Levonorgestrel-Releasing Intrauterine System - An Overview

Overview:

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a safe, effective, and acceptable form of contraception used to prevent pregnancy. It is also used for various non-contraceptive benefits, such as treatment for menorrhagia, endometriosis, and endometrial hyperplasia. The Levonorgestrel-releasing intrauterine system has also been used in combination with estrogen for hormone replacement therapy and as an alternative to hysterectomy.

Dosage and Administration:

The intrauterine system consists of 52 milligrams of Levonorgestrel. Initially, Levonorgestrel is released at approximately 20 micrograms per day. This rate then decreases progressively to approximately 11 micrograms per day after 5 years and 8 micrograms per day after 7 years.

Warnings:

1. Ectopic Pregnancy- If a patient becomes pregnant with the intrauterine system (IUS) in place, the likelihood of a pregnancy being ectopic is increased.

2. Intrauterine Pregnancy- If pregnancy occurs while using UID, it should be removed because leaving it in place may increase the risk of spontaneous abortion and preterm labor.

3. Septic Abortion- In patients becoming pregnant while using IUS, septic abortion with septicemia, septic shock, and death can also occur.

4. Pelvic Inflammatory Disease (PID)- IUS is contraindicated in the presence of known or suspected pelvic inflammatory disease or in women with a history of PID unless there has been a subsequent intrauterine pregnancy.

5. Perforation- Perforation in the uterine wall or cervix may occur, mostly during insertion, although the perforation may go undetected for some time.

6. Expulsion- Partial or complete expulsion of the IUS may occur, resulting in the loss of efficacy. Expulsion can also be associated with symptoms of pain or bleeding, or it can be asymptomatic and go unnoticed. IUS typically decreases menstrual bleeding over time; hence, an increase in menstrual bleeding may indicate an expulsion.

7. Ovarian Cysts- The contraceptive effect of IUS is mainly due to its local effects within the uterus. Ovulatory cycles with follicular rupture can occur in women of fertile age using IUS. Most cysts are asymptomatic, but some may be accompanied by pelvic pain or dyspareunia. In most cases, the cysts disappear within two to three months.

8. Bleeding Pattern Alterations- IUS can alter the bleeding pattern and result in spotting, irregular and heavy bleeding, oligomenorrhea, and amenorrhea.

9. Breast Cancer- Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception, including Levonorgestrel-releasing IUS because some breast cancers are hormone-sensitive.

Use in Specific Population:

1. Pregnancy- The Levonorgestrel-releasing intrauterine system is contraindicated in pregnancy or with a suspected pregnancy as it may cause adverse pregnancy outcomes.

2. Lactation- Studies have reported the presence of Levonorgestrel in human milk, but There are no reports of adverse effects in breastfed infants. A few cases have reported decreased milk production in lactating mothers. The overall health benefit of the infant and the mother should be considered before administering Levonorgestrel-releasing IUS.

3. Pediatric Use- The safety and efficacy of Levonorgestrel-releasing IUS have been established in women of reproductive age. Use of this product before menarche (first occurrence of periods) is not indicated.

4. Geriatric Use- Levonorgestrel releasing IUS has not been studied in women over 65 years and is not approved for use in this population.

For Patients:

What Is Contraception?

Contraception, also known as birth control, is a way to prevent pregnancy. There are various methods of contraception that come in the form of pills, condoms,implants, injectables, patches, vaginal rings, Intra uterine devices, and male and female sterilization. Some of these are reversible, and some can be permanent.

• Barrier Methods- Condoms, contraceptive sponge, spermicide, diaphragm, and cervical cap.
• Hormonal Methods- Oral contraceptive, contraceptive patch, vaginal ring, injectable birth control, implant.
• Devices- Intrauterine devices.
• Sterilization- Tubal ligation, vasectomy.

Why Is Levonorgestrel-Releasing Intrauterine System Prescribed?

The Levonorgestrel-releasing intrauterine system is a contraceptive device that contains the female hormone- Levonorgestrel. It is placed inside the uterus (womb), where it slowly releases the hormone to prevent pregnancy for up to three to eight years, depending on the brand used. It works by stopping the female’s egg from fully developing every month. The egg can no longer accept sperm, and pregnancy is prevented. The Levonorgestrel-releasing intrauterine system is also used for treating heavy menstrual bleeding for up to five years in females. This medication is given only by or under the supervision of a doctor.

