Understanding Progesterone Injections
Progesterone is a crucial hormone for regulating the menstrual cycle and maintaining a healthy pregnancy [1.7.2]. While the body produces it naturally, supplemental progesterone is often required in specific medical situations. Progesterone injections are administered intramuscularly, typically in the buttocks or thigh, and are used for several reasons, including supporting pregnancies from in-vitro fertilization (IVF) and preventing preterm birth in at-risk women [1.6.4, 1.8.3].
There are two common types of injectable progesterone:
- Progesterone in Oil (PIO): This form is frequently used in fertility treatments. The progesterone is suspended in an oil (like sesame or ethyl oleate) which allows for its slow release into the bloodstream. It's typically administered daily [1.7.4].
- Hydroxyprogesterone Caproate (17-OHPC): Often known by the brand name Makena, this long-acting synthetic version is used to reduce the risk of recurrent preterm birth in women with a history of it. It is usually given as a weekly injection [1.8.2, 1.8.3].
How Your Body Processes Progesterone
After an intramuscular injection, the progesterone is slowly absorbed from the oil depot in the muscle into the bloodstream. For progesterone in oil, levels peak in the body after about 8 hours and remain elevated for roughly 24 hours [1.7.4]. The hormone is then primarily metabolized by the liver and its byproducts are excreted through urine and feces [1.4.1, 1.5.2]. It is important to note that with 17-OHPC, the hormone is not a prodrug of progesterone, meaning it is not converted into progesterone in the body; it acts on the progesterone receptors directly [1.4.1].
So, How Long Does a Progesterone Shot Stay in Your System?
The duration a progesterone shot remains detectable and active in your system is determined by its elimination half-life—the time it takes for the concentration of the drug in the body to be reduced by half. It takes about five to six half-lives for a drug to be almost completely cleared from the system [1.4.2].
- Progesterone in Oil (Intramuscular): This form has an elimination half-life of about 20–28 hours [1.3.2]. Because it is administered daily during fertility treatments, stable levels are maintained. Once the injections are stopped, it can take several days (approximately 5-7 days) for the hormone to clear from the system.
- Hydroxyprogesterone Caproate (17-OHPC): This long-acting version has a much longer half-life. In non-pregnant women, the half-life is about 7-8 days [1.4.1]. However, during pregnancy, this extends to about 16 or 17 days for a singleton pregnancy [1.4.1, 1.4.3]. Because of this long half-life, weekly injections are effective, but it also means the drug stays in the system for an extended period after the last dose, with some studies detecting it up to 44 days later [1.2.1, 1.4.1, 1.4.5].
Key Factors That Influence Duration
Several individual factors can affect how quickly your body metabolizes and eliminates progesterone:
- Type of Progesterone: As detailed above, the ester used (e.g., caproate) significantly lengthens the half-life compared to progesterone in oil [1.4.1].
- Dosage and Frequency: Higher doses and more frequent injections will lead to higher concentrations in the body, potentially taking longer to clear.
- Individual Metabolism: Liver function plays a primary role in breaking down progesterone. Variations in liver enzyme activity can speed up or slow down this process [1.5.2].
- Body Mass Index (BMI): Progesterone is lipophilic, meaning it can be stored in fat tissue. Individuals with a higher BMI may store more of the hormone, leading to a slower release and longer clearance time. Studies have shown an inverse relationship between BMI and plasma concentrations of 17-OHPC [1.4.2, 1.4.4].
- Gestation: Pregnancy itself alters drug metabolism. The half-life of 17-OHPC is significantly longer in pregnant women compared to non-pregnant women [1.4.1].
Comparison of Progesterone Injections
| Feature | Progesterone in Oil (PIO) | Hydroxyprogesterone Caproate (17-OHPC) |
|---|---|---|
| Common Use | IVF Luteal Phase Support [1.7.4] | Prevention of Recurrent Preterm Birth [1.8.2] |
| Injection Frequency | Daily [1.7.4] | Weekly [1.2.1] |
| Elimination Half-Life | ~20-28 hours [1.3.2] | ~16-17 days (in singleton pregnancy) [1.4.1] |
| Typical Clearance Time | A few days after cessation | Several weeks to over a month [1.4.1, 1.4.5] |
| Administration | Intramuscular injection [1.6.4] | Intramuscular injection [1.8.3] |
Potential Side Effects
Common side effects for both types of injections include reactions at the injection site, such as pain, swelling, itching, or bruising [1.2.1, 1.6.4]. Other possible side effects are breast tenderness, headache, weight changes, dizziness, and mood swings [1.6.2, 1.6.3]. More serious but rare side effects can include blood clots, so it's essential to discuss your full medical history with your doctor [1.6.1, 1.6.5].
Visit the Cleveland Clinic for more information on Progesterone Injections.
Conclusion
How long a progesterone shot stays in your system varies significantly, from a matter of days for daily progesterone in oil shots used in IVF to over a month for the weekly hydroxyprogesterone caproate injections used to prevent preterm labor. The specific formulation is the most critical determinant, but individual factors like metabolism, BMI, and pregnancy status also play a vital role. Understanding these differences is key for patients and healthcare providers to manage treatment expectations and potential side effects effectively.
