What Are the Pros and Cons of Contraceptive Injections?

Long-acting contraceptives are drugs used to inhibit ovulation and prevent implantation. Its advantages are high efficiency, long-acting, reversible, no daily medication, easy to use and distribute, and does not affect sexual life. However, it also has disadvantages. After taking long-acting contraceptives, some women will increase their menstrual flow, prolong their menstrual periods, and may cause amenorrhea.

Long-acting contraceptives are drugs used to inhibit ovulation and prevent implantation. Its advantages are high efficiency, long-acting, reversible, no daily medication, easy to use and distribute, and does not affect sexual life. However, it also has disadvantages. After taking long-acting contraceptives, some women will increase their menstrual flow, prolong their menstrual periods, and may cause amenorrhea.

Drug Name

Long-acting contraceptive

Dosage

1

Adverse reactions

Increased nausea and vomiting secretions

Advantages

Efficient and long-lasting reversible

Missing point

Increased menstrual periods and prolonged amenorrhea

Long-acting contraceptives

Compared with short-acting contraceptives, long-acting contraceptives do not need to be administered daily, and the drug is slowly and constantly released in the body after one administration, maintaining long-acting and highly effective contraceptive effects, which can improve user compliance and satisfaction, and are easy to use And distribution, does not affect sexual life, significantly reduces accidental pregnancy.

Long-acting contraceptives

Some women use long-acting contraceptives, their menstrual flow will increase, their periods will prolong, and they may cause amenorrhea. In terms of chemical composition, long-acting contraceptives are similar to short-acting contraceptives, and can be divided into three types: estrogen, progesterone and estrogen-pregnancy mixture. Because long-acting drugs need to be put into the body at one time, the amount is relatively large, and there may be a certain accumulation after stopping the drug. Therefore, under normal circumstances, women who have not given birth are best not to take long-acting contraceptives. If you want to have a baby after taking the medicine, you should stop taking the medicine for 3 months to 6 months ^[1] .

Long -acting contraceptives

1. Levonorgestrel Estradiol Tablets

Dosage

1. From the day of menstruation, take the medicine once on lunch on the fifth day, take the second medicine every 20 days, or take one tablet on the fifth and tenth days of menstruation, and then use the second medicine date every month. Take 1 tablet, usually with withdrawal bleeding 6 to 12 days after taking the medicine. If the adverse reaction is serious after taking the medicine, the dosage reduction tablet can be switched to the fourth cycle. 2. When taking a short-acting oral contraceptive and changing to a long-acting contraceptive, you can take the long-acting contraceptive pill the next day after taking 22 tablets, and then take the same medication every month on the same date as the long-acting contraceptive. sheet.

[Pharmacological action]

Ethinylestradiol (ethinylestradiol) is a long-acting estrogen. It is absorbed through the gastrointestinal tract after oral administration and stored in adipose tissue. It slowly releases ethinylestradiol, which inhibits the ovary by inhibiting the hypothalamus-pituitary-ovarian axis. Ovulation achieves a long-acting contraceptive effect, and the compatibility of progestin with it can have a synergistic effect on the inhibition of ovulation, but also can transform the endometrium and present a secretion phenomenon, leading to withdrawal bleeding and periodic changes. Taking the medicine once a month, the contraception rate can reach more than 98%.

medicine interactions

1. Drugs that affect contraceptive effects: Antibiotics inhibit intestinal bacterial reproduction, reduce the breakdown of hormone conjugates, and reduce intestinal and liver circulation; drugs that induce liver drug enzymes such as rifampicin, hypnotics and anticonvulsants, antipyretics and analgesics Drugs; tricyclic antidepressants compete with this product for common metabolic enzymes in the liver. 2. Combined use with contraceptives, drugs with affected efficacy: reduced antihypertensive effect of antihypertensive drugs; reduced anticoagulant effect; reduced efficacy of diabetes-lowering drugs (such as insulin and oral hypoglycemic drugs) in controlling diabetes; tricyclic The effect of class antidepressants is enhanced.

Adverse reactions

1. Early pregnancy-like reactions: They behave similarly to short-acting oral contraceptives, but they are more serious. The performance of the first few cycles of the medication is heavier. The reaction usually occurs 8 to 12 hours after the medication. Therefore, the medication time is set after lunch. To make the reaction climax just in deep sleep can make it less. 2. Increased leucorrhea: the most common adverse effect of long-acting oral contraceptives. Mostly occur after 3 to 6 cycles. 3. A few people have menorrhagia or amenorrhea. 4. Others include stomach pain, edema, breast tenderness, and headache.

[Taboo]

Uterine fibroids, breast masses, liver and kidney dysfunction, cardiovascular disease, history of thrombosis, hypertension, diabetes, hyperthyroidism, psychosis or depression, hyperlipidemia patients are prohibited.

