Risks and Benefits of the Use of Hormonal Pregnancy Test Tablets

Gal, Isabel

doi:10.1038/240241a0

Cited by 32 publications

(8 citation statements)

References 5 publications

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“…Such tests had also been used in 22 of 323 control pregnancies that produced normal children, and the difference between these groups was not statistically significant. Following the report of Laurence et al (1971), Gal (1972) reexamined their previously reported data and concluded that even when such factors as maternal age and reproductive history were controlled for, there was still a significant association between NTDs and exposure to sex hormones during pregnancy. Laurence (1972) and Sever (1973) further criticized Gal's (1967Gal's ( , 1972 analysis, noting that most pregnancy tests in Gal's series were administered after the closure of the neural tube, and therefore were unlikely to have produced some of the reported nervous system malformations.…”

Section: -1976: Epidemiological Studies Of Sex Steroid Exposure Amentioning

confidence: 84%

Nongenital malformations following exposure to progestational drugs: The last chapter of an erroneous allegation

Brent

2005

Birth Defect Res A

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In the late 1960s and 1970s, a number of epidemiological studies were published indicating that pregnant women who were exposed to an array of sex steroids delivered infants with an increased incidence of nongenital congenital malformations. Because of these publications, the Food and Drug Administration (FDA), in conjunction with various pharmaceutical companies, labeled the therapeutic exposure of progestational drugs and contraceptives in pregnant women as a risk factor for limb-reduction defects (LRDs) and congenital heart defects (CHDs). Subsequently there was a rapid decrease in the exposure of pregnant women to these drugs and the initiation of numerous lawsuits alleging that a particular progestational drug was responsible for a child's nongenital congenital malformation. Wilson and Brent (1981) published an article indicating that epidemiological and animal studies of these drugs, and basic science did not support the package insert's warnings. Many new and previous animal and epidemiological studies did not support the FDA box warning. In 1987 the FDA held a hearing in which the FDA, the Teratology Society, the Centers for Disease Control and Prevention, the American College of Obstetrics and Gynecology, and other organizations supported the position that progestational agents did not result in nongenital malformations. An editorial appeared in Teratology congratulating the FDA for removing the warning label on oral contraceptives regarding nongenital malformations. In 1999 the FDA published new wording for package inserts that removed warnings for nongenital malformations for all progestational agents. In spite of the recent changes in the package inserts, lawsuits have alleged that progestational drugs cause nongenital malformations. It took 22 years from the time a box warning was required by the FDA until the warnings were removed in 1999. The 1999 FDA publication, which is a scholarly and objective document, should put an end to 2 decades of concern and anxiety for pregnant women or women of reproductive age. Could scientists, the pharmaceutical companies, or the FDA have prevented the mislabeling of progestational drugs with regard to their teratogenic risks? Was the epidemiological or teratology community at fault because they did not critique and respond to the early publications? Did the FDA act too slowly? The epidemiologic analyses, animal studies, and basic science principles have been reviewed, and it is obvious that clinically utilized progestational drugs do not cause nongenital malformations (i.e., LRDs and CHDs).

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Section: -1976: Epidemiological Studies Of Sex Steroid Exposure Amentioning

confidence: 84%

Nongenital malformations following exposure to progestational drugs: The last chapter of an erroneous allegation

Brent

2005

Birth Defect Res A

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“…For example, Isabel Gal first reported concerns of malformations in the children of mothers exposed to HPTs in 1967 14 , pointing out that bleeding often occurred in pregnant women soon after exposure and suggesting that that would affect the "equilibrium" of the uterus. Between 5 and 11% of exposed women had bleeding, and the RCGP survey reported induced abortions in about 10% of women 15 .…”

Section: Discussionmentioning

confidence: 99%

“…For the association between exposure to oral HPTs and nervous system malformations in the offspring, five studies provided data: three case-control studies (Gal 1972;Laurence 1971;Sainz 1987) and two cohort studies (Roussel 1968;Torfs 1981), including 12 486 mothers of infants and 127 exposed (Figure 4). The pooled OR = 2.98 (95% CI 1.32 to 6.76; P = 0.009; I 2 = 78%).…”

