Altered uterine artery blood flow impedance after danazol therapy: possible mode of action in dysfunctional uterine bleeding.

OBJECTIVE: To test the hypothesis that danazol increases the impedance to uterine circulation and hence reduces the effective uterine blood flow after a predetermined period of therapy. DESIGN: Prospective, longitudinal study. SETTING: Reproductive medicine unit of a university teaching hospital. PATIENT(S): Eight premenopausal women with dysfunctional uterine bleeding. INTERVENTION(S): Six weeks of danazol therapy. MAIN OUTCOME MEASURE(S): The uterine artery blood flow impedance as indicated by the pulsatility and resistance indices; the hormonal profile (E2, FSH, and LH levels); the uterine dimensions (length, width, anteroposterior diameter, and area); and the endometrial thickness. RESULT(S): The indices of uterine artery impedance were significantly increased after danazol therapy, indicating a possible reduction in the effective uterine artery blood flow. There was no statistically significant change in the hormonal profile, uterine dimensions, or endometrial thickness. CONCLUSION(S): Danazol therapy for 6 weeks results in a significant increase in the uterine artery impedance and hence a possible reduction in the effective uterine artery blood flow. This may explain in part its efficacy in the management of dysfunctional uterine bleeding and in the preoperative preparation of women undergoing endoscopic endometrial ablation. The exact mechanism for its action in this regard remains to be determined but appears to be independent of E2 levels. This preliminary finding may help in monitoring the treatment of dysfunctional uterine bleeding, preoperative and postoperative investigation of women undergoing endoscopic endometrial ablation, and the development of alternative treatment strategies for dysfunctional uterine bleeding in the future.

Modulation of uterine artery resistance to blood flow by the oral contraceptive pill.

The changes in uterine artery resistance to blood flow were studied during a normal ovulatory cycle (control) and during a cycle on the combined oral contraceptive pill in 10 healthy women, aged 18-35 years, using transvaginal color Doppler imaging. Ovulation was monitored using ultrasound and hormonal assays during both cycles. The Pulsatility Index (PI) was used as a measure of uterine artery resistance, on days 8 (midproliferative) and 22 (midluteal) of the control cycle and on days 22 (maximal ovarian suppression) and 28 (minimal ovarian suppression) of the pill cycle. During the pill cycle, the uterine artery resistance decreased from a mean PI = 4.37 (range 2.4-7.95) on day 22 to a mean of 2.79 (1.94-4.99) on day 28, p = 0.006. The uterine artery resistance was significantly higher on day 22 during the pill cycle compared to the same day of the control cycle, p < 0.0001. Anovulatory cycles on the oral contraceptive pill are associated with an increase in uterine artery resistance and a decrease in uterine perfusion, this effect being reversed during the pill-free week.

Three successive pregnancies in a patient with Takayasu's arteritis.

Takayasu's arteritis is a rare non-specific obliterative panarteritis of unknown origin that occurs predominantly in young Asian and Oriental females of childbearing age and has been encountered in the UK. With the exception of a few large series from the Far East, much of the information on Takayasu's arteritis in pregnancy comes from isolated case reports with no long term follow-up after pregnancy. We report a patient with this condition who had three pregnancies during a 4-year follow-up period with no serious complications.

Indices of differential endometrial: myometrial growth may be used to improve the reliability of detecting endometrial neoplasia in women on tamoxifen.

