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JU INSIGHT Positive Predictive Value of Follicle Stimulating Hormone Levels Among Nonazoospermic Men

By: Solomon Hayon, MD; Northwestern University Feinberg School of Medicine, Chicago, Illinois; Medical University of South Carolina, Charleston, Sai Kaushik SR Kuma, MS; Northwestern University Feinberg School of Medicine, Chicago, Illinois, Daniel Greenberg, MD; Northwestern University Feinberg School of Medicine, Chicago, Illinois, Xinlei Mi, PhD; Northwestern University Feinberg School of Medicine, Chicago, Illinois, Richard J. Fantus, MD; University of Kansas Medical Center, Kansas City, Robert E. Brannigan, MD; Northwestern University Feinberg School of Medicine, Chicago, Illinois, Joshua A. Halpern, MD, MS; Northwestern University Feinberg School of Medicine, Chicago, Illinois; Posterity Health, Centennial, Colorado | Posted on: 17 Jul 2024

Hayon S, Kumar SKS, Greenberg D, et al. Distribution and positive predictive value of follicle stimulating hormone levels among nonazoospermic men. J Urol. 2024;212(1):145-152. doi:10.1097/JU.0000000000003957

Study Need and Importance

Follicle stimulating hormone (FSH) levels are commonly ordered during male fertility evaluation. Reported normal values are variable, and prior studies have shown that FSH (along with testicular size) has diagnostic value in determining the etiology of azoospermia. However, literature regarding the utility of FSH in predicting the fertility potential of nonazoospermic men is limited.

What We Found

In a study of over 1300 men, we found that median FSH levels were lower in men with a total motile sperm count (TMSC) of > 20 million (fertile), as compared to men with a TMSC of < 20 million (subfertile). There was a wide distribution FSH values within each group, and the positive predictive values of FSH for subfertility were < 60% for FSH values ranging from 2.2 to 9.3. PPV of FSH did improve toward the higher end of the distribution, but it was not until the 95th percentile value (12.1) that positive predictive value of over 70% was reached (Table).

Table. Follicle Stimulating Hormone Percentiles in Nonazoospermic Men With Optimism Corrected Area Under the Curve Values and Mean Positive Predictive Values for Subfertility Status Based on Total Motile Sperm Count

FSH percentile FSH threshold, mIU/mL Optimism-corrected AUC Mean PPV
5th 1.8 0.57 0.43
10th 2.2 0.57 0.51
25th 2.9 0.61 0.58
50th 4.3 0.67 0.49
75th 6.2 0.67 0.48
90th 9.3 0.66 0.59
95th 12.1 0.64 0.73
99th 20.8 0.58 0.84
Abbreviations: AUC, area under the curve; FSH, follicle stimulating hormone; PPV, positive predictive value.
Subfertility was defined as total motile sperm count < 20 million on 2 semen analyses.

Limitations

This was a retrospective study, and important clinical variables such as testis size and pregnancy rates were not included. However, this is the largest dataset evaluating FSH in nonazoospermic men classified by TMSC.

Interpretation for Patient Care

FSH can provide diagnostic value in the workup of nonazoospermic patients; however, its clinical applicability is limited to values at the extreme ends of the distribution. The search for a more reliable serum marker of fertility potential continues, but this manuscript sheds light on how to interpret FSH testing in nonazoospermic men.

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