The incidence of actinomyces-like organisms in Papanicolaou-stained smears of copper- and levonorgestrel-releasing intrauterine devices.

Actinomyces-like organisms (ALOs) are a common finding in Papanicolaou-stained cervico-vaginal smears (PAP smears) of women using an intrauterine device (IUD). The incidence of ALOs positive PAP smears depends on the type of IUD. Pelvic actinomycosis is a severe disease that may require hysterectomy and salpingo-oophorectomy. In a retrospective study we compared the incidence of ALOs positive PAP smears in users of the new levonorgestrel-releasing intrauterine device (LNG-IUD) (n = 52) with the incidence in Multiload Copper IUD (ML375) users (n = 104). All IUDs had been inserted from 1996-1998. Women with a follow-up period of more than 9 months were included into the final analysis (LNG-IUD: n = 34; ML375: n = 65). The incidence of ALOs in LNG-IUD users (2.9%) was significantly lower than in ML375 users (20%). Clinical consequences of ALOs positive PAP smears are discussed controversially. The low incidence in the LNG-IUD users probably leads to less IUD-removals, reinsertions and less pelvic-inflammatory-diseases.

Amenorrhoea despite displaced levonorgestrel intra-uterine system.

PIP: A 29-year-old woman presented to the gynecology outpatient clinic with abdominal discomfort following the insertion of a levonorgestrel intrauterine system (LNG-IUS). It was noted that although the patient remained amenorrheic since the insertion, there was a persistent left iliac fossa discomfort, which was constant in nature and not made worse by intercourse. On examination, there was a vague tenderness in the left iliac fossa, and a transvaginal ultrasound scan showed bright echoes outside the uterus suggestive of an extrauterine IUS. Thus, arrangements were made for an admission for hysteroscopy and laparoscopy, proceeding to laparotomy if required. Following the procedures, the patient reported disappearance of the discomfort, although the LNG-IUS had not yet been retrieved. X-ray revealed the device lying high in the abdomen and laparoscopy was conducted. The LNG-IUS itself was buried, but was easily retrieved with gentle counteraction on the omentum through a 5 mm laparoscopy portal. Overall, this case emphasizes the importance of an X-ray as well as an ultrasound investigation in such cases.^ieng

Mirena intrauterine system seeks U.S. nod.

PIP: Mirena, the levonorgestrel intrauterine system, is seeking approval from the US Food and Drug Administration, with Berlex Laboratories filing a new drug application with the agency. National family planning experts have been calling for US introduction of this unique intrauterine contraceptive that delivers a 20 mcg daily dose of locally acting hormone directly in the uterus since 1990. Several health experts indicated that Mirena would provide American women with the convenience and high contraceptive efficacy characteristics of IUDs while reducing menstrual flow and cramps. However, since Mirena has a different insertion procedure from previous devices, it will require hands-on instruction. In view of this, a proprietary device is developed which should aid in inserting the IUD. Appropriate physician education and patient support programs will accompany the product upon approval.^ieng

Effect of the levonorgestrel-releasing intrauterine system on uterine myomas in a renal transplant patient.

The levonorgestrel-releasing intrauterine system (LNG-IUS) has been used in the treatment of both idiopathic menorrhagia and adenomyosis. An electronic search of the on-line medical literature revealed no reports of its use for menorrhagia secondary to uterine myomas. Presented here is the successful treatment of uterine myomas with menorrhagia in a woman with a renal transplant. There was a significant reduction in menorrhagia, dysmenorrhea, and uterine and myoma size with the use of the LNG-IUS. We believe that this system provides an alternative to conventional hysterectomy and gonadotrophin-releasing hormonal analog medical treatment for uterine myomas, with a possibly inhibitory effect on myoma growth.

PIP: This case report focuses on the effect of the levonorgestrel-releasing intrauterine system (LNG-IUS) on uterine myomas in a renal transplant patient. The successful treatment of uterine myomas with menorrhagia in a 43-year-old woman with a renal transplant is presented. Preinsertion, the uterine cavity was not distorted and it measured 12 cm. The LNG-IUS was inserted without difficulty. On follow-up, 3 months later, improvement was observed. Her cycles were regular with heavy flow only on the first 2 days. The uterus was 10 weeks¿ size on pelvic examination and her hemoglobin was 9.5 g/dl. One year after the initial insertion, she was asymptomatic with normal menstrual flow. The uterus was 6-8 weeks' size on pelvic examination and the uterine cavity was 6 cm. The largest intramural fibroid measured 10-15 mm. Hemoglobin was 10.8 g/dl without any hematinics. There was a significant reduction in menorrhagia, dysmenorrhea, and uterine and myoma size with the use of the LNG-IUS. Thus, the system provides an alternative to conventional hysterectomy and gonadotrophin-releasing hormonal analog medical treatment for uterine myomas, with a possibly inhibitory effect on myoma growth.

