Link Between Undescended Testes and OTC Pain Meds

Is it safe for pregnant women to take pain medications?

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Recently, there's been a lot of talk about the ingestion of over-the-counter (OTC) pain medications during pregnancy. These pain medications include Tylenol (Tylenol) and NSAIDs like Motrin (ibuprofen) and aspirin (acetylsalicylic acid). Specifically, when taken during pregnancy, OTC pain medications have been linked to various adverse effects and outcomes experienced by the baby, including ADHD, congenital heart defects (premature closure of the patent ductus arteriosus), and miscarriage.

One worrisome potential adverse effect of OTC pain medications is cryptorchidism, or failure of an infant's testicles to descend into the scrotum.

Although we don't exactly understand how aspirin and NSAIDs can potentially result in undescended testes, based on studies done in animals, researchers think it has something to do with hormone disruption during key gestational time periods. Please keep in mind that animals are different from people, and not all drug effects seen in animals necessarily translate into effects on humans. Nevertheless, animal studies can give us ideas about affects on humans and are often a first step in learning more about a drug's effects on man.

Tylenol and NSAIDs are cyclooxygenase inhibitors and thus interfere with prostaglandin synthesis. Prostaglandins likely play a role in androgen and testosterone synthesis. During pregnancy, stimulation by such androgens is necessary for the testes to properly descend into the scrotum.

Usually by the age of nine months, the testicles of an infant boy descend into the scrotum. Undescended testicles can lead to sterility and testicular cancer. When a baby's testicles don't descend, he may be treated with hormones or surgery.

In 2010, Danish researchers published results from a study examining the link between aspirin, acetaminophen and ibuprofen use in expectant mothers and cryptorchidism in their male infants. These researchers pulled results from a database of 47,400 male births between 1996 and 2002 thus identifying cases of 980 cases of childhood cryptorchidism. To assess ingestion of pain medications during pregnancy, researchers used a mix of prospective and retrospective questionnaires and interviews to solicit information from the participating mothers.

The researchers adjusted for possible confounding variables including maternal age, cigarette use, and infertility. Furthermore, researchers also accounted for cryptorchidism that occurred in children after the study ended. Because cryptorchidism could present later in childhood, researchers used regression analysis to estimate later presentation of undescended testes.

The researchers found a small but significant increase in the risk of cryptorchidism in mothers taking Tylenol—but not NSAIDs—during the first and second trimester. This risk was more pronounced in women who took acetaminophen for more than four weeks.

In January 2015, the FDA examined existing studies and weighed in on the potential risk of pain medications to expectant mothers and their unborn children. The FDA found that these studies "have potential limitations in their designs; sometimes the accumulated studies on a topic contained conflicting results that prevented us from drawing reliable conclusions." In other words, the FDA determined that there just isn't enough good evidence out there—ostensibly including the Danish study on cryptorchidism—to definitively state that OTC and prescription pain medications are dangerous to mothers and babies.

If you or a loved one are in pain and need to take either OTC or prescription pain medication during pregnancy, please consult with your physician first—especially if you take these medications regularly. Persistent pain during pregnancy can lead to anxiety, depression, and high blood pressure and requires medical attention. However, the analgesic properties of pain medications must be carefully weighed against any potential risk.

On a final note, please remember that taking OTC pain medications every day is a likely indicator of a more serious problem. Pain can be a symptom of something more serious—an issue that requires medical attention. Whether pregnant or not, if you are regularly taking pain medications, please inform your physician. Your primary care physician will be able to determine whether you need specific treatment and refer you to a specialist as needed. Even though many drugs are sold without prescription, this doesn't mean that they're safe. All drugs have adverse effects. 

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  • Jensen MS, et al. Maternal Use of Acetaminophen, Ibuprofen, and Acetylsalicylic Acid During Pregnancy and Risk of Cryptorchidism. Epidemiology. 2010; 21:779-85.
  • Risser A, et al. NSAID Prescribing Precautions. American Family Physician. December 15, 2009.