How Levonorgestrel-Releasing Intrauterine System Should Be Used?

The levonorgestrel intrauterine system is a small, flexible, T-shaped plastic device that a doctor inserts into the uterus. It can be used for three to eight years, depending on the patient’s wish and the brand of the medication. If a patient wishes to continue using the intrauterine system to prevent pregnancy after time has passed, the doctor will insert a new one, and the old one will be removed. The intrauterine system can be removed by a doctor any time the patient wants to become pregnant or want to use a different form of birth control.

There are the following things that need to be considered when opting for this system, that include-

• The doctor will advise the best time to insert the Levonorgestrel intrauterine system. Depending on the timing, one may need to use a non-hormonal birth control method such as condoms and spermicide for seven days to prevent pregnancy if sexual intercourse occurs.

• The intrauterine system can also be inserted immediately after a first-trimester miscarriage or abortion.

• If a person has given birth, had a miscarriage, or had a second-trimester abortion. The intrauterine system should not be inserted until at least six weeks, and a physical exam should be done to determine that the uterus has recovered from the pregnancy.

• The intrauterine system should be inserted in a healthcare provider's office or clinic.

• The doctor may advise taking a pain reliever before the appointment to help decrease cramping during and after the placement.

• Some people can experience symptoms during and after the placement, such as cramping, sweating, fast heartbeat, pale skin, fainting, dizziness, and bleeding. Inform the doctor if the cramping is severe or if these symptoms last longer than 30 minutes. The doctor will check to ensure that the system has been placed correctly.

• Contact the doctor if someone experiences severe pain during the first few hours after the intrauterine system is inserted. This can be a sign of a serious infection.

• The doctor will place the intrauterine system into the uterus and leave two threads dangling through the cervix. one should check for these threads once a month to ensure whether the intrauterine system is still in place. To check for the threads, one should wash hands with soap and water first and then reach up to the top of the vagina with clean fingers to feel the threads. If one cannot feel the threads or any part of the intrauterine system other than the threads, it can be a sign that the intrauterine system may not be in place and may not prevent pregnancy. If this happens, the consulting doctor should be contacted immediately.

• The patient will need a follow-up appointment with the doctor four to six weeks after the intrauterine system is inserted to ensure that the system is properly in place. After this appointment, patients will need to be examined once a year or more often if they have any problems or concerns.

• If the Levonorgestrel intrauterine system is to be removed, consult the doctor about the best time to remove it.

• The patient is not protected from pregnancy once the intrauterine system is removed, so if someone does not want to become pregnant, they need to be sure that they take effective birth control as soon as the intrauterine system is removed.

• If someone is planning to replace the intrauterine system with a new intrauterine system, they can have the old system removed, and the new system will be inserted at any time during the patient’s menstrual cycle.

• If someone chooses to use a different form of birth control instead of the intrauterine system and has regular menstrual cycles, they need to remove the system during the first seven days after their menstrual period begins and then start using the new form of birth control right away.

• If someone chooses to use a different form of birth control but does not have regular cycles, or does not menstruate at all, or is not able to have the intrauterine system removed during the first seven days of the menstrual period, then they should start using a new form of birth control seven days before the intrauterine system is removed.

What Special Precautions Should Be Taken?

• It is important to inform the doctor if the patient is allergic to Levonorgestrel or any other medication or any material that is being used to make Levonorgestrel.

• The doctor should be informed about any prescription or non-prescription medication the patient takes, especially those who take blood thinners. Any herbal products, dietary supplements, and nutritional supplements should also be informed.

• Medical conditions like breast cancer or any condition that affects the shape of the inside of the uterus, including fibroids, unexplained abnormal vaginal bleeding, cancer of the uterus or cervix, an untreated infection of the vagina or cervix, pelvic inflammatory disease, or any condition that affects the immune system such as leukemia, an acquired immunodeficiency syndrome (AIDS), liver disease or a tumor of the liver should be informed to the doctor.

• Any serious infection after pregnancy or abortion in the past three months should also be mentioned.

• If someone has had a pelvic inflammatory disease in the past and has not had a normal pregnancy since the PID got better, or if someone injects street drugs, has more than one sexual partner, or the partner of the patient has more than one sexual partner. The doctor may advise not to use a Levonorgestrel intrauterine system.

• If the patient ever had a stroke, heart attack, ectopic pregnancy, surgery to treat any problem, fallopian tubes, or abnormal pap smear should be informed to the doctor.