Interleukin-6 and tumor necrosis factor-alpha concentrations in the intrauterine cavity of postmenopausal women using an intrauterine delivery system releasing progesterone. A possible mechanism of action of the intrauterine device.

Intrauterine devices (IUD) provide effective contraception. The current study evaluates the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in the intrauterine fluid of postmenopausal women using an intrauterine delivery system releasing progesterone (IDS-P). Intrauterine fluid was obtained by lavage, and IL-6 and TNF-alpha were analyzed using an enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed with a one-way analysis of variance (ANOVA). Intrauterine fluid IL-6 levels were 33.6 vs 6.09 pg/sample IDS-P vs no IDS-P (p = 0.0301). Intrauterine TNF-alpha levels for women using the IDS-P were higher than in nonusers, but the differences did not reach statistical significance. IL-6 and TNF-alpha levels were increased in the intrauterine cavity of postmenopausal women with an IDS-P. These data suggest that secreted cytokines could be a potential mechanism of IUD contraceptive efficacy.

PIP: This paper examines the possible mechanism of action of a progesterone-releasing IUD (P-IUD) by evaluating the concentration of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in the intrauterine fluid of postmenopausal women using such a device. IL-6 and TNF-alpha were examined using an enzyme-linked immunosorbent assay (ELISA), while the intrauterine fluid was obtained by lavage. Intrauterine fluid IL-6 levels were 33.6 vs. 6.09 pg/sample for P-IUD vs. non-P-IUD users (p = 0.0301). Higher intrauterine TNF-alpha levels were observed in women using the P-IUD than in nonusers. The cells found in the intrauterine fluid of the P-IUD users were mostly histiocytes (macrophages) based on their morphologic characteristics. Increased IL-6 and TNF-alpha levels were found in the intrauterine cavity of postmenopausal women using a P-IUD. These results indicate that cytokines could play a significant role in the contraceptive mechanism of action of the IUD when used by premenopausal women.

Successful use of levonorgestrel intrauterine system in a HIV positive woman.

After trying other contraceptive methods a woman with HIV disease found use of the levonorgestrel intrauterine system (IUS) very satisfactory, and benefited from the amenorrhoea it induced. She continued to use condoms. Other advantages of using the IUS were freedom from regular clinic visits, no need for daily pill taking, and absence of drug interactions.

PIP: The case presented in this paper suggests that the levonorgestrel intrauterine system may be an excellent contraceptive method for HIV-positive women. At presentation to a UK family planning clinic, a 32-year-old nulliparous woman was using Depo-Provera for contraception; however, she was bleeding irregularly and complained of acne and lack of vaginal lubrication. The Mirena intrauterine system was considered because it offered lighter menstrual periods or amenorrhea, no need for regular clinic visits, reliable contraception, and fewer systemic side effects than other progestogen-only methods. At follow-up 6 weeks after Mirena insertion, the woman reported one light period, pain on the day of fitting only, and no progestogenic side effects. The reduced blood loss associated with this method is beneficial if mild anemia is present and may reduce exposure of an HIV-negative male partner to infected blood. Moreover, the system's effectiveness is not compromised by the broad-spectrum antibiotics or liver enzyme-inducing drugs taken by women with HIV/AIDS.

Intrauterine devices. The optimal long-term contraceptive method?

OBJECTIVE: To review selected data on the effectiveness, safety, cost and technical ease of intrauterine device (IUD) use compared with Norplant and surgical sterilization. STUDY DESIGN: Literature review. RESULTS: IUDs are highly effective, safe and relatively inexpensive methods of contraception that may offer advantages for some women over other long-term methods, such as sterilization and Norplant. IUDs provide protection against pregnancy comparable to that provided by female sterilization, and they may be more effective than Norplant. IUDs have a long duration of effectiveness: the copper T 380A (TCu380A) is effective for at least 10 years, and the levonorgestrel (LNg) IUD appears to be effective for at least 7. Norplant is effective for only five years. Both types of IUD can disrupt menstrual bleeding patterns, although the patterns of bleeding are different. Copper IUDs often increase blood loss, whereas the LNg IUD, like Norplant, substantially reduces menstrual bleeding. The most important adverse outcome associated with IUD use is higher rates of pelvic inflammatory disease; careful attention to proper insertion techniques can reduce this risk substantially, and LNg IUDs may cause no increase in risk. IUDs, like both sterilization and Norplant, provide no protection against sexually transmitted disease. The TCu380A IUD is extremely cost-effective. There is as yet no public sector price for the LNg IUD, which has not been approved by the U.S. Food and Drug Administration and is not provided by family planning donor organizations. If it can be made available to the public sector at a price substantially less than its present market price, the LNg IUD would be a useful addition to the contraceptive armamentarium for developing countries. CONCLUSION: Providers, consumers and family planning program managers should begin to see IUDs as potential substitutes for both surgical sterilization and Norplant.

