Kerstin Andersson

Levonorgestrel-releasing and copper-releasing (Nova T) IUDs during five years of use: A randomized comparative trial

A 20 micrograms/24 hours levonorgestrel-releasing intrauterine contraceptive device (LNG-IUD) has, in an open randomized multicenter study, been compared to the copper-releasing device Nova T during 5 years of use; 1821 women had the LNG-IUD and 937 women had the Nova T inserted. The 5-year cumulative gross pregnancy rate was 5.9% for Nova T and 0.5% for the LNG-IUD. The local effect of levonorgestrel in the uterine cavity causes reduction of menstrual blood loss and development of oligo-amenorrhea, and the termination rates because of heavy and/or prolonged menstrual flow were significantly (P < 0.001) lower among LNG-IUD users. However, the gross termination rate because of amenorrhea was 6.0 in this group. Hb increased during use of the LNG-IUD and decreased during Nova T use, and the difference between the devices was statistically significant. The incidence of pelvic inflammatory disease (PID) was low in LNG-IUD users regardless of age, whereas in the Nova T group, the PID rate was increased among the youngest women, which makes the difference between the devices significant (P < 0.01). The gross termination rate for reasons considered to be hormonal was 12.1 in the LNG-IUD group compared to 2.0 in the Nova T group (P < 0.001). The LNG-IUD is a long-acting reversible contraceptive method for 5 years with a pregnancy rate comparable to female sterilization. The incidence of PID is low even in young women. In addition, the positive health effects such as decreased menstrual blood loss and increased blood haemoglobin concentration make the LNG-IUD a favorable combination of hormonal and intrauterine contraception.

A comparison of flurbiprofen, tranexamic acid, and a levonorgestrel-releasing intrauterine contraceptive device in the treatment of idiopathic menorrhagia

Treatment with flurbiprofen (100 mg twice a day for 5 days), tranexamic acid (1.5 gm three times a day for 3 days and 1 gm twice a day for another 2 days), and an intrauterine contraceptive device releasing 20 micrograms levonorgestrel per day was compared in women with idiopathic menorrhagia. The menstrual blood loss during two control periods in 15 women subsequently treated with flurbiprofen and tranexamic acid was 295 +/- 52 ml and 203 +/- 25.2 ml in the 16 women later fitted with a levonorgestrel-releasing intrauterine contraceptive device. Menstrual blood loss was reduced by all three forms of treatment. The reduction in menstrual blood loss expressed as a percentage of the mean of two control cycles for each form of treatment was as follows: flurbiprofen, 20.7% +/- 9.9%; tranexamic acid, 44.4% +/- 8.3%; levonorgestrel-releasing intrauterine contraceptive device after 3 months, 81.6% +/- 4.5%; levonorgestrel-releasing intrauterine contraceptive device after 6 months, 88.0% +/- 3.1%; levonorgestrel-releasing intrauterine contraceptive device after 12 months, 95.8% +/- 1.2%. The reduction in menstrual blood loss achieved by the levonorgestrel-releasing intrauterine contraceptive device was greater than that recorded with flurbiprofen (p less than 0.001) and tranexamic acid (p less than 0.01), and was greater for tranexamic acid when compared with flurbiprofen (p less than 0.05). The levonorgestrel-releasing intrauterine contraceptive device was the only form of treatment to reduce mean menstrual blood loss below 80 ml per menstruation, the upper limit of normal menstrual blood loss.

Perforations with intrauterine devices. Report from a Swedish survey.

This survey comprised 50 consecutive perforations occurring with intrauterine devices (IUD) reported to the National Patient Insurance Scheme Register during 1990 to 1993. All 50 women were parous and > 20 years of age at the time of IUD insertion. Forty-two (84%) of the IUD were inserted by a midwife and eight by a gynecologist. A total of 45 women (90%) had their IUD inserted < 1 year after a full-term pregnancy and 31 women (62%) had their IUD inserted < or = 12 weeks after delivery. Of the 50 women, 27 (54%) reported that they were breastfeeding at the time of IUD insertion. No particular IUD was overrepresented in relation to its share on the market. In 31 cases (62%), severe pain at insertion and during the first 24 h was recorded. In 14 women (28%), the perforation was diagnosed early (i.e., within 1 month of insertion) and in 36 women (72%), the perforation was diagnosed > 1 month after insertion. Lower abdominal pain was the most frequent symptom at early diagnosis but in two cases, the main symptom was heavy bleeding. Among the 36 women in whom the perforation was discovered more than 1 month after insertion, the diagnosis was made when an unexpected pregnancy occurred in 20 women (56%). In 15 cases, the IUD strings were not visible during pelvic examination at a routine check-up, which led to efforts to locate the IUD. Thirty-two women (64%) underwent laparotomy for removal. We conclude that lactating women seem to be a risk group for perforation and that a national register of IUD perforations could provide a better means of quality control.

