O & G Forum | Volume 29 | Issue 1 | 2019

O&G Forum 2019; 29: 4 - 8 REVIEW Norman D Goldstuck Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, University of Stellenbosch, Cape Town, South Africa Abstract The development of slow release systems for parenteral delivery of progestins has transformed the range of available long-acting reversible contraceptives. The intrauterine route consists of three types of systems which differ in physical size and deliver different doses of levonorgestrel. There are two types of subdermal systems which release levonorgestrel and etonogestrel respectively. Release of both hormones largely obeys first order kinetics. Their contraceptive action is due to one or more actions which may include ovulation suppression, alteration of the characteristics of cervical mucus, atrophy and decidualization of the endometrium and alteration of tubal motility and cellular structure. While the subdermal implant has a lower pregnancy rate than the intrauterine system comparative studies favour the intrauterine route except shortly after pregnancy, miscarriage and medical and surgical termination of pregnancy when the risks of expelling the intrauterine system is elevated. In addition to contraception these actions may in certain circumstances provide therapeutic efficacy in dysmenorrhea, abnormal uterine bleeding, endometriosis, adenomyosis, leiomyomata, polyps, endometrial hyperplasia including tamoxifen induced adenomatous hyperplasia and certain stage 1 endometrial carcinomata. While there has been recent concern that all progestins may marginally increase the rate of breast cancer, there is evidence that they have protective effect against the development of endometrial, ovarian, colorectal, pancreatic and lung cancers. This may be due to progestin antagonizing the inflammatory products released during menstruation which has increased fourfold over the last 120 years. The benefits of parenteral progestins for the modern woman exceed the risks by a very wide margin for both pregnancy prevention and non- contraceptive benefits. Implants versus Intrauterine systems (IUSs) for delivery of progestins as contraceptives and therapeutics. Correspondence Norman Goldstuck email: nahumzh@gmail.com Introduction The intrauterine device (IUD) was introduced into medical practice by Richter in 1909 and refined by Ernst Grafenberg in Germany and the United States in the 1920’s. These early problematical devices were improved by Lippes in the US using thermoplastics in the 1960’s. Zipper and colleagues introduced copper as an anti-fertility agent in the I970’s and Luukainnen in Finland began using first progesterone and then levonorgestrel(LNG) to create what we now call the intrauterine system(IUS). The frame of the Nova-T © copper carrying IUD was used to hold a silastic slow release membrane containing 52 mg of LNG and was later marketed as Mirena © . 1 At about the same time the Population Council in New York began researching the use of subdermal LNG in a 6 rod system called Norplant © . This was later replaced by a two rod system with each rod containing 150 mg of LNG and was called Norplant-2 © and later marketed as Jadelle © . Organon , the Dutch pharmaceutical company began using the active ingredient of their third generation progestin, desorgestrel in a slow-release subdermal form in trials in the 1990’s. Merck bought Organon and now market this etonogestrel(ENG) containing implant as Implanon © . While the earlier IUDs were never called ‘Long- Acting Reversible Contraceptives (LARC)’, which they were, the term became entrenched after the introduction of the sub-dermal implants and was cemented after the demonstration of their unique continuing contraceptive efficacy particularly in the CHOICE project in St Louis, Missouri. For good measure the World Health Organisation(WHO) has added injectables to the LARC bandwagon. This review compares the pharmacology of and clinical trial results of subdermal implants versus IUSs to help clinicians make a rational decision about which one is likely to be preferable and under which circumstances. It is not meant to override user choice which is always worthy of serious consideration even if it appears to the provider to be inappropriate. Pharmacology of subdermal implants and intrauterine systems Pharmacokinetics There are currently three different types of levonorgestrel(LNG) releasing intrauterine systems(LNG- OBSTETRICS & GYNAECOLOGY FORUM 2019 | ISSUE 1 | 4