The differential diagnosis for Washington’s infertility includes conditions from each of the six major categories of male infertility (Table 1). Could Washington have had Klinefelter’s syndrome or another cause of germ-cell failure? Klinefelter’s syndrome is typified by tall stature, testicular failure, and mild to severe cognitive deficits, especially in terms of visualospatial and language abilities (8). Klinefelter’s syndrome could explain Washington’s remarkable height. Washington was extremely tall—probably more than 6 feet 3 inches (9, p. 34)—a veritable giant for his age; however, tall stature was a family trait. A diagnosis of Klinefelter’s syndrome would also provide an explanation for his well-documented dental woes, because many individuals with Klinefelter’s syndrome suffer from taurodontism, a genetic enlargement of the tooth pulp, which predisposes to premature dental caries (10).
Arguing against Klinefelter’s syndrome are contemporary descriptions of Washington as powerfully muscled and as a superb horseman, certainly not consistent with hypogonadism and visuospatial dysfunction. In addition, Washington’s speeches and surviving writings demonstrate a superior facility with language, making Klinefelter’s syndrome seem very unlikely. It is possible that Washington could have had a genetic cause of infertility, such as microdeletions in the Y chromosome, which are thought to cause approximately 7% of all male factor infertility (11).
Could Washington have had endocrine dysfunction, such as testosterone or gonadotropin deficiency? Congenital gonadotropin deficiency, or Kallmann’s syndrome, could have resulted in Washington’s tall height; however, there is no evidence that he suffered from severe testosterone deficiency. In fact, stories abound testifying to his great strength and vigor. As a child, he was noted to be an enthusiastic and superior athlete, running, wrestling, and horseback riding with great skill. In 1760, his adjutant, George Mercer, described him as possessed of:
. . .well-developed muscles indicating great strength. His bones and joints are large as are his hands and feet . . . . His mouth discloses some defective teeth . . . . His movements and gestures are graceful, his walk majestic and he is a splendid horseman (12, p. 191)
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Also arguing against endocrine dysfunction is an absence of difficulties with peripheral vision, osteoporosis, gynecomastia, pronounced fatigue, or depression. Therefore, endocrine dysfunction seems an unlikely cause of infertility for Washington.
Could Washington’s infertility have been due to congenital anatomic causes, such as cryptorchidism, absence of the vas deferens, or a varicocele? Congenital absence of the vas deferens can occur either spontaneously or in association with certain diseases, such as cystic fibrosis. Washington clearly did not have cystic fibrosis, but a spontaneous absence of the vas is possible, if rare. Because either cryptorchidism or a varicocele would likely have a greater impact on sperm production than testosterone secretion, either could explain Washington’s infertility; however, unless severe, these conditions cause infertility infrequently (13, 14).
Could Washington have had sexual dysfunction? Retrograde ejaculation is unlikely in the absence of spinal cord trauma, neuropathy, or urologic surgery. Erectile dysfunction due to diabetes or vascular disease seems implausible in such a healthy, vigorous man. Inadequate sexual frequency is theoretically possible but unlikely because Washington’s relationship with Martha was intimate, and as a farmer and expert mule breeder he was certainly well aware of the necessary means!
Could Washington’s infertility have been due to toxic exposures? It is interesting to note that Washington used calomel (mercurous chloride) extensively during his early 20s for treatment of his chronic bloody diarrhea and abdominal pain (see below). Although mercury exposure has been shown to lead to a decrease in sperm counts in higher mammals (15), this effect is usually transient and is an unlikely cause of long-term infertility.
Male infertility can be caused by infections of the testis, epididymis, or prostate caused by mumps, sexually transmitted disease (e.g., gonorrhea or chlamydia), or tuberculosis. As was the case for most individuals in the 18th century, Washington had an impressive variety of illnesses during his life, including mumps. However, orchitis in association with mumps infection does not occur before puberty (16), making mumps an unlikely cause of infertility in Washington, who had mumps during early childhood (9, p. 34). A sexually transmitted disease seems unlikely in Washington’s case, given his character and strong sense of moral propriety.
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The one infection that Washington likely contracted that might explain his infertility is tuberculosis. During Washington’s life, tuberculosis was very common and frequently lethal. One historian has estimated that one quarter of all adult deaths in Europe at the time were due to tuberculosis (17). In those who did not succumb initially, the infection was frequently life-long, and extrapulmonary manifestations were common.
Washington’s likely exposure to tuberculosis was via his brother Lawrence, who was dying of the disease when George accompanied him to Barbados in 1751 at age 19. While in Barbados, Washington contracted smallpox and was very ill (9, p. 61), a circumstance that would have weakened his immunity considerably. On his return from Barbados, Washington spent several months combating pleurisy. Given the timing and duration of this illness, it was quite probably an initial pulmonary infection with tuberculosis, contracted from his brother. Shortly after Washington’s recovery from pleurisy, Lawrence died from tuberculosis (18, p. 263).
George spent much of the next several years fighting with the English against the French during the French and Indian War. During this period, he was troubled with repeated attacks of bloody diarrhea, abdominal pain, and fever (9, pp. 132, 165–70). These recurrent episodes of bloody diarrhea over years are inconsistent with bacterial dysentery (19) or inflammatory bowel disease and given his likely pulmonary infection with tuberculosis probably represented enteric tuberculosis. Upwards of 70% of individuals with untreated pulmonary tuberculosis will develop gastrointestinal tuberculosis from swallowing the highly infectious pulmonary secretions (20). Such individuals are frequently symptomatic, with fever, bloody diarrhea, and abdominal pain (21).
