Progesterone is a hormone produced principally by the ovary after ovulation. One of its major roles is to prepare the lining of the uterus (the endometrium) to allow the embryo to implant and grow.
In some of the treatment protocols progesterone is not produced by the ovary in adequate amounts, or its effect on the lining of the uterus is inadequate. This problem is called luteal deficiency. It is more common in older women and in women with abnormal ovulation.
There are different forms of progesterone to choose from.
• Daily oral progesterone
• Daily intamuscular injections e.g. gemstone
• Daily vaginal pessaries e.g. cyclogest. These are mounted in wax, which melts as progesterone is absorbed causing discharge. It may be necessary to wear a panty liner.
• Daily vaginal tablets e.g. Utrogestan
• Daily vaginal gel e.g. crinone 8%
Injectable progesterone (Progestrone given intramuscular [IM])
Injection of progesterone produces the highest blood levels.
Natural progesterone is dissolved in an oil for injection.
Because of the body’s rapid metabolism of progesterone, the injection should be given daily to maintain adequate blood progesterone levels.
Progesterone suppositories or creams
The absorption of progesterone through the vagina is more variable.
Blood levels are less predictable but progesterone may exert a direct local effect when absorbed through genital tissue.
The oral progesterone capsule is a relatively new way to take progesterone. This avoids the possible complications of pain and abscess formation associated with injections.
Oral progesterone is rapidly absorbed into the circulation.
For best blood levels, this should be taken twice a day.
On a theoretical basis, the metabolism of progesterone given orally could be different from the way progesterone is broken down when it is given either vaginally or intramuscularly.
The oral progesterone is well tolerated with side-effects in some women of dizziness or sleepiness. This can be minimized by taking the highest dose of progesterone at night. Care must nevertheless be exercised when taking oral progesterone, especially for the first three days, to avoid complications related to drowsiness.
Injectable progesterone – Progesterone given intra-muscular (IM)
Progesterone comes in a multi-dose vial. Because progesterone in suspended in an oil base, the mixture is thick, making the injection more difficult. However, the medication can be warm once it is drawn into the syringe, to make the injection easier
Please follow these steps:
1. Always wash your hands.
2. Take out the vial of medication; check the name and expiration date before removing the protective cap. Do not remove the rubber stopper.
3. Unwrap a 3cc, 22 gauge syringe with the 11/2″ needle; keeping the cap on the needle, unscrew it from syringe and place it aside as you will need to re-attach it for the injection. Replace the 22-gauge needle with the 18-gauge (pink) one.
4. Wipe the rubber stopper with alcohol.
5. Pull back halfway on the plunger to fill the syringe with air. Push the needle through the rubber stopper and push on the plunger to inject air into the vial.
6. Keeping the needle in the vial, turn it upside down and make sure that the needle tip is below the level of the medication.
7. Draw back on the plunger to fill the syringe halfway with progesterone; push the plunger up to the instructed dosage level of 1/2 cc or 1cc, expelling excess medication, air and bubbles back into the vial.
8. Remove the syringe from the bottle and draw the progesterone back into the syringe.
9. At this point, you may put the filled syringe in warm tap water to thin the medication and make administration easier.
10. Place the cap back on the 18-gauge needle, twist it off and replace it with the 22-gauge needle for the injection.
11. Push the plunger forward to expel air, being careful not to lose any medication.
Injecting the medication
• Cleanse the injection site with alcohol. Wait a few seconds until alcohol has dried on skin. Remove cap from needle.
• Insert needle quickly in a dart-like motion 90-degrees to the skin as far as it will go.
• Anchor syringe with your free hand. Pull back slightly on the plunger, if you see blood return, remove the needle and re-inject in an alternate site.
• If there is no blood return, inject medication slowly.
• Withdraw the needle at the same angle at which it was inserted. Apply pressure at the injection site with gauze or tissue.
• Dispose of used needle and syringes carefully in an approved sharps container.
• Alternate sides with each injection.
Note: If the uncovered needle touches any surface other that the inside of the medication vial prior to injection, it is contaminated. Twist off needle and replace with a sterile needle. Use all needles and syringes for 1 injection only.
Injection sites for intramuscular injections (IM)
The upper-outer quadrant of the buttock (right or left) is the recommended site for intramuscular injections. As an alternative only, injections may be given to the upper front quadrant muscle of the thigh.
CRINONE® 8% (Progesterone Vaginal Gel)
Progesterone 90 mg/dose, 8.0 % w/w. Each applicator contains 1.45 g of gel and delivers 1.125g 8% gel.
The progesterone vaginal gel is based on a polycarbophil delivery system which attaches to the vaginal mucosa and provides a prolonged release of progesterone for at least three days.
