A risk-benefit assessment of the levonorgestrel-releasing intrauterine system.

The levonorgestrel-releasing intrauterine system (LNG-IUS), has been developed by Leiras Pharmaceuticals, Turku, Finland. It is a new systemic hormonal contraceptive that releases levonorgestrel 20 micrograms every 24 hours. The device provides fertility control comparable with that of female sterilisation, complete reversibility and convenience, and has an excellent tolerability record. The low dosage of levonorgestrel released by its unique delivery system ensures minimal hormone-related systemic adverse effects, which tend to be in the category of 'nuisance' rather than hazardous, and gradually diminish after the first few months of use. In some respects, the contraceptive characteristics of the LNG-IUS have over-shadowed a substantial range of noncontraceptive beneficial effects that are rarely seen with inert or copper-releasing intrauterine contraceptive devices (IUDs), and have important and positive gynaecological and public health implications. This applies particularly to the profound reduction in duration and quantity of menstrual bleeding, and alleviation of dysmenorrhoea, which are associated with the use of the device. Recent studies have shown that the LNG-IUS is effective in preventing endometrial proliferation associated with oral or transdermal estradiol therapy, and in inducing regression of endometrial hyperplasia. Further research is required to determine whether it has a role in regulating the growth of uterine fibroids, and preventing pelvic inflammatory disease. The unique unwanted noncontraceptive effects of the system, including possible development of functional ovarian cysts, and the relationship between menstrual bleeding pattern and ovarian function, also require better understanding, in order to offer appropriate patient counselling and maximise acceptability and continuation of use of the method.

PIP: The levonorgestrel-releasing intrauterine system (LNG-IUS) provides fertility control comparable to female sterilization, convenience, and complete reversibility. This method appears to combine the benefits of oral contraception and the IUD, while avoiding most of their side effects. The low level of LNG released (20 mcg every 24 hours) minimizes the systemic adverse effects associated with hormonal contraception. Unlike inert or copper IUDs, the LNG-IUS is associated with a profound reduction in the duration and quantity of menstrual bleeding and alleviates dysmenorrhea. Moreover, there is evidence that the LNG-IUS prevents the endometrial proliferation associated with estradiol therapy and induces regression of endometrial hyperplasia; its potential for regulating the growth of uterine fibroids and preventing pelvic inflammatory disease remains undetermined. Although large multicenter studies have not detected differences in cervical cytology or breast cancer incidence between copper IUD and LNG-IUS users, long-term epidemiological studies are needed to confirm this finding. Fundal positioning of the LNG-IUS is essential to ensure uniform exposure of the endometrium to the progestogen, prevent expulsion, and maximize efficacy. A promising future use for the LNG-IUS is in protecting the endometrium during postmenopausal hormone replacement therapy. Overall, the research suggests that the LNG-IUS comes close to meeting many of the requirements of an ideal contraceptive.

Selecting patients and inserting the Progestasert.

PIP: In this article, the author discusses what is presently known about the Progestasert IUD, a progesterone delivery system. Progestasert delivers progesterone on a daily basis and in continuous fashion into the endometric cavity. It has no systemic effects, although there is increasing evidence of its effects on hypermenorrhea na dysmenorrhea. Evidence suggests that Progestasert may avoid one of the major problems associated with former IUDs (particularly the Dalkon Shield): salpingitis. More than 10 years ago, physicians observed during sterilization procedures that a large number of women wearing inert or copper IUDs had salpingitis. Data from 27 Progestasert users show that none had salpingitis at the time of sterilization. Progestasert may also carry a lower risk of pelvic inflammatory disease associated with IUD use. A study in Helsinki found only 3 cases of pelvic inflammatory disease in 20,000 women years use of progestin (Levonorgestrel) impregnated IUDs, compared to the expected incidence (according to the Center for Disease Control) of 1/100 woman years. Additionally, in a study involving over 300 patients, the use of prophylactic antibiotics after insertion twice a day for 5 days and inserting Progestasert during the time ovulation rather at the time of menstruation produced no cases of the pelvic inflammatory conditions usually associated with the insertion procedure. Concerning the risks of ectopic pregnancy, evidence suggests that progestasert tends towards more ectopics when compared to the copper IUDs, but towards less when compared to not using any contraception. Although Progestasert is not contraindicated in nulliparous patients, caution should be taken with such patients.^ieng

[Steroid intra-uterine contraception: progesterone-releasing devices. II. Insertion, clinical problems and contraceptive dependability]. / Contraccezione intrauterina steroidea. Dispotivi liberanti progesterone. II. Inserzione, problemi clinici e sicurezza contraccettiva.