Effective contraception with the levonorgestrel-releasing intrauterine device: 12-month report of a European multicenter study

The use-effectiveness of an intrauterine contraceptive device releasing 20 mcg of levonorgestrel daily (Lng-IUD), and of a Nova T copper-releasing IUD, were studied in a randomized, comparative multicenter trial. The Lng-IUD was inserted in 1821, and the Nova T in 937 women. The 12-month net pregnancy rate with the Lng-IUD (0.1 per hundred women) was significantly lower than that with the Nova T (0.9 per hundred). Removal rates for menstrual problems and/or pain were similar for the two methods (net rates 7.5 and 8.7, respectively). The 12-month continuation rates were 82.2 for the Nova T and 79.7 for the Lng-IUD. The reduction of the bleeding led to oligomenorrhea and amenorrhea in users of the Lng-IUD; the removal rate for these reasons was 1.4. The removal rate for hormonal side effects with the Lng-IUD was 2.4. Blood hemoglobin concentrations increased among users of the Lng-IUD and decreased among users of the Nova T. The results show that the Lng-IUD was a highly effective contraceptive method which reduced menstrual bleeding. It is a promising alternative for women desiring a highly effective method for long-term use.

Return to fertility after removal of a levonorgestrel-releasing intrauterine device and Nova-T

In a European randomized multicenter study, the efficacy and safety of an intrauterine contraceptive device releasing 20 microgram levonorgestrel/24 hours (LNG-IUD) have been evaluated and compared to the Nova-T. Because the LNG-IUD has a strongly suppressive effect on the endometrium and in some women affects ovarian function, the return to fertility after removal of the IUD was studied. Two-hundred-nine women (71 in the Nova-T and 138 in the LNG-IUD group), who had their IUDs removed because of planning pregnancy, were followed at least 24 months or until termination of pregnancy. For the Nova-T, the cumulative conception gross rate was 71.2/100 women after 12 months (79.7 after 24 months) and for the LNG-IUD 79.1 (86.6 after 24 months). The difference between the devices is not statistically significant, and in spite of the endometrial suppression during use of LNG-IUD, there is no delay of return to fertility and in both groups 96% of the pregnancies occurred during the first year after removal of the device. Eighty-four % of the pregnancies in the Nova-T group and eighty-six % in the LNG-IUD group ended in live births. The results suggest that the endometrium recovers quickly, normal ovulations are established and the fertility seems to be unaffected after use of an LNG-IUD.

The Influence of the Gyne-T 380s IUD on Menstrual Blood Loss and Iron Status

The influence of the Gyne-T 380S intrauterine contraceptive device (IUD) on menstrual blood loss (MBL) and iron status (hemoglobin, hematocrit, red cell count and indices, and serum ferritin) was evaluated. MBL was determined objectively by the alkaline hematin method in 18 women (mean age 37.1 +/- 1.6 yr, range 22-46 yr) before and 3, 6 and 12 months after insertion of a Gyne-T 380S IUD. MBL prior to IUD insertion was 59 +/- 8 ml and increased to 91 +/- 11 ml (p < 0.01) 3 months after insertion. MBL then remained largely unchanged during the remainder of the observation period (6 months, 94 +/- 12 ml; 12 months, 92 +/- 13 ml). The percentage increase in MBL at the respective measurement points ranged between 54 and 59% which is comparable with previous reports regarding the increase in MBL associated with the use of a copper IUD. There were no significant changes recorded in iron status parameters during the 12-month observation period following IUD insertion. Based on the results of the present study, women from developed countries apparently tolerate an increased MBL of approximately 55% without developing iron deficiency anemia. Iron stores were unchanged indicating an adequate adaptive increase in intestinal iron absorption.