PIP: This study reviews literatures on the effectiveness, safety, cost and technical ease of IUD use as compared with Norplant and surgical sterilization. Findings revealed that IUDs are highly effective, safe and relatively inexpensive methods of contraception that may offer advantages for some women over other long-term methods, such as sterilization and Norplant. IUDs provide protection against pregnancy comparable to that provided by female sterilization, and they may be more effective than Norplant. IUDs have a long duration of effectiveness: the copper T 380A is effective for at least 10 years, and the levonorgestrel (LNG) IUD seems to be effective for at least 7 years. Norplant is effective for only 5 years. Both types of IUD can disturb menstrual bleeding patterns, although the patterns of bleeding are different. Copper IUDs often increase blood loss, whereas the LNG IUD, like Norplant, substantially reduces menstrual bleeding. The most important adverse outcome associated with IUD use is higher rates of pelvic inflammatory disease; careful attention to proper insertion techniques can reduce this risk substantially, and LNG IUDs may cause no increase in risk. IUDs, like both sterilization and Norplant, provide no protection against sexually transmitted diseases.

Medical treatment of a grossly enlarged adenomyotic uterus with the levonorgestrel-releasing intrauterine system.

Adenomyosis is an important cause of menorrhagia. Besides hysterectomy, the treatment options for adenomyosis have been limited. Presented here is the successful treatment of adenomyosis in a woman presenting with menorrhagia, dysmenorrhea, and an enlarging uterus, for whom conservative therapy initiated with mefenamic acid was unsatisfactory. The patient had insertion of the levonorgestrel-releasing intrauterine system (LNG-IUS). A marked decrease in uterine size occurred within 12 months of insertion accompanied by resolution of the menorrhagia and dysmenorrhea. Thus, the LNG-IUS is a viable option and represents a real advance in the treatment of adenomyosis.

PIP: Adenomyosis is the major cause of menorrhagia, dysmenorrhea, and an enlarged uterus, which causes great distress to the patient. Surgical hysterectomy has been used in the past as a treatment option for adenomyosis, but acceptability of this intervention is minimal due to an increased risk in morbidity and mortality. This article presents the successful medical treatment of an enlarged adenomyotic uterus with the levonorgestrel-releasing intrauterine system (LNG-IUS) using a case report of a 42-year-old woman with adenomyosis who received the LNG-IUS as a long-term therapy for menorrhagia and dysmenorrhea. Regular menstruation without pain was reported after 3 months of treatment with a 27% decrease in uterine size after 9 months. The effectiveness of the LNG-IUS was hypothesized to be due to two factors: 1) decidualization and subsequent marked atrophy of the endometrium; 2) direct action of the hormone on the foci of the adenomyosis. A reported side effect of the LNG-IUS is the irregularity of bleeding during the initial treatment. The study suggests that use of the LNG-IUS is a viable option and could greatly advance the treatment of adenomyosis.

Lipid effects of an intrauterine levonorgestrel device or oral vs. vaginal natural progesterone in post-menopausal women treated with percutaneous estradiol.

BACKGROUND: The ideal progestin for combined hormone replacement therapy should be free of adverse effects on lipid metabolism. We therefore examined lipid profiles during continuous hormone replacement therapy (HRT) with an estradiol-gel combined with either a levonorgestrel-releasing intrauterine device (LNG-IUD) or oral/vaginal natural progesterone. METHODS: Sixty menopausal women recruited in this open, non-randomised parallel three-group study received percutaneous gel containing 1.5 mg of estradiol daily. Progestin was administered to the women with an LNG-IUD (n = 20), as oral natural progesterone (n = 21) 100 mg daily on the 1-25 calendar days of the month or as vaginal progesterone (n = 19) 100-200 mg daily on the 1-25 calendar days of the month. Serum concentrations for total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and sex hormone binding globulin (SHBG) were measured at 0, 6 and 12 months. The median (and 95% confidence interval) of the serum SHBG, total, LDL-, HDL- cholesterol and triglycerides concentrations at baseline and after 6 and 12 months of the study and the ratio of 6 and 12 months values to baseline values were calculated. RESULTS: Total cholesterol was significantly decreased (8%) in the vaginal progesterone group at the end of the trial. HDL-cholesterol did not change in either of the progesterone groups, while a slight but transient decrease (median 15%) was seen at 6 months in the LNG-IUD group. There were no significant changes in triglycerides or LDL-cholesterol concentrations in any group. SHBG did not change significantly in the LNG-IUD and vaginal progesterone groups, while a slight but transient increase was seen in oral P group at 6 months. CONCLUSIONS: As the only significant harmful effect observed was a transient decrease in HDL-cholesterol in the LNG-IUD group at 6 months, each of these HRT-administration methods can be regarded as being safe in their effects on lipid metabolism.