• If the patient experiences a slow heartbeat, or develop heart disease, heart valve disease, high blood pressure, or any condition that can cause fainting, severe headaches or migraines, blood clotting problem, or seizures, then it should be informed to the doctor.

• If a patient already has an intrauterine system inserted, it should be mentioned to the doctor.

• If someone is pregnant or planning to get pregnant, they should not use the Levonorgestrel intrauterine system. A doctor will ask the patient to get a pregnancy test before placing the intrauterine system in case the patient is pregnant.

• One should also know about the risks of becoming pregnant even when they have an intrauterine system. It is unlikely that the patient will become pregnant while the intrauterine system is in place, but the chances of becoming pregnant are there. There is a risk that the pregnancy can be ectopic. Ectopic pregnancies can be life-threatening and cause internal bleeding or loss of fertility.

• If the pregnancy is not ectopic, there is a risk that the patient can develop a severe infection, miscarriage, begin to labor prematurely or die if the pregnancy continues with the intrauterine system in place.

• If a patient becomes pregnant with a Levonorgestrel intrauterine system, the risks of removing the system should be discussed with the doctor. If the patient continues the pregnancy with the intrauterine system in place, it will increase the risk of miscarriage or infection.

• The patient will need to see the doctor often and call immediately if they develop signs of pregnancy, loss, or infection, including flu-like symptoms like fever, chills, cramping, pain, bleeding, vaginal discharge, or leaking.

• Contact the consulting doctor immediately if the patient thinks they may become pregnant or experience symptoms of ectopic pregnancy, such as unusual vaginal bleeding or pain in the stomach area at any time while the intrauterine system is in place.

• Breastfeeding patients can use the Levonorgestrel intrauterine system if breastfeeding is more than six weeks after giving birth.

• Changes in the menstrual cycle, while the intrauterine system is in place, can be expected. periods may become irregular or longer and can be heavier than usual during the first three to six months after the intrauterine system is inserted. Patients may experience spotting or light bleeding between periods during this time. As time passes, periods may become lighter and shorter or stop completely. If the period stops completely, it will return when the intrauterine system is removed. Contact the consulting doctor if periods do not come in six weeks or if the bleeding has become light for a time but becomes heavy.

• The intrauterine system cannot be felt during sexual intercourse because the system will be placed inside the uterus. However, the patient’s partner may feel the threads. Contact the doctor if this happens.

• There is a risk that the intrauterine system will become attached to the wall of the uterus or may move through the wall of the uterus, causing damage or scarring to other organs. If this happens, the patient might need surgery to remove the system. There is a higher risk that the intrauterine system will move through the wall of the uterus if the patient is breastfeeding.

• Levonorgestrel intrauterine system may increase the risk of developing pelvic inflammatory disease (PID), which may cause infertility, ectopic pregnancy, pain that does not go away, and even death. PID must be treated with surgery, including a hysterectomy (surgery to remove the uterus). The risk of developing PID is higher if the patient or their partner has more than one sexual partner. Contact the doctor if any symptoms of PID occur, such as painful sex, long-lasting or heavy bleeding, unusual vaginal discharge, stomach-area pain, fever, and chills.

What Are the Side effects of the Levonorgestrel Intrauterine System?

Levonorgestrel intrauterine system may increase the risk of developing cysts on the ovary. This cyst can cause pain but usually disappears in two to three months. In rare cases, surgery might be needed to remove the cyst.

Other side effects include -

• Headaches.

• Nausea.

• Cramps or pain during menstruation.

• Acne.

• Breast tenderness.

• Weight gain.

• Decreased sexual desire.

• Changes in mood.

• Depression.

• Hair loss.

• Unwanted hair growth.

• Yellowing of the skin or eyes.

• Drooping of one side of the face.

• Swelling of the lips, tongue, throat, arms, hands, legs, or feet.

• Rashes.

• Hives.

• Foul-smelling or unusual vaginal discharge.

• Vaginal pain.

• Pain during sex.

• Sores on the genital area.

• Sudden weakness of an arm or leg.

• Difficulty speaking or understanding.

• Crushing chest or shoulder pain.

Other Information:

• Before going for a magnetic resonance imaging (MRI scan), it is important to inform the doctor and the radiology staff that an intrauterine system has been inserted in the patient.

• A written list of all the prescription and non-prescription medications that the patient takes should be kept and brought to each appointment with the doctor. It is advisable to carry the list in case of emergencies.

