Progesterone injection may up risk of early-onset cancer in offspring

Using 17α-hydroxyprogesterone caproate (17-OHPC) to treat habitual and threatened abortion in pregnant women poses an increased future risk of cancer among their children, according to a study.

Specifically, adults exposed to the drug in utero are twice as likely as those who had no such exposure to develop any cancer, and this association was strong for colorectal and prostate malignancies, said lead study researcher Dr Caitlin Murphy, an assistant professor at the University of Texas Southwestern Medical Center in Dallas, Texas, US.

“The findings support susceptibility of multiple organ systems to endocrine disruption during early development and risk of cancer decades later, and may partly explain increasing rates of early-onset colorectal cancer,” Murphy added. She presented the data virtually at the Endocrine Society's annual meeting (ENDO 2021).

Murphy and her team used data from the Child Health and Development Studies and looked at 18,751 live births among a cohort of women who received prenatal care in 1959–1966. Only a few mothers (n=181, 1.0 percent) received 17-OHPC in early pregnancy (defined as days 1–140 of gestation) for threatened abortion (54.0 percent) mainly. Other indications were amnionitis (9.4 percent) and incompetent cervix (3.0 percent).

There were 954 cancer cases diagnosed in the adult children (ages 18–58 years). Breast cancer (20.9 percent) was the most common malignancy, followed by cervical (10.9 percent), colorectal (7.1 percent), and prostate (5.9 percent) cancer, and melanoma (9.2 percent). [ENDO 2021, abstract OR11-1]

Despite the small number of mothers who had used 17-OHPC in pregnancy, in utero exposure to the drug was more common in the group of adult children who developed cancer (n=18, 1.9 percent) than in the group who did not (n=163, 0.9 percent).

In utero exposure to 17-OHPC was associated with twofold greater odds of the future development of any cancer in the offspring (odds ratio [OR], 2.08, 95 percent confidence interval [CI], 1.27–3.40). There was a surprising dramatic risk increase for colorectal (OR, 4.78, 95 percent CI, 1.49–15.41) and prostate (OR, 3.83, 95 percent CI, 0.93–15.83) cancers.

Conditions indicating 17-OHPC exerted no influence on the risk of any cancer, and neither did the use of other progestogens within 6 months prior to pregnancy (medroxyprogesterone acetate: n=50 mothers; OR, 0.38, 95 percent CI, 0.05–2.76).

OHPC is a synthetic progestogen hormone introduced in the 1950s to treat habitual and threatened abortion in pregnant women. “There is compelling evidence that some synthetic hormones cause endocrine disruption during early foetal development that may lead to cancer later in life for the offspring,” Murphy said.

“For example, progestogens have been implicated in cancer, and trends in the use of 17-OHPC in early pregnancy during the 1950s and 60s [demonstrate] parallel increasing incidence rates of certain cancers in young adults, such as early-onset colorectal cancer, born during that time,” she said.

As such, even with incomplete understanding of mechanisms of carcinogenesis, Murphy cautioned against the use of 17-OHPC and other endocrine-active pharmaceuticals in early pregnancy. This is important, she said, “especially in the absence of a clear short-term benefit and given the possible effect on risk of cancer in adult offspring.”