Hydroxyprogesterone is a synthetic form of the hormone progesterone, most commonly used in medicine to help prevent preterm birth in pregnant women with a history of delivering early. It also plays a role in treating certain hormonal conditions and cancers. The term usually refers to 17-alpha-hydroxyprogesterone caproate, sold under the brand name Makena, though it can also refer to the naturally occurring hormone 17-hydroxyprogesterone that your body produces on its own.
The Natural Hormone vs. the Synthetic Drug
Your body naturally produces 17-hydroxyprogesterone (often abbreviated 17-OHP) in the adrenal glands and reproductive organs. It serves as a building block that your body converts into cortisol, a stress hormone, and into other sex hormones like testosterone and estrogen. In this natural form, 17-OHP isn’t a medication. It’s a routine part of hormone production that doctors measure through blood tests when screening for conditions like congenital adrenal hyperplasia, a genetic disorder where the body can’t properly convert 17-OHP into cortisol.
The synthetic version, 17-alpha-hydroxyprogesterone caproate (17-OHPC), is an injectable drug designed to mimic progesterone’s effects on the uterus. It was developed to last longer in the body than natural progesterone, allowing for weekly injections rather than daily dosing. This distinction matters because when most people encounter the term “hydroxyprogesterone” from a doctor or pharmacist, they’re almost always talking about the synthetic injectable.
How It Was Used in Pregnancy
For years, 17-OHPC was the standard treatment offered to women who had previously delivered a baby before 37 weeks of pregnancy. The logic was straightforward: progesterone helps maintain pregnancy by keeping the uterine lining stable and suppressing contractions. A synthetic version, given as a weekly intramuscular injection starting between 16 and 20 weeks of pregnancy and continuing through week 36, was thought to reduce the risk of another preterm delivery.
The drug’s trajectory in the U.S. tells an unusual story. An initial trial published in 2003 by the National Institute of Child Health and Human Development showed a significant reduction in recurrent preterm birth, dropping the rate from about 55% in the placebo group to roughly 36% in women who received the injections. Based on that trial, the FDA granted accelerated approval to the branded product Makena in 2011, with the requirement that the manufacturer conduct a larger confirmatory study.
That confirmatory trial, known as the PROLONG study, enrolled over 1,700 women across multiple countries and found no meaningful difference in preterm birth rates or newborn health outcomes between women who received 17-OHPC and those who received a placebo. The preterm birth rate was low in both groups, around 11%, suggesting the drug offered no added benefit. After reviewing this evidence, the FDA withdrew approval of Makena in 2023, a rare move that effectively ended the drug’s use for preterm birth prevention in the United States.
Why the Two Studies Disagreed
The contradiction between the original trial and the PROLONG study sparked significant debate. Several factors likely explain the difference. The original 2003 trial enrolled a higher-risk population, predominantly Black women in the United States with very high baseline rates of preterm birth. The PROLONG study enrolled women from a broader range of countries and backgrounds, and their overall risk of preterm birth turned out to be much lower than expected. When the baseline risk is already low, it becomes harder for any treatment to show a measurable benefit.
Some researchers have also pointed to differences in the care women received outside the study drug. Prenatal care practices improved between 2003 and the PROLONG study years, and women in both groups of the later trial may have benefited from better monitoring and interventions that weren’t as widely available during the earlier study. The result was that the placebo group in PROLONG did far better than anyone anticipated, narrowing any potential gap the drug might have filled.
Other Medical Uses
Beyond pregnancy, hydroxyprogesterone has been used in several other clinical contexts. In some countries, it is prescribed to treat irregular or absent menstrual periods caused by hormonal imbalances. It works by supplementing progesterone activity, which can trigger the shedding of the uterine lining and restore a more predictable cycle.
Hydroxyprogesterone caproate has also been used as part of treatment regimens for endometrial cancer and, less commonly, for advanced breast cancer. In these settings, the drug’s progesterone-like activity can slow the growth of hormone-sensitive tumors. These oncology uses are far less common today than they once were, as newer and more targeted therapies have largely replaced older hormonal approaches.
Side Effects and Risks
When 17-OHPC was widely used during pregnancy, the most common side effects were injection site reactions: pain, swelling, and itching where the shot was given. Because the drug is delivered as an oily intramuscular injection, soreness at the injection site was reported by a substantial portion of users.
Other reported side effects included nausea, bloating, headaches, and mood changes, effects consistent with progesterone-related medications in general. More serious but rare risks included allergic reactions, blood clots, and depression. Elevated blood sugar was also flagged as a concern for women with gestational diabetes or those at risk for it, since progesterone-type hormones can affect how the body processes glucose.
17-OHP as a Lab Test
If you encountered the term hydroxyprogesterone in the context of bloodwork rather than a prescription, it likely refers to a 17-OHP level test. This blood test measures how much of the natural hormone is circulating in your body and is primarily used to diagnose congenital adrenal hyperplasia (CAH). In the classic form of CAH, a missing enzyme prevents the body from converting 17-OHP into cortisol, causing 17-OHP levels to build up dramatically.
Newborn screening programs in many countries routinely check 17-OHP levels within the first few days of life because untreated CAH can cause life-threatening salt-wasting crises in infants. In adults and older children, the test is used to evaluate late-onset CAH, which can cause symptoms like excess body hair, acne, irregular periods, and fertility problems. Normal 17-OHP levels vary by age, sex, and the time of day the blood is drawn, but levels above 200 ng/dL in adults typically prompt further testing.
Current Status
With the FDA’s withdrawal of Makena, 17-OHPC is no longer an FDA-approved treatment for preterm birth prevention in the United States. Some compounding pharmacies still prepare the drug, and some clinicians continue to prescribe it off-label, though professional guidelines have shifted. The American College of Obstetricians and Gynecologists updated its guidance to reflect the PROLONG data, and vaginal progesterone (a different formulation applied locally rather than injected) has gained more attention as an alternative for certain women at risk of preterm delivery, particularly those with a short cervix detected on ultrasound.
For women who previously received 17-OHPC injections during a pregnancy, there is no evidence of long-term harm to children exposed in utero. Follow-up studies of children born to mothers in the original 2003 trial showed no differences in developmental outcomes through early childhood compared to children whose mothers received placebo.