will be used. The bootstrap method was used to repetitively sample the multi-site study population.26Each sampling consisted of 334 (75 percent) benign subjects and 111 (25 percent) cancer subjects, for a total of 445 subjects. This random sampling process was repeated 1,000 times. We calculated mean cancer probabilities on biopsy and nonparametric 95 percent confidence intervals (2.5th and 97.5th percentiles). This repetitive sampling method increases the reliability of the probability of prostate cancer on biopsy estimates.Higher Beckman Coulterphivalues are associated with higher probability of prostate cancer.3Interpretation of Beckman CoulterphiBeckman Coulterphiis anin vitroDiagnostic Multivariate Index Assay (IVDMIA) used in combination with the Access Hybritech PSA, free PSA, and p2PSA assays designed to optimize specificity relative to %fPSA and PSA to determine the probability of prostate cancer on biopsy.3Beckman Coulterphihas been shown to significantly improve clinical specificity across the range of clinical sensitivity and cancer detection relative to PSA (p-value <0.001) and %fPSA (p-value = 0.009) in the PSA range of 4 to 10 ng/mL, in men ≥50 years of age with non-suspicious DRE.The selection of an appropriate Beckman Coulterphiscore that guides patient management considers the percentage of cancers detected (clinical sensitivity), and the percentage of men without cancer, in whom biopsy may be avoided (clinical specificity). For example, using the Hybritech calibration for PSA and free PSA, a Beckman Coulterphivalue of 22.1 corresponds to 95 percent sensitivity and 14.1 percent clinical specificity. Therefore, approximately one in seven men may avoid prostate biopsy while detecting 95 percent of cancers if their Beckman Coulterphivalue is less than 22.1.A Beckman Coulterphivalue of 27.0 corresponds to 90 percent clinical sensitivity and 31.1 percent clinical specificity. Therefore, nearly one in three men may avoid prostate biopsy while detecting 90 percent of cancers if their Beckman Coulterphivalue is less than 27.0.A Beckman Coulterphivalue of 31.3 corresponds to 80 percent clinical sensitivity and 46.1 percent clinical specificity. Therefore, approximately one in two men may avoid prostate biopsy while detecting 80 percent of cancers if their Beckman Coulterphivalue is less than 31.3. For men with a Beckman Coulterphivalue above the cutoff, the probability of prostate cancer on biopsy of cancer increases and may affect the clinical management of each patient.Low Beckman Coulterphiscores are associated with a lower probability of prostate cancer on biopsy, and higher scores are associated with an increased probability of prostate cancer on biopsy. The choice of an appropriate Beckman Coulterphiscore to be used in guiding clinical decision-making may vary for each patient and may depend in part on other clinically important factors or on family history of disease.

