Reiner & Gearhart's NEJM Study on Cloacal Exstrophy - Review by Vernon Rosario, M.D., Ph.D.

Classification: Recent Publications

The following review comes from Vernon A. Rosario, M.D., Ph.D., former Chair of ISNA's Medical Advisory Board.

REVIEW BY VERNON ROSARIO:

Long-time ISNA friend and supporter Dr. William G. Reiner recently published a groundbreaking article with Dr. John P. Gearhart that gives further evidentiary support to ISNA’s mission. The article, “Discordant Sexual Identity in Some Genetic Males with Cloacal Exstrophy Assigned to Female Sex at Birth” was published in the prestigious New England Journal of Medicine (vol. 350, Jan. 22, 2004). They described a long-term follow-up study of a group of 16 chromosomally male (XY) individuals born with cloacal exstrophy. This is a rare birth defect affecting 1 in 400,000 live births—slightly more common in males then females. It is an anatomical defect beginning early in embryonic development and the most severe manifestation in the spectrum of exstrophy-epispadias (congenital anomalies of the bladder, genitals, and pelvis). The abdomen is not closed, thus exposing the gastrointestinal tract and urinary bladder. Frequently the intestine is shortened and malformed with the bladder. The anus may also not be open. In females, the clitoris may be split and there can be two vaginal openings. In males, the penis is short and flat, split in two, or entirely absent. It is frequently associated with abnormal kidney and spinal development (spina bifida, scoliosis, meningocele). The cause is unknown and there is no known means of prevention.

At birth, these infants require emergency treatment. Once medically stabilized, the spinal, gastrointestinal, bladder defects are corrected or alleviated so that urinary and fecal continence can often be achieved. There may be persistent neurological deficits.

In the past 25 years, the trend had been to surgically reassign males with cloacal exstrophy as females by removing the testes and constructing labia. This followed from John Money’s work with intersexed children, and his conviction that infants with a very short or ambiguous penis could be reassigned female and develop a normal female gender identity. This notion, which served as the cornerstone for neonatal sex reassignment in a variety of intersex conditions, has increasingly been questioned in the past decade. Reiner and Gearhart’s findings further undermine the rationale for sex-reassignment in the case of cloacal exstrophy.

Of their 16 affected subjects, 14 had been reassigned female at birth. At follow-up, between ages 5 to 12, 8 of those reassigned female now identified as boys. The children and their parents completed a battery of questionnaires assessing psychosexual development, sexual identity, and gendered behavior. Follow-up assessments were done at least annually ranging from 34 to 98 months follow-up. All of the subject had moderate-to-marked male-typical attitudes and interests. The two children reared as males continued to identify as males. Of the 14 reassigned female at birth, five still persistently identified as girls, four spontaneously declared a male identity, and four chose to identify as boys after told that they were born male. Reiner and Gearhart note, in passing, that none of their genetically female patients with cloacal exstrophy demonstrated atypical gendered behavior or gender uncertainty.

Reiner and Gearhart conclude that female sex assignment of males born with cloacal exstrophy does not always result in female gender identification (indeed not even half the time) and never results in unambiguously female behavior. Their results cast strong doubts on the practice of female sex reassignment in this condition. More speculatively, they suggest that male gender identity and gender role may be hardwired into the brain in these cases since XY males with cloacal exstrophy have normally functioning testes would have exerted the usual masculinizing influence on the developing brain.

The researchers note that cloacal exstrophy is not an intersex condition in the sense that it is not the result (as far as we know) of an anomaly of the sex chromosomes, sex-determining genes, or sex hormones. In cloacal exstrophy, the genitals are seriously malformed and often urogenital surgery must be performed to improve urinary and fecal passage. Reiner and Gearhart’s findings suggest that corrective surgeries should be done without sex reassignment, in particular removal of the testes. These boys would still be left with atypical genitals, and the authors believe they would probably want a penile reconstruction for sexual functioning. Their results, therefore, strongly support ISNA’s contention that sex determination should be based on a thorough diagnostic evaluation, that only life-saving genital surgeries be performed, and that genital plastic surgeries be deferred until the individual can participate in medical decision making. We applaud Reiner and Gearhart for furthering our knowledge base and their reliance on long-term follow-ups of the subjects themselves. We hope other researchers will help further our understanding of intersex conditions and their optimal treatment.

Reiner, W. G. and J. P. Gearhart (2004). "Discordant sexual identity in some genetic males with cloacal exstrophy assigned to female sex at birth." New England Journal of Medicine 350(4): 333-41.