Absence of prostatic growth in large cohort of adult female patients with congenital adrenal hyperplasia, "Beyond the Abstract," by Ariella A. Friedman, MD

BERKELEY, CA (UroToday.com) - The idea for this study came about due to a report of prostate cancer in an adult 46,XX patient with markedly virilizing congenital adrenal hyperplasia (CAH )and elevated androgens.[1] In our study, 11 adult female patients with congenital adrenal hyperplasia were longitudinally followed into adulthood and assessed for the presence of prostatic growth. When we looked at these 11 adult women, 5 of whom had elevated testosterone (95-960) and one of whom had elevated DHT (52), none had visible prostatic growth on MRI. This was despite evidence of genital virilization in all, radiographically, and a virilized appearance in 9 of 11, clinically. Interestingly, one patient did have a PSA of 0.2 (the woman with a T of 960 and a DHT of 52). We were surprised by these findings, especially because of a similar study (although with slightly different methodology) that detected PSA in 10% of teenage girls with virilizing CAH.[2]

Our understanding of the relationship between androgens, prostatic growth, and prostatic neoplasia is evolving. Utilizing immunohistochemical techniques and 3-D remodeling, Dietrich, et al., have described the Skene’s glands not as the discrete, solid structure we identify with the prostate but rather, a network of glands surrounding the urethra, with varying degrees of confluence. These periurethral glands stain positive for PSA, PSAP, and androgen receptors.[3] These findings invoke the idea that Skene’s glands and the prostate exist on a continuum of graded virilization. Similar anatomic depictions and conceptualizations of the Skene’s glands have been around for decades (Figures 1 and 2). However, characterization as the “female prostate” is only part of the story and perhaps misleading.

It may be attractive to associate varying Skene’s/prostatic morphology with degrees of virilization. Yet while it may then be tempting to extrapolate further that the androgen excess seen in CAH could contribute to prostatic neoplasia, one must be careful in drawing such parallels. Though androgens are known to fuel some prostatic adenocarcinomas (thus, the rationale for androgen deprivation therapy in prostate cancer), some prostate cancers are hormone refractory. Further, while it was previously thought that eunuchs, or severely hypogonadal men, did not get prostate cancer, recent innovative studies are challenging that conception. Abraham Morgentaler has demonstrated still-significant risks of prostate cancer in hypogonadal men[4] and has generated results that challenge the dogma that testosterone therapy is absolutely contraindicated in men with prostate cancer.[5] As we continue to expand our knowledge of androgens, the prostatic anlagen, and prostate cancer, as well as their complex interaction, we may hope to find many more lessons from one discipline of urology elucidated by another.

We were fortunate to have a population of adult female patients with CAH, who had been longitudinally followed from childhood. One of the challenges in managing complex pediatric patients as they advance into adulthood is the often fragmented way in which their care is transitioned from pediatric to adult specialists, combined with the lack of training by many adults in complex pediatric urology, as well as the paucity of data on patients for whom the academic priority had been on improved survival (at least beyond childhood) until very recently. Further complicating study of adult patients with disorders of sex development has been the marginalization of “intersex” into the outskirts of public conversation and prioritized academia. As the complex issues that many transitioning pediatric patients face upon entry into adulthood enter the consciousness of adult urologists, we will one day be better able to offer pediatric urology patients a more comprehensive framework for care as adults.

bta friedman fig1 thumb

bta friedman bta fig2 thumb
Figure 1: Huffman J.W.: Clinical significance of the paraurethral ducts and glands. Arch Surg; 1951; 62: 615-626 Figure 2: Huffman, J.W.: The detailed anatomy of the paraurethral ducts in the adult human female. Am J Obstet Gynecol, 1948; 55: 86-101

 

Special thanks to Dr. Abraham Morgentaler for his insights into the relationship between androgens and prostatic growth, as well as for sharing his correspondence with Dr. Haitel on her article in the Journal of Sexual Medicine.

References:

  1. Winters J, Chapman P, Powell D, et al. Female pseudohermaphroditism due to congenital adrenal hyperplasia complicated by adenocarcinoma of the prostate and clear cell carcinoma of the endometrium. Anat Pathol 1996; 106: 660.
  2. Paulino MCR, Steinmetz L, Filho HCM, et al. Pesquisa de tecido prostático em pacientes 46,XX portadoras da forma clássica de hiperplasia congênita das suprarrenais (Search of prostatic tissue in 46,XX congenital adrenal hyperplasia). Arq Bras Endocrinol Metabol 2009; 53: 716.
  3. Dietrich WD, Susani M, Stifter L, et al. The human female prostate – immunohistochemical study with prostate-specific antigen, prostate-specific alkaline phosphatas, and androgen receptor and 3-D modeling. J Sex Med, 2011; 8: 2816.
  4. Morgentaler A and Rhoden EL. Prevalence of prostate cancer among hypogonadal men with prostate-specific antigen levels of 4.0 ng/ml or less. Urology, 2006; 68: 1263.
  5. Morgentaler A, Lipshultz LI, Bennett R, et al. Testosterone therapy in men with untreated prostate cancer. J Urol, 2011; 195: 1256.

 

Written by:
Ariella A. Friedman, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

Children's Hospital of Michigan, 3901 Beaubien St., Clarks Building, 3rd Floor, Detroit, Michigan USA

Absence of prostatic growth in large cohort of adult female patients with congenital adrenal hyperplasia - Abstract

More Information about Beyond the Abstract

 

 

email news signup