Galileo's Middle Finger (42 page)

The Swedish group had found
:
See Svetlana Lajic et al., “Long-Term Somatic Follow-up of Prenatally Treated Children with Congenital Adrenal Hyperplasia,”
Journal of Clinical Endocrinology & Metabolism
83, no. 11 (1998): 3872–80.

between 1 in 10,000 and 1 in 15,000
:
Maguelone G. Forest, “Recent Advances in the Diagnosis and Management of Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency,”
Human Reproduction Update
10, no. 6 (Nov./Dec. 2004): 469–85.
The NIH gives the frequency as “about 1 in 10,000 to 1 in 18,000” at
MedLine Plus
; see www.nlm.nih.gov/medlineplus/ency/article/000411.htm (accessed July 30, 2014).

drew patients from around the world
:
Chapter 9 includes a review of what numbers New reported to NIH.

most common cause of congenital ambiguous genitalia
:
National Institutes of Health, “Intersex,”
MedLine Plus
, www.nlm.nih.gov/medlineplus/ency/article/001669.htm (accessed July 30, 2014). CAH actually comes in a number of different forms, and not all forms lead to masculinization in genetic females. The main type we’re interested in here is the form called 21-hydroxylase deficiency.

substantial natural variation
:
See Medline Plus, “Congenital Adrenal Hyperplasia,” at http://www.nlm.nih.gov/medlineplus/ency/article/000411.htm.

ultimately identify as male
:
Heino F. L. Meyer-Bahlburg, “What Causes Low Rates of Child-Bearing in Congenital Adrenal Hyperplasia?”
Journal of Clinical Endocrinology and Metabolism
84, no. 6 (June 1999): 1844–47; Heino F. L. Meyer-Bahlburg et al., “Gender Development in Women with Congenital Adrenal Hyperplasia as a Function of Disorder Severity,”
Archives of Sexual Behavior
35, no. 6 (Dec. 2006): 667–84; and Arianne B. Dessens, Froukje M. E. Slijper, and Stenvert L. S. Drop, “Gender Dysphoria and Gender Change in Chromosomal Females with Congenital Adrenal Hyperplasia,”
Archives of Sexual Behavior
34, no. 4 (Aug. 2005): 389–97.

opted to abort
:
Selective abortion of females with CAH is reported, for example, in Arlene B. Mercado et al., “Extensive Personal Experience: Prenatal Treatment and Diagnosis of Congenital Adrenal Hyperplasia Owing to Steroid 21-Hydroxylase Deficiency,”
Journal of Clinical Endocrinology and Metabolism
80, no. 7 (July 1995): 2014–20.

A 1984 paper
:
Michel David and Maguelone G. Forest, “Prenatal Treatment of Congenital Adrenal Hyperplasia Resulting from 21-Hydroxylase Deficiency,”
Journal of Pediatrics
105, no. 5 (Nov. 1984): 799–803.

making the intervention available
:
See Chapter 9 for a review of the history of New’s use of prenatal dexamethasone.

Dr. New tells the families
:
Maria I. New, lecture presented at conference for CARES Foundation, Weill Medical College of Cornell University, New York, Nov. 14, 2001.

“done well in very few centers”
:
Ibid.

giving birth prematurely
:
Concerned researchers have been tracking possible unintended consequences of the use of prenatal steroids for premature birth risk; see, for example, National Institutes of Health Consensus Development Panel, “Antenatal Corticosteroids Revisited: Repeat Courses,” Statement of NIH Consensus Development Conference, Aug. 17–18, 2000,
Obstetrics and Gynecology
98, no. 1 (2001): 144–50; see also Noel P. French et al. “Repeated Antenatal Corticosteroids: Effects on Cerebral Palsy and Childhood Behavior,”
American Journal of Obstetrics and Gynecology
190, no. 3 (Mar. 2004): 588–95.

families steadily learned
:
For an example of a woman knowing to call Maria New, “a total stranger,” as soon as she was pregnant with a fetus who might have CAH, see Catherine Elton, “A Prenatal Treatment Raises Questions of Medical Ethics,”
Time,
June 18, 2010, http://content.time.com/time/health/article/0,8599,1996453,00.html.

pregnancy category C
:
FDA Pregnancy Categories, http://depts.washington.edu/druginfo/Formulary/Pregnancy.pdf (accessed July 30, 2014).