PIP: The advantages and disadvantages of the progesterone-releasing intrauterine device (IUD), Progestasert, are investigated, relying on the published literature and the authors' own experiences. Insertion of the Progestasert presents very few problems except in certain cases, particularly in nulliparous women. A complete gynecologic examination is indispensible before insertion to guarantee the absence of contraindications (e.g., pregnancy, anatomically abnormal uterus, tumors, pelvic inflammatory disease, acute cervicitis). Pain or discomfort at insertion appears infrequently, except among nulliparas. Similarly, pain after insertion is rare, but occurs most often in nulliparous women. Because of the insertion technique required for this IUD, cases of perforation of he uterus or cervix are virtually nonexistent. Expulsion of the Progestasert is very infrequent; it appears that incorrect insertion is the primary cause of expulsion. All studies verify a decrease in the expulsion rate after the 1st month of use. The incidence of pelvic inflammatory disease in Progestasert users is significantly lower than in users of other IUDs. This may be due, in part, to the shape of the device, which does not have wide surface areas and has no sharp or pointed edges which can become embedded in the endometrial wall. Additionally, the nature of the insertion device, guaranteeing lack of contact between the transverse arm of the IUD and the vagina, assures the sterility of the IUD even at the moment of introduction into the uterus, limiting the transport of bacteria into the cavity. Lack of sufficient data on ectopic pregnancies in Progestasert users impedes a complete evaluation and definition of the problem with this particular device. One of the most frequent reasons for discontinuing use of the IUD is distrubance of the menstrual cycle. Increase in menstrual blood loss, prolongation of the menstrual period, and intermenstrual bleeding are disturbances found in users of most IUDs. The Progestasert, however, appears to decrease menstrual bleeding and shorten the menstrual period in all cases. The advantages of the Progestasert are indisputable in treating dysmennorhea. All studies agree on the attributes of topical release of progesterone in treating this illness. Studies report disappearance of symptoms in 35% of dysmennorheic patients and a marked reduction of symptoms in 65%. Not enough data exist to draw any conclusions about the teratogenic action of the Progestasert. In normal pregnancies, however, natural progesterone is found in much higher levels than that released by the IUD. Theoretically, the hormone released by the IUD should not interfere with normal fetal development. The failure rate of Progestasert is equal to or lower than that of other IUDs. Overall, the Progestasert represents a remarkable improvement over conventional IUDs.^ieng

Transdermal estrogen with a levonorgestrel-releasing intrauterine device for climacteric complaints: clinical and endometrial responses.

OBJECTIVE: Our purpose was to study the effects of intrauterine release of a daily dose of 20 micrograms levonorgestrel by an intrauterine device on climacteric symptoms, bleeding pattern, and endometrial histologic features in postmenopausal women receiving transdermal estrogen replacement therapy. STUDY DESIGN: Forty parous postmenopausal women were randomly allocated into two groups for 1 year: 20 women receiving a continuous transdermal daily dose of 50 micrograms of estradiol had a levonorgestrel-releasing intrauterine contraceptive device inserted, and the control group of 20 women received a continuous oral dose of 2 mg of estradiol valerate and 1 mg of norethisterone acetate daily. The climacteric symptoms, bleeding patterns, endometrial thickness, and endometrial changes in biopsy samples were analyzed. Serum levels of estradiol in both groups and levonorgestrel levels in the intrauterine device group were also determined. RESULTS: Both treatment regimens effectively relieved climacteric symptoms. Spotting was more common in the intrauterine contraceptive device group than in the oral therapy group for the first 3 months. After that, the proportion of women without any bleeding was similar in both groups. Two patients in each group dropped out because of bleeding. CONCLUSION: These preliminary findings suggest that the levonorgestrel-releasing intrauterine contraceptive device is a useful alternative mode of progestin administration for certain selected women receiving estrogen replacement therapy.

PIP: The purpose was to study the effects of intrauterine release of a daily dose of 20 mcg levonorgestrel by an IUD on climacteric symptoms, bleeding pattern, and endometrial histologic features in postmenopausal women receiving transdermal estrogen replacement therapy. 40 parous postmenopausal women were randomly allocated into 2 groups for 1 year. They were required to be parous, to have an intact uterus, and to have had amenorrhea for at least 6 months but less than 5 years. 20 women received a combination of 50 mcg of estradiol per 24 hours delivered transdermally from a patch, and received estrogen pretreatment for 1 month to make insertion of a levonorgestrel-releasing IUD (Levonova), which was installed a month later, easier. This combination was continued for 1 year. The control group of 20 women received an established form of continuous oral estrogen and progestin with a daily dose of 2 mg of estradiol, and 1 mg of norethindrone acetate also administered for 1 year. Checkup visits were scheduled at 3, 6, and 12 months. The climacteric symptoms, bleeding patterns, endometrial thickness, and endometrial changes in biopsy samples were analyzed. The increase in estradiol concentration was similar in both groups, and the mean concentrations of levonorgestrel in the IUD group were 216 +or- 25 pg/ml at 3 months, 209 +or- 11 pg/ml at 6 months, and 212 + 10.5 pg/ml at 12 months. Both treatment regimens effectively relieved climacteric symptoms. The IUD group experienced more days of bleeding, primarily spotting, during the first 3 months than did the oral therapy group but the differences between the groups had disappeared by 6 months. Both treatments resulted in an atrophic endometrium developing from a proliferative one. Two patients in each group dropped out because of bleeding. The levonorgestrel-releasing IUD is a useful alternative mode of progestin administration for certain selected women receiving estrogen replacement therapy.

The levonorgestrel-releasing intrauterine device: a wider role than contraception.

The Levonorgestrel-releasing intrauterine device (LNG IUD) provides excellent contraception; it may reduce the rate of pelvic inflammatory disease (PID) and ectopic pregnancy compared to other 'modern' copper releasing IUDs; it can safely be used in the puerperium for breast-feeding mothers, and it significantly reduces menstrual blood loss and pain. While it was developed primarily as a contraceptive, its potential role in managing heavy and painful menstruation and the symptoms of the climacteric may eventually be just as important. Amongst developed countries New Zealand and Australia have some of the highest hysterectomy rates. By the age of 50 years 1 in 4 women in New Zealand and 1 in 5 women in Australia will have had a hysterectomy (A,B). In New Zealand 90% of these are performed for heavy menstrual bleeding and fibroids (A). The LNG IUD has been shown to be effective treatment for both these conditions and its introduction to New Zealand and Australia would offer women an additional choice beyond surgery.