2. Etogestrel

Subcutaneous implants of etonogestrel for contraception, each containing 68 mg of etonogestrel, the effective rate of contraceptive over three years is over 99.5%. The operation process of the new implant is very simple, safe and reliable, and can be easily implanted and removed. The average implantation time is less than 1 minute, and no suture is required. You may become pregnant in the first week after removal.

[Pharmacological action]

This product is a single progestin subcutaneous implant. Its contraceptive effect is mainly achieved through the inhibition of ovulation on the pituitary-gonad axis. In addition, it can increase the viscosity of cervical mucus and prevent the penetration of sperm.

Each implant contains 68mg etonogestrel: the release rate is about 60-70µg / day within 5-6 weeks after implantation, it drops to about 35-45µg / day at the end of the first year, and drops to about 30- at the end of the second year 40µg / day, decreased to about 25-30µg / day at the end of the third year.

Instructions

This product is a long-acting contraceptive, which is implanted subcutaneously to provide a contraceptive effect for up to three years. The user can request the removal of the implant at any time, but the same implant cannot be implanted continuously for more than 3 years. For heavier women, clinicians may consider replacing implants early (see "Precautions"). Immediately after removing the implant, another implant is placed in order to continue receiving contraceptive protection. If you do not want to continue using this product, but still want to continue contraception, other contraceptive methods should be recommended.

This product should be implanted subcutaneously on the inside of the upper arm to avoid the large blood vessels and nerves deep in the connective tissue between the biceps and triceps muscles. Implants should be implanted only superficially under the skin. If implanted too deeply, nerve or blood vessel damage can occur. Too deep or incorrect implantation may result in paresthesia (nerve damage) and movement of the implant (caused by implantation into the fascia or muscle layer), and rare implantation errors into the blood vessels. In addition, implantation too deeply can make the implant inaccessible and make it difficult to locate and / or remove the implant.

The presence of the implant can be confirmed by direct touch after implantation. If this product has not been touched or if it is uncertain, it must be confirmed by other methods (see "How to implant this product"). Before confirming the existence of this product, a non-hormonal contraceptive method should be recommended.

medicine interactions

Interactions with hormonal contraceptives and other drugs can lead to bleeding and / or failed contraception. No specific interaction studies have been performed for this product. The interactions reported in the literature are as follows (mainly interactions with compound contraceptives and sometimes with progestin-only contraceptives):

Liver metabolism: Drugs that induce liver enzymes, especially cytochrome P450 enzymes, may interact with this product, resulting in increased clearance of sex hormones (such as phenytoin, phenobarbital, primetone, bosentan, carbamazepine Rifampicin, and possibly oxcarbazepine, topiramate, felbamate, griseofulvin, and the herb St. John's wort).

HIV proteases (eg, ritonavir, nelfinavir), non-nucleoside reverse transcriptase inhibitors (eg, nevirapine, efavirenz), and combinations thereof, have been reported to affect liver metabolism.

Women taking any of these drugs should use non-hormonal contraception in addition to this product. With liver enzyme-inducing drugs, other non-hormonal contraceptive methods should be taken simultaneously until 28 days after discontinuation.

For women taking liver enzyme-inducing drugs for a long time, it is recommended to take this product and use other non-hormonal contraceptive methods.

Drugs that increase plasma hormones: Drugs that inhibit liver enzymes (such as CYP3A4) (such as ketoconazole) may increase plasma hormone levels.

Long-acting contraceptives

Subcutaneous implant

A subcutaneous implant is a form of preparation that is implanted into the human subcutaneous tissue through surgery or a specific syringe. The main advantage is its long-acting effect, that is, the drug release period is as long as 3 to 5 years. It is often used for contraception, or to treat diseases such as tumors and chronic arthritis that require long-term administration. According to the nature of the carrier material, it can be divided into two types: biodegradable and non-biodegradable. The expiration period of the non-biodegradable subcutaneous implants needs to be taken out by surgical staff, which greatly restricts its application; while the carrier materials of the biodegradable subcutaneous implants eventually degrade into water and carbon dioxide in the body. No need to take out when full.

At present, all subcutaneous contraceptive implants on the market are non-biodegradable. Norplant, the first subcutaneous contraceptive implant, was launched in Finland for the first time. It consists of 6 silicone rubber tubes, each containing 36 mg of levonorgestrel (LNG), for 5 years of contraception. However, due to the tedious process of implantation and removal of six implants, two alternative silicone rubber tube implants, Norplant (), appeared, which released the same dose of LNG as Norplant, and the contraceptive time was the same.

Biodegradable subcutaneous implants have been completed in Phase II clinical studies as early as the 1990s, but so far no product has entered Phase III clinical studies. The single capsule LNG subcutaneous implant Capronor uses PCL (polycaprolactone) as a carrier material and is used for 1 year contraception.