“despite potential risks”
:
Ibid.

the DES disaster
:
For a history of DES, see Nancy Langston,
Toxic Bodies: Hormone Disruptors and the Legacy of DES
(New Haven, CT: Yale University Press, 2010).

study published in 1953
:
William J. Dieckmann et al., “Does the Administration of Diethylstilbestrol During Pregnancy Have Therapeutic Value?,”
American Journal of Obstetrics and Gynecology
66, no. 5 (Nov. 1953): 1062–82.

serious question in 1971
:
See Langston,
Toxic Bodies;
see also Centers for Disease Control, “About DES,” www.cdc.gov/DES/CONSUMERS/about (accessed July 30, 2014).

fatal vaginal cancer
:
The first report of this cancer cluster’s tie to DES was Arthur L. Herbst, Howard Ulfelder, and David C. Poskanzer, “Adenocarcinoma of the Vagina: Association of Maternal Stilbestrol Therapy with Tumor Appearance in Young Women,”
New England Journal of Medicine
284, no. 15 (Apr. 15, 1971): 878–81.

Penny Stone
:
See DES Action, “Meet the Woman Who Was the First to Connect DES and Cancer,”
DES Action Voice
, no. 134 (Fall 2012): 8.

reproductive cancers
:
For a good overview of the harms caused by prenatal DES, see National Cancer Institute, “Diethylstilbestrol (DES) and Cancer,” www.cancer.gov/cancertopics/factsheet/Risk/DES (accessed July 30, 2014).

Frances Oldham Kelsey
:
See Gardiner Harris, “The Public’s Quiet Savior from Harmful Medicines,”
The New York Times
, Sept. 13, 2010, http://www.nytimes.com/2010/09/14/health/14kelsey.html.

ten thousand children in Europe
:
Centers for Disease Control and Prevention, “Thalidomide,” http://www.cdc.gov/healthcommunication/toolstemplates/entertainmented/tips/thalidomide.html.

David Sandberg
:
David Sandberg reviewed this account of our discussions and confirmed its accuracy, personal communication, Oct. 13, 2012.

sixty to a hundred times
:
Walter L. Miller, “Prenatal Treatment of Classic CAH with Dexamethasone: Con,”
Endocrine News
(Apr. 2008): 16–18.

All we had were reports
:
The problems with this approach are alluded to in Fernández-Balsells et al., “Prenatal Dexamethasone.”

data coming out of Sweden
:
See Hirvikoski et al., “Cognitive Functions.”

missing or choosing not to participate
:
In 2010, New’s chief collaborator, Heino Meyer-Bahlburg, admitted that “fewer than 50% of mothers and offspring have responded to questionnaires”: in Phyllis W. Speiser et al., “A Summary of the Endocrine Society Clinical Practice Guidelines on Congenital Adrenal Hyperplasia due to Steroid 21-Hydroxylase Deficiency,”
International Journal of Pediatric Endocrinology,
May 2010, www.ijpeonline.com/content/2010/1/494173; for quotation, see “3. Prenatal Treatment of CAH.”

“fetal programming”
:
The risk of fetal programming from prenatal dexamethasone was raised as early as 1997; see Jonathan R. Seckl and Walter L. Miller, “How Safe Is Long-Term Prenatal Glucocorticoid Treatment?,”
Journal of the American Medical Association
277, no. 13 (Apr. 2, 1997): 1077–79. For others raising the concern, see Hirvikoski et al., “Cognitive Functions.” For more recent analyses of prenatal glucocorticoids and the programming of adult disease, see Anjanette Harris and Jonathan Seckl, “Glucocorticoids, Prenatal Stress, and the Programming of Disease,”
Hormones and Behavior
59, no. 3 (Mar. 2011): 279–89.

Wall Street Journal
:
Bernard Wysocki Jr., “As Universities Get Billions in Grants, Some See Abuses: Cornell Doctor Blows Whistle over Use of Federal Funds, Alleging Phantom Studies,”
Wall Street Journal
(Aug. 16, 2005): A1.

Sarafoglou went to the Feds
:
Ibid.

only about 80 percent of the time
:
The authors of the formal pediatric endocrine consensus that emerged in 2010 (discussed in the next chapter) noted the poor quality of efficacy data and concluded only that “the groups advocating and performing prenatal treatment appear to agree that it is effective in reducing and often eliminating virilization of female fetal genitalia and that the success rate is about 80–85%”; see Phyllis W. Speiser et al., “Congenital Adrenal Hyperplasia due to Steroid 21-Hydroxylase Deficiency: An Endocrine Society Clinical Practice Guideline,”
Journal of Clinical Endocrinology and Metabolism
95, no. 9 (Sept. 2010): 4133–60.

had been warning
:
Seckl and Miller, “How Safe.”

