In a small remote village known as Las Salinas in the Dominican Republic, a number of children are born with a peculiar condition, and what makes it more peculiar is its high incidence. These children from this isolated village are born female but their sex changes as they grow up. They grow penises at puberty when they start to become boys. The village has attracted the attention of endocrinologist Dr. Julianne Imperato-McGinley who went there to investigate the case during the 1970s. These children are called “guevedoces” and their transformation is celebrated among the locals.

The word guevedoce is derived from a slang Spanish phrase “huevo/guevo a los doce” and literally translates to “balls/penis at twelve”, twelve being the age at which these children transform into males. 

During the first few weeks of the fetus development, a baby is neither male nor female. But after eight weeks, the sex hormones come into play and if the baby carries XY chromosomes, the gonads become testicles and testosterone is released into a structure known as tubercle. The testosterone is then transformed into dihydro-testosterone, which in turn transforms the tubercle into a penis. And, if the baby carries XX chromosomes, then no dihydro-testosterone is created and so the tubercle becomes a clitoris. However, in the case of guevedoces, though the children posses Y-chromosome and have male internal organs, they appear female externally at birth and are raised as girls.

Dr. Julianne Imperato-McGinley, who was researching guevedoces, discovered that the reason these children were born female despite having XY chromosome was because they are deficient in an enzyme known as 5-alpha-reductase.

The aforementioned conversion of testosterone to dihydro-testosterone is done by an enzyme known as 5-alpha-reductase, which is absent among the guevedoces. The genetic mutation that causes the deficiency was passed down through generations and among themselves. 12 families out of 13 have at least one or more male who carries the mutation. However, being carriers doesn’t necessarily mean all of them are affected. On an average, 1 out of 90 males is an affected carrier, and the rest are either not carriers or not affected.

When puberty sets in, the children get a second surge of testosterone to which the body responds and it changes their external anatomy into male. 

Considering the number of children who are guevedoces, their transformation is seen as a common occurrence and is not seen as a cause for concern among villagers. They even celebrate the natural transformation of the child who was believed to be a girl into a boy and the child assumes a male role in the society. In many cases, though the child is brought up as a girl, the gender identity has always been male.

The high prevalence of 5-alpha-reductase deficiency in Las Salinas is thought to be because of “founder effect” or “bottleneck effect”, with the villagers being interrelated because they are geographically isolated and descending from an individual who carried the genetic mutation. 

The “founder effect” is the lack of genetic variation among the population of a newly established, isolated or closed human settlement or community because of inbreeding. The “bottleneck effect” is the lack of genetic variation because of a sudden decrease in population due to natural disasters or genocide, leaving only the survivors to continue through next generations. The comparatively large number of people with 5-alpha-reductase deficiency could have been because of either of these two reasons along with their isolation geographically.

In 1974, Dr. Imperato-McGinley made an observation that guevedoces have small prostates, which led to the development of finasteride, a drug prescribed for benign enlargement of prostate and pattern baldness among men. 

The observation was picked up by Roy Vagelos, the head of research at a multinational pharmaceutical giant, Merck. He began the research which led to the development of finasteride, a drug that can mimic the 5-alpha-reductase deficiency seen in guevedoces. The drug is prescribed to old men who suffer from benign enlargement of prostates.

[sources: bbc.com, wikipedia]