List of inactive substance used as a carrier for the active ingredients:
Light Liquid Paraffin,
Hydrogenated Palm Oil Glyceride,
Shelf life: 36 months.
How does Crinone 8% work?
Crinone 8% comes in the form of a bioadhesive gel. This gel is squeezed from an applicator into the vagina. Once in the vagina, the gel attaches to the vaginal wall, enabling patients to stand and go about their normal routine immediately after application, where progesterone is absorbed and transported to the uterus. Even if the applicator is not inserted all the way to the cervix, gently squeezing the bulb will direct the gel towards the cervix. The applicator is designed to deliver the correct amount of gel with a gentle squeeze. A small amount of gel will be left in the applicator after administration. This is normal. In addition, normal movement between the vaginal walls will spread the gel.
Crinone 8% should not be applied at the same time as other local vaginal treatments. If other local intravaginal therapy is to be used, it should be administered at least 6 hours before or after Crinone 8% administration.
Regular sexual activity has not been found to lessen the effectiveness of the drug.
Crinone 8% should not be used by women who have:
• Allergies to progesterone, progesterone-like drugs, or any of the inactive ingredients in the gel
• Undiagnosed vaginal bleeding
• Liver dysfunction or disease
• Known or suspected cancer of the breast or genital organs
• Had a missed abortion (i.e. a miscarriage in which the gestational tissue remains in the uterus)
• A history of or active thrombophlebitis or thromboembolic disorders
Before using Crinone Gel inform your physicians about:
If you are pregnant, planning to become pregnant, or are breast-feeding
If you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
If you have allergies to medicines, foods, or other substances
If you have heart or blood vessel problems, bleeding problems, high blood pressure, high cholesterol or lipid levels, diabetes, kidney problems, asthma, migraine headaches, or lupus
If you have a history of seizures, depression or other mental/mood problems, cancer, or tobacco use
If you have a family history of blood clots
If you are very overweight
Medication interaction with Crinone Gel.
Tell your health care provider if you are taking any other medicines, especially any of the following:
Rifampin because it may decrease Crinone Gel’s effectiveness
Storage or handling care
Crinone 8% should be stored between 59° and 86°F (15° and 30°C).
Do not expose Crinone 8% to extreme cold or heat.
Crinone 8% does not require refrigeration or other special care.
Important Safety Information
The most common side effects of Crinone 8% include:
Crinone 8% is contraindicated in patients with active thrombophlebitis or thromboembolic disorders, or a history of hormone-associated thrombophlebitis or thromboembolic disorders, missed abortion, undiagnosed vaginal bleeding, liver dysfunction or disease, and known or suspected malignancy of the breast or genital organs.
How to use Crinone
Crinone comes in a slim, rounded vaginal applicator that is similar to a tampon applicator. Some gel will be left over in the applicator after use.
Here are step-by-step instructions for taking Crinone 8%:
Wash your hands thoroughly and make sure that the surface you work on is clean.
Each prefilled applicator of Crinone comes individually wrapped within the Crinone box.
Carefully remove the wrapper from the prefilled applicator.
Identify the thick end of the applicator. Grasp the applicator by the thick end but do not squeeze yet.
With your other hand, grasp and bend the tab located at the opposite end of the applicator. Bend and twist the tab until it breaks away from the applicator.
Choose a comfortable position for inserting the applicator. You may lay on your back
You may stand
Insert the applicator into the vagina as far as it will comfortably go or when one half of the applicator has been inserted whichever is less.
Squeeze the bubble and the thick end completely. An amount of gel about the size of a dime will be dispensed into the vagina.
Remove the applicator. The gel will remain in the vaigna. Dispose of the used applicator. Do not reuse the applicator. If you wish, you may remove the residual gel by inserting your finger into the vagina and clearing the gel manually.
Progesterone in capsules – Utrogestan (Prometrium)
Each capsule contains 200mg micronised progesterone as the active substance.
Capsule contents: Arachis (peanut) oil, soybean lecithin.
Capsule shell: Gelatin, glycerol, titanium dioxide
UTROGESTAN 200mg capsules can be taken orally (should not be taken with food), and can be inserted into the vagina.
Do not take Utrogestan 200mg Capsules if:
• You are allergic to progesterone or any of the other ingredients in this product
• If you are allergic to peanut or soya as Utrogestan 200mg Capsules contain arachis oil (peanut oil)
• You have severe liver disease
• You have, or have had, breast cancer
• You have porphyria (a metabolic disease resulting in abnormal colouring in the urine and the skin)
• You have had blood clots, bleeding of the brain, or a stroke.