Identification of Novel α-Synuclein Isoforms in Human Brain Tissue by using an Online NanoLC-ESI-FTICR-MS Method

Parkinson’s disease (PD) and Dementia with Lewy bodies (DLB) are neurodegenerative diseases that are characterized by intra-neuronal inclusions of Lewy bodies in distinct brain regions. These inclusions consist mainly of aggregated α-synuclein (α-syn) protein. The present study used immunoprecipitation combined with nanoflow liquid chromatography (LC) coupled to high resolution electrospray ionization Fourier transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS/MS) to determine known and novel isoforms of α-syn in brain tissue homogenates. N-terminally acetylated full-length α-syn (Ac-α-syn1–140) and two N-terminally acetylated C-terminally truncated forms of α-syn (Ac-α-syn1–139 and Ac-α-syn1–103) were found. The different forms of α-syn were further studied by Western blotting in brain tissue homogenates from the temporal cortex Brodmann area 36 (BA36) and the dorsolateral prefrontal cortex BA9 derived from controls, patients with DLB and PD with dementia (PDD). Quantification of α-syn in each brain tissue fraction was performed using a novel enzyme-linked immunosorbent assay (ELISA).

Intrauterine administration of levonorgestrel 5 and 10 μg/24 hours in perimenopausal hormone replacement therapy: A randomized clinical study during one year

Objective. To investigate the clinical effects especially with regard to histopathology and bleeding patterns by levonorgestrel (5‐ or 10 ug/24 h) released from an intrauterine system (IUS) in combination with estradiol valerate (2 mg) given daily or transdermal estradiol (50 μg/24 h) in perimenopausal women.OBJECTIVE To investigate the clinical effects especially with regard to histopathology and bleeding patterns by levonorgestrel (5- or 10 microg/24 h) released from an intrauterine system (IUS) in combination with estradiol valerate (2 mg) given daily or transdermal estradiol (50 microg/24 h) in perimenopausal women. DESIGN A prospective randomized single blind comparison during twelve months. SUBJECTS One hundred and twelve perimenopausal women with vaso-motor symptoms. OUTCOME MEASURES Histopathological assessment of the endometrium, ultrasonographic measurement of endometrial thickness, bleeding patterns, and acceptability. RESULTS A total of 108 women started the study and 12 discontinued. The most common reason for discontinuation was frequent bleeding (six women). Thus, 96 (89%) women were followed for twelve months. In both the 5- and 10 microg levonorgestrel IUS groups the endometrium in all women but one was non-proliferative after twelve months and no case of hyperplasia was found. Irregular bleeding was reported during the first months of treatment but decreased after six months. At the end of the study 62% in the 5 microg- and 61% in the 10 microg group were amenorrhoic. The effects on bleeding patterns did not differ between the two levonorgestrel dosages. CONCLUSION Continuous combined HRT was well accepted in perimenopausal women when the progestogen was given in an IUS. IUSs releasing 5- or 10 microg/24 h levonorgestrel seemed to minimize the progestogenic side effects and proved to be sufficient for effective prevention of endometrial stimulation by estrogen treatment in HRT in perimenopausal women.

Use of hormone replacement therapy.

NHS hospital Honorary hospital Total no of Women honspltal Women honorary Total no of X NHS-appolnted %of all honorary consultants consultants NHSappolnted consultants hospltal consultants NHS appointed hospltal consultants consultants who (total n) (total) hospital (total) (total) women hospital who are women are women consultants consultants 1991 1584

HORMONAL INTRAUTERINE DEVICES

Intrauterine administration of progestogens from an IUD was introduced more than 15 years ago in order to improve the contraceptive efficacy and to reduce side-effects. A device releasing 20 micrograms levonorgestrel daily (Levonova) with a life span of at least 5 years is now available and has been subjected to an extensive study including 1821 women followed during 5 years. The safety and efficacy were evaluated in comparison to Cu-T IUDs. The pregnancy rate (Pearl index) was 0.09. During the first two cycles after insertion intermenstrual bleeding was common, otherwise the frequency of side-effects was low. The results seem to justify the conclusion that intrauterine administration of progestogens represents a further development of IUDs and hormonal contraception. Furthermore, these devices have proven to be effective in treatment of heavy menstrual blood losses. In many menorrhagic women, use of these IUDs can replace more invasive surgical methods such as hysterectomy or endometrial resection. Intrauterine administration of progestogens is also effective in opposing the proliferative effect of oestrogen on the endometrium in women on hormonal replacement therapy.