PIP: This study examined the lipid profiles during continuous hormone replacement therapy (HRT) with an estradiol gel combined with either the levonorgestrel-releasing IUD (LNG-IUD) or oral/vaginal natural progesterone. In an open and nonrandomized parallel three-group study conducted in Finland, 60 menopausal women were administered a percutaneous gel containing 1.5 mg of estradiol daily. Progestin was administered to 20 women with an LNG-IUD, as oral natural progesterone (100 mg daily) to 21 women on calendar days 1-25, or as vaginal progesterone (100-200 mg daily) to 19 women on calendar days 1-25. Serum concentrations of total cholesterol, low-density lipoprotein (LDL)-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglycerides, and sex hormone binding globulin (SHBG) were measured at 0, 6, and 12 months. Results revealed an 8% decrease of total cholesterol in the vaginal progesterone group. HDL-cholesterol remained stable in both progesterone groups, with a 15% decrease at 6 months in the LNG-IUD group. Triglycerides and LDL-cholesterol concentrations were found to have insignificant changes. SHBG was observed to be stable in the LNG-IUD and vaginal progesterone groups, with a slight increase seen in the oral progesterone group after 6 months. This study confirms the safety of this type of HRT with regard to lipid metabolism, except for the transient decrease in HDL-cholesterol among LNG-IUD users at 6 months.

Endometrial morphology during hormone replacement therapy with estradiol gel combined to levonorgestrel-releasing intrauterine device or natural progesterone.

OBJECTIVES: To evaluate endometrial responses to three different forms of amenorrhea-inducing HRT in postmenopausal women. MATERIAL AND METHODS: Fifty-one postmenopausal women completing a one-year HRT trial with percutaneous estradiol gel containing 1.5 mg estradiol daily combined with a levonorgestrel-releasing intrauterine device (LNG-IUD) (n=18), or natural progesterone 100 mg daily orally (n= 19) or vaginally (n=15) during 1-25 calendar days of each month. Endometrial thickness and uterine size were measured by transvaginal ultrasound, and endometrial cytology/histology was assessed from specimens taken by needle aspiration before the study and at 12 months. RESULTS: Before medication, the median endometrial thickness was 2.0 mm in the LNG-IUD group, 2.4 mm in the oral P group and 2.5 mm in the vaginal P group. At 12 months of therapy the respective values, 3.0, 2.7 and 2.4 mm, did not differ significantly from the initial values. LNG-IUD induced epithelial atrophy in all women, which was accompanied by stromal decidualization in 12 women. On the contrary, only four women in the oral P group and five women in the vaginal P group had an inactive or atrophic endometrium. The remaining cases were dominated by proliferative features. No hyperplasia was seen in any of the groups. CONCLUSION: LNG-IUD appeared to be an effective method of counteracting the stimulatory effect of estrogen on the endometrium, whereas natural progesterone given orally or vaginally was not sufficiently effective in this function at the doses used. The vaginal and oral administrations of progesterone did not differ from each other in this respect.

PIP: This study evaluated the endometrial morphological response to the levonorgestrel-releasing IUD (LNG-IUD) and to natural progesterone administered orally or vaginally in postmenopausal women using percutaneous estradiol gel on a daily basis. The study employed 51 postmenopausal women who completed a 1-year hormone replacement therapy trial of 1.5 mg estradiol daily combined with a LNG-IUD (n = 18), 100 mg oral progesterone (n = 19), or 100 mg vaginal progesterone (n = 15) during 1-2 calendar days of each month. Using a transvaginal ultrasound, endometrial thickness was measured prior to and 12 months after the study. Prior to the study, endometrial thickness was 2.0, 2.4, and 2.5 mm for the LNG-IUD, oral progesterone, and vaginal progesterone groups, respectively. During the transvaginal ultrasound (after 12 months) the respective values were 3.0, 2.7, and 2.4 mm, respectively, which was considered normal among postmenopausal women. 12 of the women who were administered the LNG-IUD were found to have epithelial atrophy accompanied by stromal decidualization. On the other hand, 4 women in the oral progesterone and 14 in the vaginal progesterone groups were found to have inactive or atrophic endometrium. Proliferative features dominated the remaining cases, while hyperplasia was not observed in any of the cases. This study confirms the efficacy of the LNG-IUD in suppressing the stimulatory effect of estrogen on the endometrium, while oral and vaginal progesterone were not sufficiently effective at the doses used.

