Contraception implantable contraceptives

As of 1994, there were approximately 47 progestin-containing contraceptive dmg formulations sold in the United States for use as oral contraceptives (Table 3). In addition, there are three nonoral contraceptive formulations containing progestins ie, one injectable (Depo-Provera), one as an intrauterine device (lUD) (Progestasert), and one implantable (Norplant). Of the oral formulations, all but two also contain an estrogen component, ethynylestradiol. 

A prolonged action/controlled release system developed to deUver levonorgestrel for contraceptive therapy involves implantation of a set of flexible closed capsules made of demethylsiloxane—methylvinyl—sdoxane copolymer (see Contraceptives). Each capsule measures 2.4 mm in diameter and 34 mm in length. A set of six such capsules is surgically implanted beneath the skin of the upper arm. These capsules are intended to be removed by the end of the fifth year after implantation. 

The currendy (ca 1992) marketed injectable and implantable contraceptives are designed to be effective for maximum periods of three months and five years, respectively. There is Htde evidence from programmatic or health reasons that an injectable formulation with a longer effective life span, eg, six months, would not be equally effective. The acceptabiUty and effectiveness of long-acting contraceptives may be determined by the means by which a community deUvers contraceptive products to the pubHc the active life of a product may be determined by economic rather than programmatic or health related factors. 

Implanted Contraceptives. Controlled release of contraceptive progestins also can be accompHshed by incorporating the dmg into an implantable cylinder or rod. The best known implant is Norplant, developed by the Population Council. Norplant is composed of six matchlike silastic cylinders with the progestogen levonorgestrel (11) incorporated on the inside of each cylinder. After implantation under the skin, the product can provide effective contraception for a period of five years (43,44). Since silastic is not biodegradable, the implant can be removed from a patient at any time. 

Implantable controlled release dmg deUvery systems, including Norplant and other contraceptive steroids ia siUcone-based devices, have been reviewed (91,92). 

Hormonal contraceptives belong to the most widely prescribed and most efficacious drugs that have a profound impact on western societies since their inauguration in the 1960s. In women, oral hormonal contraceptives are used to prevent fertilization or implantation in cases of unplanned pregnancies. Apart from these primary objectives, there are significant additional medical benefits contributing to a substantial improvement of reproductive health in women. 

As under most circumstances progesterone action will hold primacy over estrogenic effects, the cervical mucus, endometrium, and probably the fallopian tubes reflect progestational stimulation. The cervical mucus becomes thick and viscous and thus impervious to spermatozoa. The endometrium is in a state that is not receptive for implantation of a fertilized egg. Probably, the progestational impact on the secretory activity and peristalsis in the fallopian tubes also assists the general contraceptive effect. It is difficult, however, to assess the relative contribution of the various effects to the... 

Progestin-only contraceptives (Fig. 4) contain low-doses of progestins (e.g. 350 pg norethindrone or 75 pg norgestrel) that have to be administered daily without interruption. The lowest expected failure rate during the first year of use is 0.5%, while the typical failure rate amounts to 3%. Subdermal implants of norgestrel (216 mg) for sustained release provides for long-term (for up to 5 years) contraceptive effects characterized by failure rates of only 0.05%. Reliable contraception for 3 months can be achieved by an intramuscular injection of a crystalline suspension of 150 mg medroxyprogesterone acetate (Fig. 3) (failure rate 0.3%). 

In breast cancer patients, total PR status is measured for hormonal treatment. The presence of PR is associated with increased survival rates and hormonal responsiveness of mammary tumors. PR agonists are widely used in contraception, HRT, breast cancer, and endometrial hyperplasia. Antiprogestins such as RU486 are used for blocking ovulation and preventing implantation, and in addition they are in clinical testing for the induction of labor and to control various neoplastic transformations. 

Impiant Contraceptive Systems (Progestins) levonorgestrel 6 capsules, each containing 36 mg levonorgestrel for subdermal implantation... 

IMPLANT CONTRACEPTIVE SYSTEM. Levonorgestrel, a progestin, is available as an implant contraceptive system (Norplant System). Six capsules, each containing levonorgestrel, are implanted under local anestiiesia in die subdermal (below the skin) tissues of the mid-portion of die upper arm. The capsules provide contraceptive protection for 5 years but may be removed at any time at die request of the patient. See Table 52-3 for more information on ways to promote an optimal response when taking die contraceptive hormones. 

All devices used for contraception or the prevention of the transmission of sexually transmitted diseases are in Class lib, unless they are implantable or long-term Invasive devices, in which case they are in Class III. 

The first documented use of sUicone as biomaterial was silicone mbber tubing as shunts for treatment of hydrocephalus in about 1955. From 1960 to 1990, the biomedical application of sUicone mbber was steadUy grown. One of the most well-known silicone product is the Norplant contraceptive implant. The first clinical experiment with this device was reported in 1966. FDA approved its use in 1990. 

Segal, S., Contraceptive subdermal implants, in Advances in Fertility Research (D. R. Mishell, ed.). Raven Press, New York, 1982, pp. 117-137. 

The development of a bioerodible implant capable of releasing controlled amounts of a contraceptive steriod from a subcutaneous implant for periods of time ranging from three months to about a year has been in progress for many years. The three principal bioerodible polymers currently in use are copolymers of lactic and glycolic acid (25), poly(e-caprolactone) (26), and poly (ortho esters) (14). The desire to develop such a contraceptive system was the principal motivation for the initial development of the poly(ortho ester) polymer system. 

Based on these studies, it is obvious that poly(N-acylhydroxy-proline esters) are very slowly degrading polymers. These materials may therefore be useful for long-term applications, such as implantable, multiyear contraceptive formulations. For such applications the degradation rates of poly (lactic acid)/poly (glycolic acid) devices would probably be too rapid. 

Although suppression of FSH and LH is the primary mechanism by which combined oral contraceptives prevent ovulation, there are other mechanisms by which these hormones work to prevent pregnancy. Other mechanisms include reduced penetration of the egg by sperm, reduced implantation of fertilized eggs, thickening of cervical mucus to prevent sperm penetration into the upper genital tract, and slowed tubal motility, which may delay transport of sperm.1 Thus, in... 

Contraception is the prevention of pregnancy following sexual intercourse by inhibiting sperm from reaching a mature ovum (i.e., methods that act as barriers or prevent ovulation) or by preventing a fertilized ovum from implanting in the endometrium (i.e., mechanisms that create an unfavorable uterine environment). 

Women who particularly benefit from progestin-only methods, including minipills, are those who are breast-feeding, those who are intolerant to estrogens, and those with concomitant medical conditions in which estrogen is not recommended. Also injectable and implantable contraceptives are beneficial for women with compliance issues. 

It is through the local generation of eicosanoids that intrauterine contraceptive devices are effective, since they stimulate production of prostaglandins by the myometrium which increases its contractility, preventing implantation. 

Contraception is the prevention of conception by a variety of means. Only hnmans actively seek to avoid fertilisation and/or implantation of the embryo (except for animals in which a male attempts to achieve paternity by preventing subsequent mating). 

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