No reports describing the use of 17α-HP during human lactation have been located. Because of its use for the prevention of preterm birth, it is doubtful if such reports will ever be available. However, in 2001 the American Academy of Pediatrics classified progesterone as compatible with breastfeeding (35).

17α-HP is not available commercially in the United States but is prepared by some compounding pharmacies. It is a naturally occurring metabolite of progesterone (3).

Human Data: The Collaborative Perinatal Project monitored 866 mother-child pairs with 1st trimester exposure to progestational agents (including 162 with exposure to 17α-HP) (4, pp. 389, 391). An increase in the expected frequency of cardiovascular defects and hypospadias was observed for both estrogens and progestogens (4, p. 394; 5). Reevaluation of these data in terms of timing of exposure, vaginal bleeding in early pregnancy, and previous maternal obstetric history, however, failed to support an association between female sex hormones and cardiac malformations (6).

Dillon reported six infants with malformations exposed to 17α-HP during various stages of gestation (7,8). The congenital defects included spina bifida, anencephalus, hydrocephalus, tetralogy of Fallot, common truncus arteriosus, cataract, and ventricular septal defect. Complete absence of both thumbs and dislocated head of the right radius in a child have been associated with 17α-HP (8). However, the use of diazepam in early pregnancy and the lack of similar reports make an association doubtful.

In 2000, Schardein (9) reviewed the risk of progestogens for female masculinization and male feminization after 1st trimester use. He cited seven cases of female masculinization with 17α-HP. Although admitting that the relationship between progestogens and male feminization was still tenuous, among 78 cases there were 7 cases of hypospadias and/or ambiguous genitals associated with 17α-HP and 2 cases of hypospadias with progesterone (9).

A 1985 study described 2754 offspring born to mothers who had vaginal bleeding during the 1st trimester (10). Of the total group, 1608 of the newborns were delivered from mothers treated during the 1st trimester with oral medroxyprogesterone (20-30 mg/day), 17-hydroxyprogesterone (500 mg/week by injection), or a combination of the two. Medroxyprogesterone was used exclusively in 1274 (79.2%) of the study group. The control group consisted of 1146 infants delivered from mothers who bled during the 1st trimester but who were not treated. There were no differences between the study and control groups in the overall rate of malformations (120 vs. 123.9/1000, respectively) or in the rate of major malformations (63.4 vs. 71.5/1000, respectively) (10). Another 1985 study compared 988 infants exposed in utero to various progesterones with a matched cohort of 1976 unexposed controls (11). No association between the use of progestins, primarily progesterone and 17α-HP, and fetal malformations was discovered.

Developmental changes in the psychosexual performance of boys have been attributed to in utero exposure to 17α-HP (12). The mothers received an estrogen-progestogen regimen for their diabetes. Hormone-exposed males demonstrated a trend to have less heterosexual experience and fewer masculine interests than controls (12).

A number of studies have reported the use of 17α-HP during pregnancy or its benefits to prevent premature labor (13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31). The hormone is not effective in twin pregnancies (3,22). A 2005 meta-analysis of randomized controlled trials of progestational agents, most of which (80%) involved 17α-HP, concluded that these agents reduced the incidence of preterm birth and low-birth-weight newborns (32). In another 2005 review, the clinical use of 17α-HP for the prevention of preterm delivery and its safety was summarized (3). No increase in the incidence of fetal adverse effects has been observed. The evidence supports the use of 17α-HP (250 mg IM every week) beginning as soon as possible after 16 weeks and continuing to 36 weeks (3).

17α-HP also has been used in early gestation to prevent spontaneous abortion, but the results have been mixed (33,34).