Auditing the introduction of a new product to a family planning service.

The audit aimed to develop a questionnaire to monitor how a new method od contraception is offered in service by identifying local demand and assessing levels of awareness of and interest in a new product (Mirena(R)) The audit also aimed to establish those suitable for Mirena and the numbers of Mirena fitted and characteristics of recipients.

PIP: The National Coordinating Unit for Clinical Audit in Family Planning relies on pilot sites throughout the UK to develop informational materials about new products. Described in this paper is an audit conducted in Chesterfield Community Services (North Derbyshire Community Health Trust) in 1996 with the aim of developing a questionnaire for identifying local awareness of and demand for the Mirena IUD. Family planning staff completed questionnaires for 57 new patients or women requesting a change in contraceptive method. Of the 49 women who identified their current method of contraception, 29 were using condoms, 14 were on the pill, and 2 were IUD users. 41 consultations (72%) included a discussion of Mirena; in the remaining 16 cases, the women had decided on a method prior to consultation. 21 women had heard of the Mirena IUD before their visit to the clinic and 18 expressed an interest in it. Only 7 women actually obtained a Mirena IUD; in 1 other case, the device was not available at the clinic. Another 7 women opted for a copper IUD. The mean age of Mirena acceptors (32.9 years) was significantly higher than the mean age of the sample (28.2 years). Of concern is the possibility that women who want Mirena will be directed toward less expensive IUDs in greater supply in UK clinics. It is recommended that a protocol be established for cases in which Mirena is preferred and suitable, but no supply is available.

Randomised comparative trial of the levonorgestrel intrauterine system and norethisterone for treatment of idiopathic menorrhagia.

OBJECTIVE: To compare the efficacy and acceptability of the levonorgestrel intrauterine system and norethisterone for the treatment of idiopathic menorrhagia. DESIGN: A randomised comparative parallel group study. SETTING: Gynaecology outpatient clinic in a teaching hospital. PARTICIPANTS: Forty-four women with heavy regular periods and a measured menstrual blood loss exceeding 80 ml. METHODS: Twenty-two women had a levonorgestrel intrauterine system inserted within the first seven days of menses, and 22 women received norethisterone (5 mg three times daily) from day 5 to day 26 of the cycle for three cycles. MAIN OUTCOME MEASURES: The main outcome measure was the change in objectively assessed menstrual blood loss after three months of treatment. RESULTS: When menstrual blood loss at three months was expressed as a percentage of the control, the levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median reduction 103 ml; range 70 to 733 ml), and oral norethisterone by 87% (median reduction 95 ml; range 56 to 212 ml). After three cycles of treatment 76% of the women in the levonorgestrel intrauterine system group wished to continue with the treatment, compared with only 22% of the norethisterone group. CONCLUSIONS: Both the levonorgestrel intrauterine system and oral norethisterone in this regimen provided an effective treatment for menorrhagia in terms of reducing menstrual blood loss to within normal limits. The levonorgestrel intrauterine system was associated with higher rates of satisfaction and continuation with treatment, and thus offers an effective alternative to currently available medical and surgical treatments for menorrhagia.

PIP: The efficacy and acceptability of two new approaches to the treatment of idiopathic menorrhagia--the levonorgestrel intrauterine system and norethisterone--were compared in 45 women recruited from a gynecology outpatient clinic at a UK teaching hospital. All study participants had heavy regular periods and a measured menstrual blood loss exceeding 80 ml. 22 women were randomly assigned to have a levonorgestrel intrauterine system inserted within the first 7 days of menses and 22 women received 5 mg of norethisterone 3 times daily from day 5 to day 26 of their cycle for 3 cycles. Compared to baseline, the levonorgestrel intrauterine system reduced menstrual blood loss by 94% (median reduction, 103 ml) and oral norethisterone reduced it by 87% (median reduction, 95 ml). Recorded in both treatment groups were significant decreases in breast tenderness, mood swings, intermenstrual bleeding, and interferences in daily life caused by menstruation. After 3 treatment cycles, 64% of women in the levonorgestrel group indicated they liked the treatment "well" or "very well" and 77% elected to continue the regimen. In the norethisterone group, these rates were only 44% and 22%, respectively. Although both regimens reduced menstrual blood loss to within normal limits, the levonorgestrel intrauterine system was associated with higher satisfaction and thus offers an effective alternative to currently available medical and surgical treatments for menorrhagia.