Take special care with Utrogestan 200mg Capsules if:
• You have high blood pressure, a heart, kidney or liver disease
• You suffer from epilepsy, diabetes, migraine or asthma
• You suffer from depression, or have had depression in the past
• Your skin is sensitive to light (photosensitivity)
• You are taking medicines containing bromocriptine, cyclosporin, rifamycin or ketoconazole. If you are not sure check with your doctor.
• If unexplained, sudden or gradual, partial or complete loss of vision, proptosis or diplopia, papilloedema, retinal vascular lesions or migraine occur during therapy, the drug should be discontinued and appropriate diagnostic and therapeutic measures instituted.
• Utrogestan 200mg Capsules should be used cautiously in patients with conditions that might be aggravated by fluid retention (e.g. hypertension, cardiac disease, renal disease, epilepsy, migraine, asthma); in patients with a history of depression, diabetes, mild to moderate hepatic dysfunction, migraine or photosensitivity and in breast-feeding mothers.
Symptoms of overdosage may include:
Euphoria or dysmenorrhoea.
Micronised progesterone is absorbed by the digestive tract. Pharmacokinetic studies conducted in healthy volunteers have shown that after oral administration of 2 capsules (200mg), plasma progesterone levels increased to reach the Cmax of 13.8ng/ml +/- 2.9ng/ml in 2.2 +/- 1.4 hours. The elimination half-life observed was 16.8+/- 2.3 hours.
Progesterone is approximately 96%-99% bound to serum proteins, primarily to serum albumin (50%-54%) and transcortin (43%-48%).
Urinary elimination is observed for 95% in the form of glycuroconjugated metabolites, mainly 3 α, 5 β–pregnanediol (pregnandiol).
Progesterone is metabolised primarily by the liver. The main plasma metabolites are 20 α hydroxy- Δ 4 α- prenolone and 5 α-dihydroprogesterone. Some progesterone metabolites are excreted in the bile and these may be deconjugated and further metabolised in the gut via reduction, dehydroxylation and epimerisation. The main plasma and urinary metabolites are similar to those found during the physiological secretion of the corpus luteum
Shelf life: 3 years
Storage: No special precautions for storage.
Endometrin (progesterone) Vaginal Insert 100 Mg is a brand of micronized progesterone inserts, supplied with polyethylene vaginal applicators.
The chemical name for progesterone is pregn-4-ene-3,20-dione. It has an empirical formula of C21H30O2 and a molecular weight of 314.5. Progesterone exists in two polymorphic forms. The form used in Endometrin, the alpha-form, has a melting point of 127-131°C.
Inactive Ingredients include:
Sodium lauryl sulfate
Collodial silicone dioxide.
Dosage and administration
The dose of Endometrin is 100 mg administered vaginally two or three times daily
Do not take if:
• Previous allergic reactions to progesterone or any of the ingredients of Endometrin Vaginal Insert
• Known missed abortion or ectopic pregnancy
• Liver disease
• Known or suspected breast cancer
• Active arterial or venous thromboembolism or severe thrombophlebitis, or a history of these events
The most common adverse reactions reported (greater than 2 %) were:
• Post-oocyte retrieval pain
• Abdominal pain
No formal drug-drug interaction studies have been conducted for Endometrin
Endometrin is not recommended for use with other vaginal products (such as antifungal products) as this may alter progesterone release and absorption from the vaginal insert
Storage or handling care
Endometrin should be stored between 59° and 86°F (15° and 30°C).
How to use the drug:
Follow the steps below:
Unwrap the applicator.
Put one insert in the space provided at the end of the applicator. The insert should fit snugly and not fall out.
Place applicator with the insert into the vagina while you are standing, sitting, or when lying on your back with your knees bent. Gently place the thin end of the applicator well into the vagina.
Push the plunger to release the insert.
Remove the applicator and throw it away in the trash.
Other information for using Endometrin
• If you forget a dose of Endometrin, take the dose as soon as you remember, but do not use more than your daily dose.
• Call your doctor if you use too much Endometrin.
• Do not use any other vaginal products when you are using Endometrin.
• Progesterone can increase your chance of getting blood clots. Blood clots can be serious and lead to death.
Serious blood clots include those in the:
Lungs (pulmonary embolus)
Heart (heart attack)
Call your doctor or get medical help right away if you have:
Persistent pain in the lower leg (calf)
Sudden shortness of breath
Coughing up blood
Sudden blindness, partial or complete
Severe chest pain
Sudden, severe headache, vomiting, dizziness, or fainting
Weakness in an arm or leg, or trouble speaking
Yellowing of the skin and/or white of the eyes indicating possible liver problem
Other risks of progesterone use include:
Bloating or fluid retention
Mood swings and depression