It is interesting to note that Washington himself feared that he might have tuberculosis, the disease he had seen slowly kill his older brother. By November 1757 Washington was so feeble that he could barely walk and was warned by a local doctor that he was exhibiting signs of “decay”—the term for tuberculosis (9, p. 170). In late 1757 he wrote:
My disorder at times returns obstinately upon me in spite of the efforts of all the sons of Aesculapius. At certain times, I have been reduced to great extremity. . . . My constitution is certainly greatly impaired (and) nothing can retrieve my health but the greatest care. . . . (9, p. 169)
Fortunately, Washington recovered before meeting Martha and was never again troubled with abdominal pain. It seems possible, however, that before his marriage to Martha he developed genitourinary tuberculosis in addition to his likely gastrointestinal infection. Classic studies of soldiers with tuberculous pleurisy during World War II demonstrated that two thirds developed chronic organ tuberculosis within 5 years of their initial infection (22). Infection of the epididymitis or testes is seen in 20% of these individuals and frequently results in infertility (23, 24).
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Given the absence of evidence for another source of Washington’s infertility and his exposure to and symptoms of tuberculosis, I propose that the most likely cause of George Washington’s infertility was tuberculous epididymitis. However, I cannot rule out idiopathic causes of germcell failure, such as microdeletions in the Y chromosome, or anatomic abnormalities, such as congenital absence of the vas deferens, varicocele, or cryptorchidism as potential causes of Washington’s infertility.
How would one approach the diagnosis of Washington’s infertility today? A work-up would begin with a history and physical examination and a seminal fluid analysis. If sperm were absent, imaging of the vas deferens and ejaculatory duct would be performed to distinguish between failure of sperm production and obstruction. If abnormalities on testicular examination were noted, a testicular ultrasound would be indicated. Tuberculous infection of the epididymitis can lead to massive dilatation of the organ (25), and aspiration of epididymal contents for culture could be performed. If tuberculosis were diagnosed, treatment with isoniazid and rifampin for 9 months would be recommended; however, this therapy would be unlikely to reverse obstructive azoospermia, given the scarring of the epididymis resulting from the infection (26).
Treatment of Washington’s infertility would vary depending on whether sperm were present in an ejaculated semen specimen. If present, sperm could be used in intrauterine insemination, IVF, or intracytoplasmic sperm injection (ICSI). If sperm were absent from an ejaculated specimen, testicular biopsy or aspiration could be performed to attempt sperm retrieval. If sperm were isolated from the testicular biopsy, ICSI could be performed (27). Intracytoplasmic sperm injection has been used successfully to treat obstructive azoospermia secondary to tuberculous epididymitis with a success rate of greater than 50% (28).
WASHINGTON’S INFERTILITY: HISTORICAL IMPACT
One wonders about the impact of Washington’s infertility on the course of history. Most tempting is to speculate as to whether his lack of an heir impacted on his willingness to return power to the relatively weak Congress at the end of the Revolutionary War. At the war’s conclusion he easily could have contemplated becoming a military dictator or even installing himself as king. Indeed, many on his own general staff urged him to do so (9, p. 403). To his credit, however, Washington resigned his commission and returned to his Virginia farm. This act, wherein the leader of a successful military revolution voluntarily returns power to a civil authority is almost unique in history and is one of the reasons Washington was so revered by his contemporaries and eventually unanimously selected to become the nation’s first president 5 years later in 1788.
A more likely effect of Washington’s infertility was that he tended to nurture promising young men to whom he was not related. Most prominent of these was his favorite, the Marquis de Lafayette, a distant cousin of Louis XVI. After spending 2 years as an aide-de-camp to Washington, Lafayette returned to France and was instrumental in convincing King Louis to have France enter the war on the side of the revolutionaries (9, p. 398)—an intervention that was ultimately to decide the war in favor of the colonies.
It is surprising how little the topic of Washington’s infertility is discussed among historians and the medical community. A literature search identified only one medical article speculating as to the cause of Washington’s infertility (29). This omission is likely due in part to the frequent erroneous assumption that infertility is mostly female in origin. Additionally, there might be reluctance on the part of biographers to discuss Washington’s infertility because they fear that discussion of his infertility would diminish him in some way. This, of course, belies the fact that male infertility mostly occurs independent of one’s other characteristics and affects the great and the humble without regard to historical stature.
Despite great successes in his military and civilian life and his central role in the creation of the world’s most enduring democratic nation, George Washington likely suffered from male infertility and harbored great personal sadness about his inability to father an heir. In my opinion, it seems most likely that his infertility was due to one of history’s greatest killers, tuberculosis, which were he alive today could be well treated with medication; furthermore, techniques in assisted reproduction, such as ICSI, could be attempted to address his and Martha’s infertility.
culled from www.asrm.org
Acknowledgments: The author thanks William J. Bremner, M.D., Ph.D., and Alvin M. Matsumoto, M.D., from the University of Washington Departments of Medicine, and Richard Berger, M.D., from the University of Washington Department of Urology for helpful comments and review of the manuscript.
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