Progestin receptor isoforms and prostaglandin dehydrogenase in the endometrium of women using a levonorgestrel-releasing intrauterine system.

This study has examined endometrial tissue in 14 normal women prior to insertion of a levonorgestrel-releasing intrauterine system (LNG-IUS) and thereafter longitudinally for up to 12 months post-insertion. The specific endpoints examined by immunohistochemistry were progesterone receptor (PR) subtypes A + B, oestrogen receptor (ER) and prostaglandin dehydrogenase (PGDH). Two antiprogesterone receptor antibodies, one specific to PR(B) subtype and the other to PR subtype A + B, were employed to examine the localization of both PR isoforms. The activity of PGDH, a progesterone dependent enzyme, was also measured. ER and PR(A+B) and PR subtype B were significantly down-regulated in glands and stroma in the presence of continuous intrauterine LNG delivery. There was an apparent increase in PR(A) immunoreactivity in endometrial glands between 6 and 12 months post-insertion. Consistent with down-regulation of both isoforms of PR was reduced glandular PGDH immunostaining following LNG-IUS insertion, and PGDH activity (as measured by metabolism of excess substrate in vitro). Furthermore, PGDH activity, known to be localized in the glands, significantly increased (P < 0.05) at 12 months post-insertion, coinciding with the observed increase in glandular PR(A+B) immunoreactivity at this time. Since the LNG-IUS suppresses the PR(B) so strongly, PR(A) is likely to be the subtype that mediates long term LNG action in the endometrium. PR(B) is the more suppressed of the two subtypes, and only PR(A) rises along with PGDH activity. Alterations to normal endometrial morphology and function, e.g. perturbation of normal sex steroid receptor expression, following exposure to high concentrations of local LNG, may play a role in the aetiology of bleeding disorders associated with the LNG-IUS. Further elucidation of local uterine mediators involved in the mechanism of bleeding problems is required.

PIP: The effects of a levonorgestrel-releasing intrauterine system (LNG-IUS) on endometrial tissue were investigated in 14 UK women who were followed for 12 months after its insertion. Of particular interest was the etiology of menstrual aberration associated with progestogen-only contraception. In the presence of continuous intrauterine LNG delivery, estrogen receptor and progesterone receptor (PR) subtype A + B and subtype B were significantly downregulated in the endometrial glands and stroma. There was no apparent increase in PR subtype A immunoreactivity in endometrial glands 6-12 months after LNG-IUS insertion. Also observed was reduced glandular prostaglandin dehydrogenase (PGDH) staining and activity. PGDH activity significantly increased at 12 months post-insertion coinciding with the increase in glandular PR subtype A + B. Since the LNG-IUS suppresses the PR subtype B so strongly and only PR subtype A rises along with PGDH activity, PR A is likely the subtype that mediates long-term LNG action in the endometrium. Perturbation of normal sex steroid receptor expression after exposure to high concentrations of local LNG may play a role in the bleeding disorders associated with use of the LNG-IUS. Examination of more local mechanisms in endometrium exposed to an LNG-IUS should help elucidate some of the potential mechanisms regulating endometrial bleeding.

Morphological and functional features of endometrial decidualization following long-term intrauterine levonorgestrel delivery.

Irregular bleeding remains a common reason for the discontinuation of progestin-only contraception. The levonorgestrel releasing intrauterine system (LNG-IUS) has profound morphological effects upon the endometrium. Specific features are gland atrophy and extensive decidual transformation of the stroma. Morphological changes in the endometrium may be associated with perturbation of mechanisms regulating normal endometrial function. This study describes endometrial stromal and glandular features prior to and up to 12 months following insertion of the LNG-IUS. Comparison is made with first trimester decidua. In order to elucidate further mechanisms governing endometrial function with local intrauterine delivery of LNG, we here report histological features consistent with decidualization; a significant increase in granulocyte-macrophage colony stimulating factor (GM-CSF) immunoreactivity in decidualized stromal cells; glandular and stromal prolactin receptor expression and an infiltrate of CD56 + large granular lymphocytes and CD68 + macrophages. We are unaware of previous reports which have documented longitudinally both morphological and functional observations in endometrium exposed to local intrauterine levonorgestrel delivery. These studies demonstrate that long-term administration of intrauterine levonorgestrel results in features of altered morphology and function. No correlation was apparent between the end points in the study and the bleeding patterns described by the subjects. Further evaluation of these features in the context of menstrual bleeding experience may contribute to a better understanding of this troublesome side-effect which often leads to dissatisfaction and discontinuation of the intrauterine system.