Men's Health, Cancer Screening

Offered as part of multiple lab tests

Hormone Testing, Men's Health

This immunoassay is intended for the in vitro quantitative determination of testosterone in human serum and plasma.Testosterone is the principal androgen in men.3,4The production of testosterone by the male testes isstimulatedby luteinizing hormone (LH), which is produced by the pituitary. LH secretion is, in turn, inhibited through a negative feedback loop by increased concentrations of testosterone and its metabolites. Most of the testosterone in males is produced by the Leydig cells of the testes and is secreted into the seminiferous tubule, where it is complexed to a protein made by the Sertoli cells. This results in the high local levels of testosterone that are required for normal sperm production.Diminished testosterone production is one of many potential causes of infertility in males.4,5Low testosterone concentrations can be caused by testicular failure (primary hypogonadism) or inadequate stimulation by pituitary gonadotropins (secondary hypogonadism). Since men with hypogonadism often have high SHBG levels, the measurement of free or bioavailable testosterone has been advocated when total testosterone levels are normal in men with symptoms of androgen deficiency.6Significant physiological changes occur in men as they age, in part due to a gradual decline in testosterone levels.7,8It is generally accepted that the principal cause of this age-related decrease in testosterone production is testicular failure, although diminished gonadotropin production may play a role.6By 75 years of age, the average male testosterone drops to 65% of average level in young adults. “Andropause” is a term that has been used to refer to the constellation of symptoms associated with the age-related decline in testosterone production in men.6,9The adult male reference range for testosterone was established by Travison and coworkers through an epidemiologic study that included men from different geographic regions of the United States and Europe.2Testosterone measurment was harmonized to the Center for Disease Control reference method.2The reference population included only men younger than 40 years of age who had a BMI less than 30. Much smaller amounts of testosterone and dihydrotestosterone are produced in women than in men.3,4Weaker adrenal androgens and ovarian precursor molecules including androstenedione, DHEA, and DHEA sulfate can have significant androgenic effects in women. The ovary and adrenal glands produce some testosterone, but the majority of the testosterone in women is derived from the peripheral conversion of other steroids. Often, the first sign of testosterone excess in women is the development of male pattern hair growth, which is referred to as hirsutism.1,4,5,10It should be noted that some women experience hair growth similar to that caused by increased testosterone due to racial or genetic causes and not due to excessive androgens. Measurement of the testosterone may help to distinguish racial or genetic causes of hirsutism from the abnormal pathology, particularly in women with mixed ethnic backgrounds. Women with more excessive testosterone levels may also experience virilization, with symptoms including increased muscle mass, redistribution of body fat, enlargement of the clitoris, deepening of the voice, and acne and increased perspiration. These women can also suffer from androgenic alopecia, the female equivalent of male pattern baldness.Many women with slowly progressive androgenic symptoms are diagnosed as having polycystic ovary syndrome (PCOS).10-12PCOS is relatively common, affecting approximately 6% of women of reproductive age.7Women with this complex syndrome experience symptoms of androgen excess associated with menstrual abnormalities and infertility. Most women with the syndrome have polycystic ovaries that can be detected by ultrasonography, although this finding is not essential for diagnosis.4,5,13Chronic anovulation experienced by patients with PCOS increases their risk of developing endometrial cancer. Women with PCOS are often overweight and are likely to suffer from insulin resistance putting them at increased risk for developing type 2 diabetes mellitus.3,11Obesity and insulin resistance can result in acanthosis nigricans, a skin condition that is characterized by hyperpigmented, velvety plaques of body folds.3Lipid abnormalities, including decreased high-density lipoprotein cholesterol levels and elevated triglyceride levels as well as impaired fibrinolysis, are seen in women with PCOS.11Cardiovascular disease is more prevalent, and women with PCOS have a significantly increased risk for myocardial infarction.11

Men's Health, Cancer Screening

Offered as part of multiple lab tests

Men's Health, Hormone Testing

Testosterone circulates almost entirely bound to transport proteins: Normally less than 1-2% is free. The principal transport protein for testosterone is known as sex hormone binding globulin (SHBG) or testosterone-estradiol binding globulin (TeBG). Testosterone measurements are used to assess erectile dysfunction, infertility, gynecomastia, and osteoporosis and to assess hormone replacement therapy.

Men's Health, Cancer Screening

In general, serum PSA levels increase due to physical changes to prostate architecture caused by trauma, infection, inflammation, prostate manipulation, benign prostatic hypertrophy (BPH), or malignancy.3,4The sensitivity of PSA levels to these changes serves as the basis for the clinical use of the test. The PSA concentration in the serum of healthy men is a millionfold lower than that in seminal fluid. PSA in seminal fluid is predominantly free or uncomplexed. In serum, the majority of PSA is bound to inhibitors, including α1-antichymotrypsin (ACT) and α2-macroglobulin (A2M). Measured total PSA consists of free and ACT-bound, since PSA complexed to A2M is not immunologically detectable.Catalona and coworkers found that one in four patients with normal DRE and PSA levels between 4.0 and 10.0 ng/mL have prostate cancer.2They recommend using a cutoff of 25% free PSA for this group of men (see Limitations) to identify individuals with an increased risk of prostate cancer. They found that 95% of men with cancer (as determined by biopsy) with normal DRE and total PSA between 4.0 and 10.0 ng/mL had percent free PSA of ≤25%. Their study further indicated that 20% of men with benign disease (as determined by biopsy) with normal DRE and a total PSA between 4.0 and 10.0 ng/mL had percent free PSA greater than the 25% cutoff.Alternatively, percent free PSA may be used to determine the relative risk of prostate cancer in individual men.2The following table lists the probability of prostate cancer for men with nonsuspicious DRE results and total PSA between 4.0 and 10.0 ng/mL, by patient age (see Limitations). See table.% Free PSA50 to 64 Years65 to 75 Years0.00−10.0056%55%10.01−15.0024%35%15.01−20.0017%23%20.01−25.0010%20%>255%9%

Cancer Screening, Men's Health

Elevated serum PSA concentrations have been reported in men with prostate cancer, benign prostatic hypertrophy, and inflammatory conditions of the prostate.

