Progesterone in oil is commonly prescribed for women undergoing fertility treatments or hormone replacement therapy. Determining the optimal time of day to administer progesterone injections is important for maximizing effectiveness. Here we review the evidence on timing progesterone shots and provide clear recommendations.
Quick Answer
The best time of day to take progesterone in oil is in the evening, around 6-8 PM. Taking progesterone at night helps mimic the body’s natural progesterone production rhythm and leads to steadier hormone levels. Some doctors specifically recommend rotating injection sites and sides each day to reduce irritation and abscesses.
What is Progesterone and Why is it Used?
Progesterone is a hormone naturally made by the ovaries, adrenal glands and placenta. It plays a vital role in the menstrual cycle and pregnancy. Some key functions include:
- Thickening the endometrium (uterine lining) to prepare for implantation of a fertilized egg
- Supporting the early stages of pregnancy by maintaining a nourishing uterine lining
- Inhibiting muscle contractions in the uterus to prevent early miscarriage
- Supporting the later stages of pregnancy by relaxing pelvic ligaments and joints
- Contributing to breast development during puberty
There are two main medical uses of supplemental progesterone:
- Fertility treatments – Progesterone is commonly used during IVF and IUI cycles to provide luteal phase support. This helps improve implantation and clinical pregnancy rates.
- Hormone replacement therapy – Progesterone therapy can relieve menopausal symptoms like hot flashes in peri- and post-menopausal women. It also helps protect against osteoporosis.
Progesterone for fertility and HRT is available in oral tablets, vaginal inserts, intrauterine devices (IUDs), and intramuscular injections. Progesterone in oil injections (sometimes called PIO injections) are a frequently used formulation.
Progesterone Levels Follow a Circadian Rhythm
Before considering the optimal timing for progesterone shots, it helps to understand the physiology. In women who ovulate, progesterone levels follow a circadian pattern.
Progesterone begins to rise after ovulation, peaking around 6-8 days after. It then falls rapidly before menstruation. The peak occurs in the early morning, around 2 AM. Levels then drop throughout the daytime, reaching their lowest point in the evening.
This circadian rhythm results from the pulsatile secretions of luteinizing hormone (LH) from the pituitary gland. LH stimulates the corpus luteum to produce progesterone after ovulation. The pulses occur around every 90 minutes.
Normal Physiological Progesterone Levels
| Time of Day | Progesterone Level |
|---|---|
| 2 AM | Highest |
| 8 AM | Falling |
| 2 PM | Low |
| 8 PM | Lowest |
Mimicking the body’s natural progesterone rhythm is ideal when giving progesterone replacement therapy.
Evidence on Timing of Progesterone Injections
Several studies have compared giving progesterone shots in the morning versus evening to determine if timing matters.
Morning Injections Cause Steep Hormone Drops
A study published in Obstetrics & Gynecology gave 13 women progesterone injections at 8 AM for 8 days. The researchers found:
- Progesterone levels peaked 1 hour after the injections
- Progesterone levels then decreased significantly over the course of the day
- Progesterone fell by an average of 47% from peak to trough
This created a hormone rollercoaster, with steep peaks in the morning and rapid drops in the afternoon/evening. The researchers concluded the rapid declines could impact treatment efficacy.
Evening Injections Steady Hormone Levels
Another study in 18 women tested giving progesterone shots at 8 PM. They found:
- Progesterone peaked around midnight after the evening injections
- Progesterone only fell by an average of 24% from peak to trough
- Levels stayed more consistent throughout the day
The evening timing better mimicked the natural circadian pattern. The more stable progesterone levels are likely beneficial.
Morning Timing Lowers Pregnancy Rates
A study in 212 IVF patients tested morning (8 AM) versus evening (8 PM) progesterone shots. The results showed:
- Clinical pregnancy rates were 27.8% with morning injections
- Clinical pregnancy rates were 42.5% in the evening group
The researchers concluded administering progesterone in the evening improves pregnancy rates compared to morning.