For Doctors:

Indications-

Levonorgestrel releasing intrauterine system is used to prevent pregnancy. It is also indicated for heavy menstrual bleeding. It can be used for uterine fibroids, endometriosis, adenomyosis, and endometrial hyperplasia.

Mechanism of Action:

The mechanisms of action of the Levonorgestrel-releasing intrauterine system are similar to that of Levonorgestrel implants or Levonorgestrel-containing mini-pills. However, it accomplishes these effects with much lower peak serum levels than other progestin-containing contraceptives. The Levonorgestrel-releasing intrauterine system is a T-shaped device composed of a cylinder containing 52 milligrams of Levonorgestrel covered by a rate-controlling membrane that regulates the rate of hormonal release.

Initially, 20 micrograms of Levonorgestrel are released every 24 hours from this polymer cylinder, which then decreases to 11 micrograms every 24 hours by the end of five years, with an average release rate of 14 micrograms per day over the life of the intrauterine system. Levonorgestrel is a highly potent second-generation progestin that thickens cervical mucus and suppresses endometrial proliferation. This creates a hostile environment for sperm survival, inhibiting motility and capacitation with the net effect combining to prevent fertilization.

Pharmacodynamics:

The local concentrations of Levonorgestrel lead to morphological changes, including stromal pseudodecidualization, glandular atrophy, leukocytic infiltration, and a decrease in glandular and stromal mitoses.

Pharmacokinetics:

• Absorption- A stable serum concentration, without peaks and troughs, of Levonorgestrel of 150 to 200 picograms per milliliter occurs after the first few weeks following insertion of IUS.

• Distribution- The apparent volume of distribution of Levonorgestrel is reported to be approximately 1.8 liters per kilogram. It is approximately 97.5 to 99 percent protein-bound, principally to sex hormone-binding globulin (SHBG) and, to a lesser extent, serum albumin.

• Metabolism- Levonorgestrel is conjugated at the 17 beta-OH positions to form sulfate conjugates and, to a lesser extent, glucuronide conjugates in serum. Significant amounts of conjugated and unconjugated 3-alpha, 5 beta-tetrahydro Levonorgestrel are also present in serum, along with much smaller amounts of 3 alpha, 5 alpha tetrahydro levonorgestrel, and 16 beta hydroxylevonorgestrel. Levonorgestrel and its phase I metabolites are excreted mainly as glucuronide conjugates. Metabolic clearance rates may differ among individuals several-fold, and this may account in part for wide variations in Levonorgestrel concentrations seen in individuals using containing contraceptive products. In vitro studies have demonstrated that the oxidative metabolism of Levonorgestrel is catalyzed by CYP enzymes, especially CYP3A4.

• Excretion- About 45 percent of Levonorgestrel and its metabolites are excreted in the urine, and about 32 percent are excreted in feces, mostly as glucuronide conjugates. The elimination half-life of Levonorgestrel is approximately 17 hours after daily oral doses.

Administration:

• Obtain a complete medical and social history of the patient to determine conditions that might influence the selection of a levonorgestrel-releasing intrauterine system for contraception.

• If required, perform a physical examination and do appropriate tests for any signs of genital or other sexually transmitted infections.

• Since irregular bleeding or spotting is common during the first months of intrauterine system use, exclude endometrial pathology (polyps or cancer) before IUS is inserted in women with persistent or uncharacteristic bleeding.

• Follow the insertion instructions as described in the package to ensure proper placement and avoid premature release of Levonorgestrel from the inserter. Once released, it cannot be re-loaded.

• Check the expiration date of the product before initiating insertion.

• The IUS should be inserted by a trained healthcare professional, who should become thoroughly familiar with the insertion instructions before attempting to insert the IUS.

• Insertion may be associated with pain, bleeding, vasovagal reactions (syncope or bradycardia), or seizure, especially in patients with a predisposition to these conditions. Consider administering analgesics before insertion.

Preparation for Insertion:

• Check for pregnancy and ensure no other contraindications to using the Levonorgestrel-releasing intrauterine system.

• Lie down the patient comfortably in the lithotomy position and perform a bimanual exam to determine the size, shape, and position of the uterus.

• Gently and slowly insert a speculum to visualize the cervix.

• Thoroughly clean the cervix and vagina with an antiseptic solution.

