Progesterone-releasing Intrauterine Device Research Articles

Two cases of uterus-conserving treatment for early stage endometrial cancer

The aim of study is to present two successful cases of conservative surgical treatment of women with early-stage endometrial cancer who desired to have fertility in the two cases. A 32-year-old nulligravid woman had Stage IA endometrial cancer which was a 1.5-cm sized lesion confined to the left fundal side of the uterus. The other 35-year-old nulligravid woman had a 2-cm sized lesion suspicious for deep myometrial involvement suggesting Stage IB endometrial cancer. The women underwent hysteroscopic complete resection of tumor with safe resection margin just after laparoscopic tubal ligation, followed by insertion of a progesterone-releasing intrauterine device. The patients have no evidence of recurrence for 26 months and 27 months of follow-up, respectively. Hysteroscopic complete resection of tumor with safe margin combined with bilateral tubal ligation, followed by a progesterone-releasing intrauterine device could be a good option for early-stage endometrial cancer.

Therapy Insight: guidelines for selection of contraception in women with rheumatic diseases

Use of contraceptives by women with rheumatic diseases, especially those with systemic lupus erythematosus, has long been thought to carry risks, such as disease exacerbation, thrombosis and other adverse effects. The use of effective contraception has, therefore, been avoided, despite many affected women being of reproductive age. Knowledge of risks and benefits of contraceptive methods in the general population has improved, as have the safety and effectiveness of hormonal contraceptives. Methods of administration have evolved and now include transdermal and intravaginal routes, a progesterone-releasing intrauterine device, and an extended-cycle oral contraceptive. Birth control pills are not all alike; the risk of adverse effects varies depending on the amount of estrogen and type of progestin used. Data show that patients with stable systemic lupus erythematosus are not at increased risk of disease flare while taking standard oral contraceptives. Despite a lack of randomized studies, evidence strongly suggests that the elevated risk of thrombosis makes estrogen-containing contraceptives unsuitable for patients with antiphospholipid antibody. Other important issues include potential interactions between hormonal contraceptives and other medications and possible risk of infection if an intrauterine device is used. Rheumatologists are increasingly working with gynecologists and patients to make choices about which contraceptive methods to use. Decisions should be individualized according to the patient's medical status, personal preference, and stage of reproductive life.

Endometrial Histology, Uterine Bleeding, and Metabolic Changes in Postmenopausal Women Using a Progesterone-Releasing Intrauterine Device and Oral Conjugated Estrogens for Hormone Replacement Therapy

Seven normal postmenopausal volunteers were enrolled in an 18-month study to evaluate a progesterone-releasing intrauterine device (P-IUD) used in conjunction with oral conjugated estrogen to control uterine bleeding and inhibit the endometrial effect of estrogen. Serum estradiol (E2) levels were elevated over baseline in all women throughout the course of the study. Serum progesterone (P4) did not change significantly after the insertion of the P-IUD. Endometrial thickness by ultrasound was <9.0 mm throughout the course of the study. Endometrial histology was interpreted as marked progesterone effect (decidualization) in all of the endometrial biopsies obtained at 6, 12, and 18 months. Uterine bleeding was infrequent after the third month after insertion of the P-IUD in all but one of the volunteers. Serum lipids obtained at 6 and 12 months showed an increase in triglycerides between these two intervals but no change in serum cholesterol. Two of the six volunteers had a decrease in HDL2 cholesterol, which is unexplained. Bone densitometry determinations of the lumbar spine and femoral neck showed an increase during the course of the study. The P-IUD was acceptable to the volunteers, and based on these data, appears effective in inhibiting the estrogen effect on the endometrium and reducing uterine bleeding. These attributes make targeting delivery of progesterone to the endometrium an attractive method for hormone replacement therapy.

The effect of the progesterone-releasing intrauterine device on uterine endometrium and fallopian tube epithelium.

A scanning and transmission electron microscopy study was undertaken of the effect of the progesterone releasing intrauterine device (Progestasert, Alza Corporation, USA) on the uterine endometrium and fallopian tube epithelium. Small erosions of surface epithelium and microthrombosis of stromal capillaries were found in the endometrium below the inert part of the device. A reduction of ciliated cells and shortened cilia were seen in the endometrium below the active part of the device and large dilated venules were present in the underlying stroma. Fallopian tubes from IUD patients contained fewer ciliated cells than those of the controls. The morphological changes described are likely to be major factors responsible for the irregular bleeding which occurs with Progestasert IUDs and the possible increase in tubal pregnancy.