Miller had finally declared
:
Miller, “Prenatal Treatment,” 17.

numerous medical societies
:
See, for example, Joint LWPES/ESPE CAH Working Group, “Consensus Statement on 21-Hydroxylase Deficiency from the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pædiatric Endocrinology,”
Journal of Clinical Endocrinology and Metabolism
87, no. 9 (Sept. 2002): 4048–53.

American Academy of Pediatrics
:
Jaime Frias, Lenore S. Levine, Sharon E. Oberfield, et al., “In Reply,” (letter to the editor)
Pediatrics
, vol. 107, no. 4 (2001): 805. The letter referred to “the memory of the tragedies associated with prenatal use of dexamethasone and thalidomide,” a line the authors later corrected to read “use of DES (diethylstilbestrol) and thalidomide”; see erratum,
Pediatrics
107, no. 6 (June 2001): 1450, http://pediatrics.aappublications.org/content/107/6/1450.full.

I wrote to her
:
Alice Dreger to Maria New, e-mail communication, Dec. 8, 2009.

Miami
:
Maria I. New, “Long Range Outcome of Prenatal Treatment,” conference presentation at 2nd World Conference, Hormonal and Genetic Basis of Sexual Differentiation Disorders and Hot Topics in Endocrinology, Jan. 15, 2010, Miami Beach.

was very poor
:
This was confirmed in Meyer-Bahlburg’s report in Speiser et al., “A Summary of the Endocrine Society Clinical Practice Guidelines.”

at least one boy exposed
:
The Swedish team formally published the evidence suggesting that boys exposed prenatally might be hypomasculinized in 2011 and 2012. See Lajic, Nordenström, and Hirvikoski, “Long-Term Outcome”; see also Tatya Hirvikoski et al., “Prenatal Dexamethasone Treatment of Children at Risk for Congenital Adrenal Hyperplasia: The Swedish Experience and Standpoint,”
Journal of Clinical Endocrinology and Metabolism
97, no. 6 (June 2012): 1881–83, doi:10.1210/jc.2012-1222.

plugging prenatal dex
:
See, for example, Maria I. New and Nathalie Josso, “Disorders of Sexual Differentiation,” in Lee Goldman and J. Claude Bennett, eds.,
Cecil Textbook of Medicine
, 21st ed. (Philadelphia: W. B. Saunders, 2000): 1297–1306; Maria I. New, Lucia Ghizzoni, and Karen Lin-Su, “An Update of Congenital Adrenal Hyperplasia,” in Fima Lifshitz, ed.,
Pediatric Endocrinology
, 5th ed. (New York: Informa Healthcare, 2007): 227–45.

Marsha Rappley
:
Conversation with Marsha Rappley; account confirmed by e-mail, Oct. 26, 2012.

another e-mail message
:
Alice Dreger to Maria New, e-mail communication, Jan. 24, 2010.

from Jeffrey Silverstein
:
Jeffrey H. Silverstein to Alice Dreger, e-mail communication, Jan. 26, 2010.

I asked Dr. Silverstein to clarify
:
Alice Dreger to Jeffrey H. Silverstein, e-mail communication, Jan. 26, 2010.

CHAPTER 8: DOCTOR, MY EYES

American medical ethics regulations
:
See the
Code of Federal Regulations
, Title 45, Part 46; for a sociological and historical analysis of institutional review boards (local ethics committees) in the United States, see Laura Stark,
Behind Closed Doors: IRBs and the Making of Ethical Research
(Chicago: University of Chicago Press, 2011).

New consistently described
:
For examples, see “Prenatal Diagnosis and Treatment of Congenital Adrenal Hyperplasia,” Maria New Children’s Hormone Foundation, www.newchf.org/testing.php (accessed July 30, 2014). See also Elizabeth Kitzinger, “Prenatal Diagnosis & Treatment for Classical CAH,”
CARES Foundation Newsletter
2, no. 1 (Winter 2003): 15, www.caresfoundation.org/productcart/pc/news_letter/winter02-03_page_9.htm. See also Maria I. New, lecture presented at conference for CARES Foundation, Weill Medical College of Cornell University, New York, Nov. 14, 2001.