Section: Quality Assessment Of Included Studiesmentioning

confidence: 99%

Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis

et al. 2018

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Background: Oral hormone pregnancy tests (HPTs), such as Primodos, containing ethinylestradiol and high doses of norethisterone, were given to over a million women from 1958 to 1978, when Primodos was withdrawn from the market because of concerns about possible teratogenicity. We aimed to study the association between maternal exposure to oral HPTs and congenital malformations. Methods: We have performed a systematic review and meta-analysis of case-control and cohort studies that included data from pregnant women and were exposed to oral HPTs within the estimated first three months of pregnancy, if compared with a relevant control group. We used random-effects meta-analysis and assessed the quality of each study using the Newcastle–Ottawa Scale for non-randomized studies. Results: We found 16 case control studies and 10 prospective cohort studies, together including 71 330 women, of whom 4209 were exposed to HPTs. Exposure to oral HPTs was associated with a 40% increased risk of all congenital malformations: pooled odds ratio (OR) = 1.40 (95% CI 1.18 to 1.66; P<0.0001; I2 = 0%). Exposure to HPTs was associated with an increased risk of congenital heart malformations: pooled OR = 1.89 (95% CI 1.32 to 2.72; P = 0.0006; I2=0%); nervous system malformations OR = 2.98 (95% CI 1.32 to 6.76; P = 0.0109 I2 = 78%); gastrointestinal malformations, OR = 4.50 (95% CI 0.63 to 32.20; P = 0.13; I2 = 54%); musculoskeletal malformations, OR = 2.24 (95% CI 1.23 to 4.08; P= 0.009; I2 = 0%); the VACTERL syndrome (Vertebral defects, Anal atresia, Cardiovascular anomalies, Tracheoesophageal fistula, Esophageal atresia, Renal anomalies, and Limb defects), OR = 7.47 (95% CI 2.92 to 19.07; P < 0.0001; I2 = 0%). Conclusions: This systematic review and meta-analysis shows that use of oral HPTs in pregnancy is associated with increased risks of congenital malformations.

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“…Most well known is the risk of carcinoma of the vagina among female offspring of women who have taken diethylstilbestrol (DES) during pregnancy (6). Gal and others (3,4) have also reported an association between increased incidence of congenital malformations of the central nervous system and the use of oral hormonal pregnancy tests containing ethinylestradiol and norethisterone acetate or ethisterone. The administration of sex hormones in the form of birth control pills during early pregnancy has also been implicated in an increased risk of heart and limb reduction defects (5,8).…”

Section: Discussionmentioning

confidence: 99%

Estrogen-Progesterone Withdrawal Bleeding in Diagnosis of Early Pregnancy

Vengadasalam

Lean

Kessel

et al. 1976

International Journal of Gynecology & Obstetrics

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This study was designed to evaluate the efficacy of an exogenous estrogen-progesterone preparation for inducing "withdrawal bleeding" in non-pregnant women, a procedure used in some areas for the diagnosis of early pregnancy. Three hundred patients not desiring to be pregnant and with no signs of pregnancy other than menses delayed by 14 days or less were randomly assigned to treatment or control groups. The treatment group received an intramuscular injection of 50 mg progesterone and 3 mg oestradiol benzoate in oil. The control group received no hormonal injection. There was no significant difference between the two groups in the incidence of uterine bleeding within 7 days. Thus, the hormonal preparation was ineffective in inducing "withdrawal bleeding". Its use as a diagnostic test for pregnancy is not recommended.

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Risks and Benefits of the Use of Hormonal Pregnancy Test Tablets

Cited by 32 publications

References 5 publications

Nongenital malformations following exposure to progestational drugs: The last chapter of an erroneous allegation

Nongenital malformations following exposure to progestational drugs: The last chapter of an erroneous allegation

Oral hormone pregnancy tests and the risks of congenital malformations: a systematic review and meta-analysis

Estrogen-Progesterone Withdrawal Bleeding in Diagnosis of Early Pregnancy

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