PIP: The levonorgestrel-releasing intrauterine system (LNG-IUS) has profound morphologic effects on the endometrium, including gland atrophy and extensive decidual transformation of the stroma. The present study investigated these morphologic changes in tissue samples collected from 14 UK women up to 12 months after insertion of the LNG-IUS. Observed histologic features consistent with decidualization included a significant increase in granulocyte-macrophage colony stimulating factor immunoreactivity in decidualized stromal cells, glandular and stromal prolactin receptor expression, and an infiltrate of CD56+ large granular lymphocytes and CD68+ macrophages. The features of pseudo-decidualization closely resembled the morphology of early pregnancy decidua. These findings confirm that the stromal compartment of the endometrium undergoes changes consistent with decidualization for at least up to 12 months after insertion of an LNG-IUS. There was no correlation between the study endpoints and the menstrual patterns reported by study subjects. Further study of the decidualized nature of the stromal cells in the LNG-exposed endometrium should enhance understanding of the mechanisms responsible for breakthrough bleeding in users of progestogen-only contraceptives.

Internet opens access to contraceptive methods.

PIP: US women are able to import contraceptive agents not available in the US from two Canadian companies who advertise their products on the World Wide Web. US regulations permit importation of small quantities of drugs for personal use even if the drugs have not received US Food and Drug Administration (FDA) approval. Most US women order the Protectaid contraceptive sponge, which is sold over-the-counter in Canada, because contraceptive sponges are no longer available in the US. One of the companies also exports the levonorgestrel-releasing IUD, but, in this case, the company only ships the product to physicians. The legal liabilities of inserting an IUD that has not received FDA approval are the same as for any sanctioned product. While manufacturers of a product not distributed in the US may have protection from liability, the distributor may be liable.^ieng

Treatment of adenomyosis-associated menorrhagia with a levonorgestrel-releasing intrauterine device.

OBJECTIVE: To evaluate the efficacy and tolerability of treatment with a levonorgestrel-releasing intrauterine device (IUD) in women affected by adenomyosis-associated menorrhagia. SETTING: Tertiary care center. DESIGN: Prospective, open, noncomparative study. PATIENT(S): Twenty-five women aged 38 to 45 years with recurrent menorrhagia associated with adenomyosis diagnosed at transvaginal ultrasonography participated in this study. INTERVENTION(S): An IUD releasing levonorgestel 20 mcg/day was inserted in each patient within 7 days of the start of menstrual flow. All of the patients were requested to compile a pictorial blood loss assessment chart each month. They underwent clinical and transvaginal ultrasound examinations 3, 6, and 12 months after IUD insertion. MAIN OUTCOME MEASURE(S): Menstrual pattern; serum hemoglobin, ferritin, and iron level changes. RESULT(S): One patient experienced IUD expulsion 2 months after device insertion and another requested removal of the IUD 4 months after insertion because of persistent irregular blood loss. Six months after IUD insertion, amenorrhea was observed in 2 patients and oligomenorrhea in another, spotting occurred occasionally in 7, and 13 had scanty but regular flow. One year of follow-up has been completed by the remaining 23 women: 2 with amenorrhea, 3 with oligomenorrhea, 2 with spotting, and 16 with regular flows. Significant increases in hemoglobin, hematocrit, and serum ferritin have been observed, but the lipid metabolism and clotting variables have remained unchanged. CONCLUSION(S): Our findings indicate that marked and safe relief from adenomyosis-associated menorrhagia can be obtained with the use of a levonorgestrel-releasing IUD.

PIP: The efficacy and tolerability of treatment of adenomyosis-related menorrhagia with a levonorgestrel-releasing IUD were investigated in a prospective study of 25 women recruited from a tertiary care center in Italy. All women reported recurrent menorrhagia of at least 6 months' duration and underwent abdominal and transvaginal ultrasonography, hysteroscopy, and endometrial biopsy before study entry. An IUD releasing 20 mcg/day of levonorgestrel was inserted within 7 days of the onset of menses and follow-up examinations were conducted 3, 6, and 12 months after insertion. 1 woman experienced IUD expulsion 2 months after insertion and another requested removal at 4 months because of persistent irregular blood loss. 6 months after IUD insertion, amenorrhea was observed in 2 women, oligomenorrhea in 1 woman, and occasional spotting in 7 women; the remaining 13 women had scanty but regular periods. At 12 months, 2 women reported amenorrhea, 3 had oligomenorrhea, 2 had spotting, and 16 had regular periods. All menstrual anomalies were well tolerated. IUD-related side effects included headache (24%), breast tenderness (16%), seborrhea or acne (24%), and weight gain (28%). Significant increases in hemoglobin, hematocrit, and serum ferritin were recorded; there were no changes in lipid metabolism or clotting variables. These findings suggest that insertion of a levonorgestrel-releasing IUD represents a viable alternative to hysterectomy in the treatment of adenomyosis. It is speculated that the IUD produces deciduation and subsequent marked hypotrophy of eutopic endometrium.

