An Evaluation of Reported Follicle-stimulating Hormone, Luteinizing Hormone, Estradiol, and Prolactin Reference Ranges in the United States.

OBJECTIVE: To characterize US clinical laboratory reference range reporting and testing methods of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and prolactin. METHODS: One hundred and seventeen US laboratories were surveyed. Outcomes measured were variation in lower and upper limits of normal male reference ranges for serum FSH, LH, estradiol, and prolactin, method of analysis and source of reference range RESULTS: The upper limit of normal reference ranges for FSH, LH, estradiol, and prolactin varied substantially across laboratories compared to the lower limits. The range of upper limits of FSH, LH, estradiol, and prolactin respectively are 7.9-20.0, 4.9-86.5, 37.7-77.0, and 7.4-25.0. Ninety-four percent of laboratories performed measurements on in-house high throughput analyzer utilizing immunoassays. Seventy percent of reported reference ranges for each hormone were based on validation studies of the analyzer's package insert values. Ten percent of laboratories derived their own reference ranges. Both the validation studies and derivations were based on a limited number of patient samples, ranging from 20 to 200. CONCLUSION: Current reference ranges are based on small population studies of men with unknown medical histories, sexual or reproductive function. Influence of race and age has not been evaluated and could potentially be important in normal variation. The absence of standard information has yielded a spectrum of upper and lower normal values, which could delay an appropriate male infertility evaluation. Our findings highlight the need for a large population study of males with known normal sexual and reproductive function to formulate more accurate clinical reference ranges.

Current Practices of Measuring and Reference Range Reporting of Free and Total Testosterone in the United States.

PURPOSE: The evaluation and management of male hypogonadism should be based on symptoms and on serum testosterone levels. Diagnostically this relies on accurate testing and reference values. Our objective was to define the distribution of reference values and assays for free and total testosterone by clinical laboratories in the United States. MATERIALS AND METHODS: Upper and lower reference values, assay methodology and source of published reference ranges were obtained from laboratories across the country. A standardized survey was reviewed with laboratory staff via telephone. Descriptive statistics were used to tabulate results. RESULTS: We surveyed a total of 120 laboratories in 47 states. Total testosterone was measured in house at 73% of laboratories. At the remaining laboratories studies were sent to larger centralized reference facilities. The mean ± SD lower reference value of total testosterone was 231 ± 46 ng/dl (range 160 to 300) and the mean upper limit was 850 ± 141 ng/dl (range 726 to 1,130). Only 9% of laboratories where in-house total testosterone testing was performed created a reference range unique to their region. Others validated the instrument recommended reference values in a small number of internal test samples. For free testosterone 82% of laboratories sent testing to larger centralized reference laboratories where equilibrium dialysis and/or liquid chromatography with mass spectrometry was done. The remaining laboratories used published algorithms to calculate serum free testosterone. CONCLUSIONS: Reference ranges for testosterone assays vary significantly among laboratories. The ranges are predominantly defined by limited population studies of men with unknown medical and reproductive histories. These poorly defined and variable reference values, especially the lower limit, affect how clinicians determine treatment.