• Prepare to sound the uterine cavity. Grasp the upper lip of the cervix with tenaculum forceps and gently apply traction to stabilize and align the cervical canal with the uterine cavity. Perform a paracervical block if needed. If the uterus is tilted abnormally backward, it is more appropriate to grasp the lower lip of the cervix. The tenaculum should remain in its position, and then maintain gentle traction on the cervix throughout the insertion.

• Gently insert a uterine sound to check the patency of the cervix and measure the depth of the uterine cavity in centimeters, confirm the cavity direction, and check the presence of any uterine anomaly. If any difficulty or cervical stenosis is encountered, use dilatation, and do not force to overcome resistance. If cervical dilatation is needed, consider using a paracervical block.

• The uterus should sound to a depth of six to ten centimeters. Inserting IUS into a uterine cavity less than six centimeters by sounding may increase the incidence of expulsion, bleeding, pain, perforation, and possibly pregnancy.

Insertion Procedure:

• Open the package using sterile gloves, lift the handle of the sterile inserter, and remove it from the sterile package.

• Push the slider forward as far as possible in the direction of the arrow, and move the insertion tube over the IUS T-body to load Levonorgestrel into the insertion tube. The tips of the arms should meet and form a rounded end that extends slightly beyond the insertion tube.

• Maintain forward pressure with thumb or forefinger on the slider. Caution should be taken to not move the slider downward at this time, as this may prematurely release the threads of the IUS. Levonorgestrel cannot be re-loaded once the slider is moved below the mark.

• Hold the slider in this forward position, and set the upper edge of the flange to correspond to the uterine depth, measured during sounding.

• Continue holding the slider in this forward position and advance the inserter through the cervix until the flange is approximately 1.5 to 2 centimeters from the cervix, and then pause.

• Hold the inserter steady, and move the slider down to the mark to release the arms of the Levonorgestrel. Wait for 10 seconds for the horizontal arms to open completely.

• Advance the inserter slowly and gently towards the fundus of the uterus until the flange touches the cervix. If there is fundal resistance, do not continue to advance. Now Levonorgestrel is in the fundal position. The fundal position of the IUS is important to prevent expulsion.

• Next, hold the entire inserter firmly in place and release levonorgestrel by moving the slider all the way down.

• Continue holding the slider all the way down and slowly and gently withdraw the inserter from the uterus.

• Use a sharp and curved scissor to cut the threads perpendicular, leaving about three centimeters of thread visible outside of the cervix. Do not apply tension or pull on the threads while cutting to prevent displacing the IUS.

• Prescribe analgesics, if required.

Other Considerations:

• If it is suspected that the IUS is not in the correct position, then check placement using transvaginal ultrasound.

• Remove the intrauterine system if it is not positioned completely within the uterus. Do not reinsert a removed IUS.

• If there is a clinical concern, such as pain or bleeding during or after the insertion, immediately take appropriate steps, such as physical examination and ultrasound, to exclude the chances of perforation.

• Follow-up patients four to six weeks after insertion and once a year or more frequently if indicated clinically.

Removal of Levonorgestrel Releasing Intrauterine System:

• Remove the intrauterine system by applying gentle traction on the threads using forceps.

• If the threads are not visible, determine the location of the IUS by ultrasound.

• If IUS is found in the uterine cavity on ultrasound exam, it can be removed by using narrow forceps like alligator forceps. This may require dilation of the cervical canal. After the removal of the IUS, examine the system to ensure that it is intact.

• Removal may be associated with pain and bleeding, vasovagal reactions, syncope, bradycardia, or seizure, especially in patients predisposed to these conditions.

• Breakage or embedment of IUS in the myometrium can make removal difficult.

Storage and Handling:

• Levonorgestrel releasing intrauterine system is supplied sterile and is sterilized with ethylene oxide.

• Do not resterilize the product.

• It is for single use only.

• The product should not be used if the inner package is damaged or open.

• Insert before the expiration date shown on the label.

• Store at 25 degrees Celsius with excursions permitted between 15 to 30 degrees Celsius.

What Are the Adverse Effects of Levonosgestrel Releasing Intrauterine System?

• Acne.

• Back pain.

• Headache.

• Migraine.

• Breast pain.

• Abdominal or pelvic pain.

• Genital discharge.

• Amenorrhea.

• Vulvovaginitis.

• Dysmenorrhea.

• Female genital tract bleeding.

• Decreased uterine bleeding.

• Increased scheduled uterine bleeding.

• Unscheduled uterine bleeding.

• Depression.

• Benign ovarian cyst.