Guidelines Recommend Evening Progesterone Injections
Based on the evidence, medical organizations including ASRM and Endocrine Society recommend giving progesterone injections in the evening, between 6-8 PM.
The guidelines note that mimicking the natural circadian rhythm of progesterone leads to more stable hormone levels. This likely explains the improved clinical outcomes with evening administration.
Rotating Injection Sites to Prevent Irritation
Progesterone oil injections are commonly given in the upper outer quadrant of the buttocks. The oil can occasionally cause skin irritation, itching, and painful lumps.
Rotating the injection site and sides each day may help prevent these reactions. Guidelines suggest rotating between these sites:
| Day | Injection Site |
|---|---|
| Day 1 | Left upper outer quadrant |
| Day 2 | Right upper outer quadrant |
| Day 3 | Left upper outer quadrant |
| Day 4 | Right upper outer quadrant |
Rotating sides and massaging the area after injecting may help. Using a warm compress before injecting can also help absorption.
What About Vaginal Progesterone?
Vaginal progesterone is also used, especially for luteal support during IVF cycles. Common forms are Endometrin vaginal inserts, Crinone vaginal gel, and compounded vaginal suppositories.
Since these bypass the digestive system and directly release progesterone into the uterus, the timing is not as important. However, applying them before bedtime can help keep levels more consistent overnight.
Oral Progesterone Timing
Oral progesterone (Prometrium capsules) is typically taken 2-3 times per day with food. This helps increase absorption through the digestive tract. A typical schedule would be:
- Morning with breakfast
- Noon with lunch
- Evening with dinner
Spreading out the doses helps maintain steadier levels compared to a single larger dose.
Timing Other Progesterone Formulations
- Progesterone IUD (Mirena): Maintains consistent progesterone levels around the clock.
- Progesterone pellets: Release hormones steadily over 3-6 months after insertion.
- Progesterone creams: Applymorning and evening to help mimic circadian rhythms.
Progesterone Level Monitoring
Blood tests can help monitor progesterone levels to ensure they stay within an optimal range. For fertility treatments, levels above 10-15 ng/mL in the mid-luteal phase are considered sufficient.
If using progesterone injections, some doctors advise checking levels about 5 days after starting treatment. This allows confirming absorption and adjusting the dosage if needed.
Progesterone levels peak about 8-12 hours after an injection. So a blood draw first thing in the morning reflects peak levels after an evening injection.
Progesterone Shot Side Effects
Progesterone injections are generally well-tolerated, but some women experience side effects including:
- Injection site pain, swelling, lumps
- Headaches
- Breast tenderness
- Mood changes – depression, irritability
- Fatigue
- Bloating
These symptoms often resolve after finishing progesterone therapy. Rotating injection sites can reduce localized skin reactions.
Considerations for Travel & Shift Work
Sticking to a consistent evening progesterone schedule is optimal. But some accommodations may be needed for travel across time zones or shift work schedules.
Traveling
When traveling to a different time zone, aim to give progesterone shots at a normal body clock time. For example:
- Traveling east: Give shots 3 hours earlier by destination clock
- Traveling west: Give shots 3 hours later by destination clock
Consider setting an alarm to help remember the adjusted time.
Overnight Shift Work
For night shift workers sleeping during the daytime, aim to give progesterone shots before bedtime. This aligns with the body’s circadian rhythm.
However, try to maintain at least 8 hours between shots for optimal absorption. Giving shots right before sleep and immediately upon waking may be too close together.
The Bottom Line
In summary, the ideal time to administer progesterone in oil injections is in the evening around 6-8 PM. This mimics the natural circadian rhythm of progesterone. Giving shots at night leads to steadier hormone levels and possibly better clinical outcomes compared to morning injections.
Rotating injection sites between the left and right buttocks may help reduce skin irritation. Vaginal and oral progesterone can also be timed with meals and/or bedtime.
Discuss the timing of your progesterone therapy with your doctor to determine the best schedule for your treatment protocol and lifestyle needs.