Men's Health, Pregnancy & Fertility

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Men's Health, Pregnancy & Fertility

Offered as part of multiple lab tests

Men's Health

The concentration of free testosterone is very low, typically <2% of the total testosterone concentration. In most men and women, >50% of total circulating testosterone is bound to sex hormone-binding globulin (SHBG) and most of the rest is bound to albumin.1Routinely available assay methods used to measure total testosterone are not sensitive enough to quantitate accurately the free testosterone fraction directly. Free testosterone is estimated in this profile by an indirect method, equilibrium ultrafiltration. Tritiated testosterone is added to the sample and allowed to come to equilibrium with testosterone in the serum at physiological temperature.2,3The amount of the added radiolabeled testosterone must be low enough to ensure that the addition will not significantly increase the total testosterone concentration. Once equilibrium is achieved, the free testosterone is separated from the bound testosterone by filtration through a membrane by centrifugal ultrafiltration.4The radioactivity of the protein-free ultrafiltrate is measured and used to calculate the percent free testosterone. The concentration of free testosterone is then calculated by multiplying the percent free testosterone by the total testosterone concentration.

Hormone Testing, Men's Health

Helpful in assessing testicular function in male and managing hirsutism, virilization in females.

Hormone Testing, Men's Health

Helpful in assessing testicular function in prepubescent hypogonadal males and in managing hirsutism, virilization in females.

Men's Health

Prostatic acid phosphatase has been used as a tumor marker ever since the observation by Gutman in 19381that elevated levels of this enzyme are found in patients with metastatic prostate cancer. PAP determination in conjunction with PSA measurements is useful in assessing the prognosis of prostate cancer.2Measurement of two markers allows identification of prostate cancer patients who have an elevation of PAP but not of PSA, and thus help monitoring the course of disease and response to treatment. PAP is more specific than PSA and less false-positives are seen due to benign prostatic hyperplasia.

Cancer Screening, Men's Health

High concentrations of acid phosphatase are found in the prostate gland. Significant amounts are also found in platelets, bone, spleen, kidney and liver. Prostatic Acid Phosphatase (PAP) is a component of total acid phosphates and is a major constituent in seminal fluid and is also secreted in the urine. PAP is normally found in serum in very low levels.PAP measurement has found clinical application in the management of prostatic cancer patients. Serum PAP measurements have been useful in monitoring remission or relapse of a prostatic malignancy and in assessing the effectiveness of various treatment regimes. Thus, normalization in serum PAP levels has been observed following successful therapeutic intervention, while recurrent or residual disease has been associated with elevated levels of PAP.

Cancer Screening, Men's Health

In men over 50 years with total PSA between 4.0 and 10.0 ng/mL, the percent (%) free PSA gives an estimate of the probability of cancer. In these circumstances the measurement of the % free PSA may aid in avoiding unnecessary biopsies.Elevated levels of Prostate Specific Antigen (PSA) have been associated with benign and malignant prostatic disorders. Studies indicate that in men 50 years or older measurement of PSA is a useful addition to the digital rectal exam in the early detection of prostate cancer. In addition, PSA decreases to undetectable levels following complete resection of the tumor and may rise again with recurrent disease or persist with residual disease. Thus, PSA levels may be of assistance in the management of prostate cancer patients.

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Hormone Testing, Men's Health

DHT is a potent androgen derived from testosterone via 5-Alpha-Reductase activity. 5-Alpha-Reductase deficiency results in incompletely virilized males (phenotypic females). This diagnosis is supported by an elevated ratio of testosterone to DHT.

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Men's Health, Cancer Screening

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Helpful in assessing testicular function in males and managing hirsutism, virilization in females.

Men's Health

AMH/MIS may be used in the detection of the onset of puberty in males, in the differential diagnosis of intersex disorders, cryptorchidism, or anorchidism and in the evaluation of male gonadal function in all ages.

Men's Health, Pregnancy & Fertility

Offered as part of multiple lab tests

Cancer Screening, Men's Health

For post-prostatectomy patients.The lower limit of accurate quantification for this assay is 0.02 ng/mL. PSA values less than 0.02 ng/mL cannot be accurately measured and will be reported as less than 0.02 ng/mL. Specimens with PSA levels below the lower limit of accurate quantification should be considered as negative. In patients with a negative result for post-prostatectomy PSA, serial monitoring of PSA levels at regular intervals, along with physical examinations and other tests, may help to detect recurrent prostate cancer.

Cancer Screening, Men's Health

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Men's Health, Pregnancy & Fertility

Offered as part of multiple lab tests

Men's Health

Measurement of 3a-androstanediol glucuronide (3ADG) is used in patients with hirsutism of either the idiopathic type or secondary to polycystic ovarian syndrome (PCOS).

Hormone Testing, Men's Health

Offered as part of multiple lab tests

Hormone Testing, Men's Health

Offered as part of multiple lab tests