Contraceptive injection

As far as drug delivery systems are concerned, contraceptive injections can be divided into oil solutions, microcrystalline suspensions, microspheres, and in situ gels, but currently there are limited products available. Only oil solutions and microcrystalline suspensions are effective. The contraceptive time is 1 to 3 months. Microspheres and in situ gel contraceptive injections are still in the preclinical stage.

Progestogen-only contraceptive injections mainly include heptarginone (trade name Norigest) and medroxyprogesterone acetate (trade name Depo-Provera). Depo-Provera (R) was approved by the FDA in 1992 and is the most commonly used contraceptive injection in the United States. However, it is accompanied by potential side effects of lowering bone density in young women. Therefore, it is recommended that it be administered in low doses. Young women should not use it for more than 2 years. It is reported in the literature that Depo-Provera and Norigest have no difference in contraceptive effects, but the former has frequent amenorrhea [39]. Compound contraceptive injections include products such as Deladroxate, Mesigyna and Cyclofem. Cyclofem is no longer sold in the United States, but is still widely used in Latin America and some parts of Asia. Deladroxate (R) contains high doses of hormones, especially estrogen, so there are safety issues. But compared with other low-dose estrogen products, Deladroxate (R) can better control the menstrual cycle.

Given that the contraceptive effects of currently available contraceptive injections are short and tolerance needs to be improved, improving these aspects can increase their use. Currently, clinical research on relevant microcrystalline suspensions is underway. LNG prodrugs are more fat-soluble than LNG and can prolong drug action time. Phase clinical studies have shown that a single dose of 50 mg of LNG prodrug microcrystalline suspension can inhibit female ovulation for 5 to 6 months. In particular, the overall toxicity, pharmacokinetics and pharmacodynamics of LNG-butyrate (LNG-B) showed good performance. At present, CONRAD is conducting clinical research on LNG-B microcrystalline suspension, with a view to obtaining a long-acting injection that can be used for 4 months as a contraceptive.

3. Transdermal contraceptives

Transdermal formulations are new dosage forms that are administered on the surface of the skin and the drug enters the systemic circulation through the skin at a constant rate to produce systemic or local therapeutic effects. It has all the advantages of non-oral administration, convenient administration and flexible medication. Transdermal formulations of hormonal drugs were first used for menopausal hormone replacement therapy and began to be used for contraception in the 1990s. Transdermal contraceptives can improve user compliance, maintain steady-state hormone levels, and maintain good menstrual patterns while providing contraception. However, due to the effect of transdermal efficiency, the amount of drug absorbed by the skin is only 10% of the total dose, and the contraceptive time is usually 1 week.

The first transdermal contraceptive patch, OrthoEvra, was launched in the United States in 2002, and was favored by many women. It was all the rage and achieved great commercial success. It contains 6mg of methyl progesterone (NGMN) and 0.75mgEE. It releases 150 g NGMN and 20 g EE, respectively, and the contraceptive failure rate is only 0.6%. The compliance and satisfaction of users are better than oral contraceptives. The second contraceptive patch, Evra, was launched in Canada for the first time; it was later sold in European countries and was also welcomed. Evra is similar in appearance to OrthoEvra, except that it contains only 0.6mgEE. OrthoEvra has a higher daily dose of estrogen and a potential high risk of venous thromboembolism. As a result, sales in the United States have gradually declined and it has now withdrawn from the US market, but Evra is still used in Canada and Europe.

The development of transdermal contraceptives for contraception is mainly aimed at continuously reducing the exposure of estrogen to reduce its potential adverse effects. AgileTherapeutic has developed a low-dose LNG and EE compound patch (trade name Twirla or AG200-15) containing 2.6 mg of LNG and 2.3 mg of EE. Among them, the daily release of EE is approximately equal to an oral contraceptive containing 30 g of EE. Phase and clinical studies have shown that Twirla's serum drug concentration is stable, the exposure dose of EE is low, the contraceptive effect is similar to that of the compound oral contraceptive, and the contraceptive effect is comparable in obese and normal weight users. A phase III clinical study is currently underway to further evaluate its compliance and contraceptive effects. BayerHealthCare has developed a low-dose GSD and EE compound patch containing 2.1 mg GSD and 0.55 mg EE. The patch significantly reduced the drug delivery dose of EE, releasing 57-66 g GSD and 19-23 g EE, respectively, each day. Phase III clinical studies have shown that its contraceptive effectiveness rate is 98.8% and the Pearl index is 0.81; the number of subjects with irregular or spotting bleeding decreased over time (11.4% for cycles1 and 6.8% for cycles12); tolerance Good compliance (average 97.9%, median 100%). In addition, a LNG-only contraceptive patch is undergoing a phase II clinical study to evaluate its effect on inhibiting ovulation and follicle size. The contraceptive patch releases a lower dose of LNG daily and is suitable for women who have contraindications to estrogen or are breastfeeding ^[2] .