Endometrial estrogen and progestin receptors in women bearing a progesterone-releasing intrauterine device

Endometrial biopsies were obtained from eleven volunteers bearing a progesterone-releasing intrauterine device (IUD). The mean treatment time was 4.1 yrs (range 1–5 yrs). Tissue samples were collected during the follicular phase of the cycle and assayed for estrogen and progestin receptors with [ 3H]estradiol and [ 3H]ORG 2058 (16α-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione) as the respective radioactive ligands. Both receptor values were significantly lower (p < 0.01) than those present in endometrial tissue of normally menstruating women. The steroid receptor concentrations measured (estrogen receptor 19.6 ± 9.9 and progestin receptor 134.4 ± 121.4 fmol/mg cytosol protein) from women with an IUD represented only about 20 % of those in endometria of normal women. This result suggests that progesterone released from the IUD has a depressive action on the sex steroid receptor levels which may contribute to the contraceptive effectiveness of the IUD.

Carbohydrate and Lipid Studies in Women Using the Progesterone Intrauterine Device for One Year

Carbohydrate and lipid metabolism was evaluated in 31 women before and after 1 year’s use of a progesterone-releasing intrauterine device. The studies involved measuring blood glucose and plasma insulin levels during a 3-hour oral glucose tolerance test and also measuring fasting cholesterol and triglyceride levels. There was no change in the cholesterol levels, whereas the triglyceride concentration was lower at the 1-year test. The blood glucose values were unchanged at four of the time periods, whereas the 3-hour value was elevated at the 1-year test. The plasma insulin values were increased in the fasting, 0.5-, and 3-hour samples at the 1-year test. The increased insulin secretion needed to maintain the blood glucose concentration suggests that the released progesterone may have a systemic effect.

A prospective study of plasma prolactin levels in women using the progesterone releasing intrauterine device (P-IUD)

Plasma prolactin levels were measured by a radioimmunoassay technique in twenty-six women before and after six and twelve months of using a progesterone type intrauterine device. The results show no significant change in the prolactin levels and do not support a systemic effect of either the intrauterine device or the released progesterone.

Effects of the progestasert® on the menstrual pattern, ovarian steroids and endometrium

Clinical studies with the new progesterone-releasing intrauterine device (Progestasert) were done in 192 women with follow-ups at 6 and 12 months, accumulating a total of 1,823 women months. 108 were nulliparous and 84 were parous. Our study shows 0.5 pregnancies per 100 women years during the first 12 months of its use, which is considerably lower than previously reported. The overall expulsion rate was 7.4 per 100 women years, with 4.8 and 10.7 corresponding to nulliparous and parous women, respectively. It was of significance to note that most expulsions (77%) occurred within one month after insertion. Intermenstrual spotting or bleeding constituted the major side effect of the system; yet, the amount was small and mostly limited to the first two months of its use. It was observed that the amount of menstrual flow and dysmenorrhea were significantly reduced in 20–30% of patients, including those women who had a history of heavy menstrual flow and dysmenorrhea prior to the insertion of the Progestasert. The overall continuation rate was 76.0 ± 3.2 with 79.2 ± 4.1 for the nulliparous women, and 71.7 ± 5.0 for the parous; thus the Progestasert is evidently suitable for both nulliparous and parous women. Serum steroid assays showed a normal ovulatory function. The effect of the Progestasert on the endometrium was observed in biopsies performed at 12 months, which generally displayed glandular atrophy and decidual reaction, regardless of the phase of the cycle. The new concept of combining IUDs with locally delivered steroidal compounds offers advantages, but the long range results rely on continuous clinical observations comprising a large population of many years of use.

Intrauterine contraception with the progesterone-T device: Interference with the metabolic activity and capacitation of spermatozoa

The possible mechanism of action of the progesterone-releasing intrauterine device has been studied by means of determination of the action that uterine washings have on the metabolism and capacitation of human and rabbit spermatozoa. Uterine washings from normal, untreated women, induce, in human spermatozoa, the same changes although of lesser magnitude, that have been previously reported as possibly participating in the uterine stage of capacitation. Uterine washings obtained from progesterone-T wearing women produce a significant decrease in oxygen uptake and glucose utilization, an inhibition of the BANA-hydrolytic activity, and changes in the tetracycline binding and release processes. All these changes support the hypothesis that at least part of the mechanism of action of the progesterone-releasing type of intrauterine devices is due to a direct capacitation inhibiting effect of the uterine secretion. This hypothesis is strengthened by the direct demonstration of inhibition of in vitro rabbit spermatozoa capacitation produced by these washings.