Loss of radiopacity may impede localization of intrauterine contraceptive device.

While ultrasound is the primary modality for localization of an intrauterine contraceptive device, plain films are often employed if the ultrasound examination is negative. A case is reported in which loss of radiopacity hampered identification of an intrauterine device.

PIP: Ultrasonography is the primary method for confirming the intrauterine location of an IUD. When this method fails, a plain radiograph of the pelvis is employed. An IUD not identified on the plain film is presumed to have been expelled. This paper reports a case in which retention of a Progestasert IUD for 9 years was associated with some loss of radiopacity. The search for the IUD in this 30-year-old US woman was prompted by evidence of an actinomycotic infection in endocervical and endometrial curettings obtained during bilateral tubal ligation. Plain films demonstrated a small radiopaque object in the expected location in the uterus. An intact Progestasert IUD was removed without difficulty. Approximately 40% of the barium sulfate originally present had been lost and two small breaks in the polyethylene long arm of the device were identified. If an IUD cannot be identified on plain radiographs despite clinical evidence of its presence, computed tomography should be considered. It is essential that acceptors of the Progestasert system are counseled that the device must be replaced after 1 year.

Long-acting hormonal contraception.

For 30 years, the combined oral contraceptive pill has been an almost automatic choice for effective contraception in sexually active adolescent women. Nevertheless, consideration of the criteria of a hypothetical "ideal" contraceptive suggests that long-acting progestogen-only methods may have considerable advantages for some adolescents. These would include greater efficacy, easier compliance, avoidance of estrogenic side effects, and potentially greater privacy. The disadvantages of menstrual irregularity, progestogenic side effects including weight gain, and the initial greater medicalization of the method, particularly implants, must be weighed against the wishes and preferences of the adolescent. A number of studies of the uptake and utilization of these methods in adolescence have arisen, particularly from the United States. These are reviewed together with experience from programs in the United Kingdom.

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.

The levonorgestrel intrauterine system in the management of menorrhagia.

OBJECTIVE: To assess the effect of a levonorgestrel releasing intrauterine system in the management of menorrhagia. DESIGN: A prospective study. SETTING: A district general hospital in South Wales. METHODS: Fifty women with a failed trial of medical therapy and awaiting hysterectomy or transcervical resection of the endometrium (TCRE) were treated with a levonorgestrel intrauterine system. The menstrual loss was estimated using a modified pictorial chart together with a full blood count and ferritin measurement preinsertion and at three and six to nine months postinsertion. RESULTS: The menstrual loss was reduced to acceptable levels in 37 women at three months and a further four by six to nine months. In all, 41 patients were taken off the waiting list for surgery, four of whom became amenorrhoeic. There was no significant change in full blood count nor ferritin measurement despite unscheduled bleeding for six to eight weeks postinsertion. Fifty-six percent of patients noticed considerable improvement or cure of their premenstrual syndrome symptoms; 80% noted a reduction in dysmenorrhoea. CONCLUSION: The levonorgestrel releasing intrauterine system is an effective nonsurgical treatment for the management of menorrhagia and dysmenorrhoea that has additional benefit as a contraceptive and in relieving premenstrual syndrome.

PIP: A prospective study involving 50 women recruited from a district general hospital in South Wales indicated that the levonorgestrel-releasing intrauterine system (LNG-IUS) represents an effective nonsurgical treatment for menorrhagia and dysmenorrhea. Treatment for menorrhagia with a combination of prostaglandin synthetase inhibitors and antifibrinolytic drugs had failed in these women, and they were on a waiting list for hysterectomy or transcervical resection of the endometrium. Menstrual loss was estimated using a modified pictorial chart and the full blood count and ferritin were measured preinsertion and at 3 and 6-9 months postinsertion. The device was spontaneously expelled in 6 women and almost all subjects experienced some unscheduled bleeding during the first 6-8 weeks postinsertion. Of the 42 women who attended the 3-month visit, 37 were satisfied with the results of the LNG-IUS device and wished to continue; only 5 had no significant reduction in their menstrual scores. Also observed was a reduction in clots and "flooding" and marked improvements in associated dysmenorrhea. 4 women became amenorrheic and 28 were cured of their premenstrual syndrome symptoms. There was no significant change in the full blood count or ferritin. At the 6-9 month visit, 4 of the 5 women who previously reported no change in menstrual scores now reported their menstrual loss was acceptable.