The PCOS Plan. Jason FungЧитать онлайн книгу.
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The Diabetes of Bearded Women
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POLYCYSTIC OVARY SYNDROME (PCOS) has only been considered a disease in the last century, but it is actually an ancient disorder. Originally described as a gynecological curiosity, it is now the most common endocrine disorder of young women and is known to involve multiple organ systems.
EARLY DEFINITIONS
IN ANCIENT GREECE, the father of modern medicine, Hippocrates (460–377 BC), described “women whose menstruation is less than three days or is meagre, are robust, with a healthy complexion and a masculine appearance; yet they are not concerned about bearing children nor do they become pregnant.”1 This description of PCOS did not exist only in ancient Greece; it is found in ancient medical texts throughout the world.
The ancient Greek gynecologist Soranus of Ephesus (c. 98–138 AD) observed that “the majority of those [women] not menstruating are rather robust, like mannish and sterile women.” The renaissance French barber, surgeon, and obstetrician Ambroise Paré (1510–1590) noted that many infertile women with irregular menses are “stout, or manly women; therefore their voice is loud and bigge, like unto a mans, and they become bearded.” It’s quite an accurate description from a doctor who can apparently cut your hair, cut your leg off, or deliver your children. The Italian scientist Antonio Vallisneri (1661–1730) connected these masculinizing features and the abnormal shape of the ovaries into a single disease when he described several young, married infertile peasant women whose ovaries were shiny with a white surface and the size of pigeon eggs.2
In 1921 French doctors Émile Charles Achard and Joseph Thiers described a syndrome that included masculinizing features (acne, balding or receding hairline, excessive facial hair) and type 2 diabetes (which used to be called adult-onset diabetes). Further cases in 1928 cemented the link between what is now called PCOS and type 2 diabetes, and these were described in the classic article “Diabetes of Bearded Women.”3 Careful observation had already revealed to these astute clinicians a syndrome that included menstrual irregularities, infertility, masculine features, and obesity with its related type 2 diabetes. The only essential feature they missed from the modern definition of PCOS was the multiple cysts in the ovary, only because they lacked the ability to carry out simple, noninvasive imaging.
DETECTION AND DESCRIPTION IN THE MODERN ERA
DRS. IRVING STEIN and Michael Leventhal ushered in the modern era of PCOS in 1935 with their description of seven women with all the modern diagnostic features: masculinization, irregular menses, and polycystic ovaries.4 By making the connection between the lack of menstruation and the presence of enlarged ovaries, they achieved a breakthrough by merging these into a single syndrome: PCOS. The detection of enlarged cystic ovaries was difficult in the 1930s, and Stein and Leventhal achieved this either by direct surgical observation (laparotomy) or by using a now-defunct x-ray technique called pneumoroentgenography that involved making an incision in the abdomen to introduce air and then taking x-rays. The shadow of the enlarged ovary could be seen on the film. However, in an era before effective antibiotics, this procedure was a risky one.
Dr. Stein hypothesized that some as-yet-undetermined hormonal imbalance caused the ovaries to become cystic, and he suggested that surgically removing a wedge of the ovary might help to reverse the syndrome. And indeed, this crude surgery worked. All seven women began to menstruate again and two even got pregnant. With its main features defined, interest in PCOS surged, as reflected by the large increase in PCOS articles in the medical literature.
Figure 1.1. Number of publications on PCOS in the medical literature (MEDLINE)5
Subsequently, Drs. Stein and Leventhal performed ovarian wedge resection on another seventy-five women, restoring the menstrual cycles in 90 percent of cases and restoring fertility in 65 percent.6 Defining the syndrome and delineating a reasonable treatment was such an accomplishment that this disease became known as Stein-Leventhal Syndrome. However, with the advent of modern medical solutions, particularly the medication clomiphene citrate, removing a wedge of the ovary is rarely done today.
Through the 1960s and 1970s, improved lab testing allowed easier detection of the typical hormonal abnormalities of PCOS. Researchers discovered that an excess of male sex hormones called androgens, of which testosterone is the best known, causes the masculine appearance in women. Features associated with an excess of androgens, such as acne, male-pattern baldness, and facial hair growth, are often obvious in women, but measuring these hormones is not as useful for the diagnosis of PCOS as you may think. Androgen levels in women with PCOS are only modestly elevated and vary throughout the day and throughout the menstrual cycle, so it is difficult to make a diagnosis of PCOS based on biochemical analysis alone.
Figure 1.2. The normal ovary compared with the polycystic ovary. From Polycystic Ovary Syndrome, 2nd ed., Gabor T. Kovacs and Robert Norman, © Cambridge University Press, 2007. Reproduced with permission of the Licensor through PLSclear.
By the 1980s, the increasing availability of real-time ultrasound revolutionized the diagnosis of PCOS, because it meant laparotomy was no longer necessary to confirm the enlargement of the ovaries. In 1981 the ultrasound definition of polycystic ovaries was standardized, which allowed researchers to easily compare different cases.7 Further refinements included the introduction of transvaginal ultrasound (an ultrasound in which the probe is inserted into the vagina), which detects ovarian cysts with more precision because the probe is closer to the ovaries. This technology soon made clear that many otherwise-normal women also had multiple cysts on their ovaries. In fact, almost a quarter of women of reproductive age had polycystic ovaries without any other symptoms. Thus, it is important to distinguish between the presence of polycystic ovaries alone and polycystic ovary syndrome.
The 1980s also saw a revolution in our understanding of the underlying cause of PCOS. The root cause of the disease was originally ascribed to excessive exposure of female fetuses to androgens, but this hypothesis was ultimately refuted. Instead, studies increasingly linked PCOS to hyperinsulinemia, literally “too much insulin in the blood,” a condition commonly seen in association with insulin resistance. Because the syndrome was still known by a multitude of different names—polycystic ovaries disorder, a syndrome of polycystic ovaries, functional ovary androgenism, hyperandrogenic chronic anovulation, polycystic ovarian syndrome, ovarian dysmetabolic syndrome, sclerotic polycystic ovary syndrome, and so forth—researchers did not always know if they were talking about the same disease. To move forward in properly identifying and diagnosing the disorder, the terms would need to be standardized.
Attendees of the 1990 National Institute of Child Health and Human Development (NICHD) conference on PCOS took the first step when they agreed by consensus on the following specific criteria:
1.Evidence of excess androgens (symptomatic or biochemical)
2.Persistent rare or absent ovulatory cycles
Because these symptoms are not specific to PCOS, other diseases would still need to be ruled out. However, these so-called National Institutes of Health (NIH) criteria were a giant leap forward because proper classification allowed international collaboration between universities and researchers. Interestingly, the NIH criteria do not require evidence of polycystic ovaries, which obviously presented a problem for a disease known as polycystic ovary syndrome.
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