The aim of this study was to test the hypothesis that the use of indices of differential endometrial: myometrial growth may be a non-invasive method of improving the reliability of detecting endometrial neoplasia in women on tamoxifen. Thirty postmenopausal women were involved in this prospective study. Nineteen had been treated with tamoxifen for 2 years or more, and eleven were age- and ponderal index-matched controls who had never been exposed to tamoxifen and who were non-smokers. Transvaginal ultrasonography and color Doppler imaging were performed, to measure the length, anteroposterior diameter, uterine sagittal area, endometrial thickness and uterine blood flow (using the pulsatility index and the resistance index as measures of uterine blood flow impedance). The anteroposterior diameter: endometrial thickness ratio and product, and the saggital area: endometrial thickness ratio and product were used as indices of differential endometrial: myometrial growth. The predictive values (sensitivity, specificity, positive and negative predictive values) of each index were calculated using established criteria. For the purpose of analysis the women were allocated to three groups: controls (group 1); women on tamoxifen without endometrial neoplasia (group 2) and women on tamoxifen who developed endometrial neoplasia (group 3). The mean age was similar in the three groups as was the duration of tamoxifen treatment in groups 2 and 3. Analysis of the decision matrix based on increased endometrial thickness (> 5 mm) alone revealed good sensitivity (100%) and negative predictive value (100%) but poor specificity (46.15%) and positive predictive value (26.32%). However, when the indices of differential endometrial: myometrial growth were taken into consideration, the sensitivities and negative predictive values were similar but the specificities and positive predictive values were significantly improved, indicating an improvement in the reliability of predicting the development of endometrial neoplasia.

Short communication: the effect of mode of delivery on contractile function of placental arteries in vitro.

This study was designed to determine the effect of the mode of delivery on the in vitro assessment of placental blood vessel function. Twenty-two subjects with uncomplicated pregnancies, normal antenatal Doppler flow velocity waveforms and normal birth weights were recruited for the study. The 11 subjects who were delivered by elective caesarean section were matched with 11 controls, who had uncomplicated labours and spontaneous vaginal delivery. Two tertiary chorionic plate arteries were dissected free 1 h after delivery and mounted in a myograph. Cumulative concentration response curves were constructed to the thromboxane A2 analogue U46619, prostaglandin F2 alpha and angiotensin II. After a period of 12 h a further two vessels were mounted and a concentration response curve to U46619 was repeated to determine whether a delay of several hours after delivery would have an effect on the responses of these vessels. These placental arteries constrict to U46619, prostaglandin F2 alpha and angiotensin II in a dose-dependent manner. There was no statistical difference in the maximum contractile responses or pD2 values between the different modes of delivery. A delay in dissection of up to 12 h had no effect on the maximum response or pD2 with U46619. Therefore, contractile function of placental arteries is unaffected by mode of delivery or a delay in dissection.

Luteinizing hormone releasing hormone agonist for contraception in breast feeding women.

During the period of lactation there is a need for a reliable method of contraception since the suppressive effects of lactation on ovulation decline as the duration of breastfeeding is decreased. The aim of this study was to establish that chronic treatment with a LHRH agonist would prevent ovulation throughout the period of lactation and to evaluate the effects of the treatment on estrogen production, bleeding patterns, and nursing practice. Starting 6 weeks postpartum, nine mothers took 300 micrograms LHRH agonist (buserelin), intranasally once daily for the remainder of the duration of breastfeeding [216 +/- 18 days (mean +/- SEM)]. Urinary excretion of LH, estrone, and pregnanediol was compared to that of nine control breastfeeding mothers. In the control subjects follicular development, as assessed by rises in estrone, was minimal during the first 90 days of the study. Thereafter, phases of estrogen secretion were observed. Ovulation occurred in seven of the nine mothers on one to six occasions; time to first ovulation varied from 90-296 days. In the women taking buserelin, LH and estrone were initially stimulated for 1 and 2 weeks, respectively, then declined to basal levels. No ovulations occurred in the treated group. In six treated mothers only minor fluctuations in estrone were observed during the remainder of agonist treatment. In three subjects more frequent and sustained episodes of estrogen secretion were observed, but in contrast to the controls the rises in estrone were not followed by a typical LH surge or a rise in pregnanediol. Bleeding occurred in eight of the nine of the control mothers on one to seven occasions during the study period. The first bleed in five of the mothers was anovular, while other menstrual bleeds occurred in response to falling levels of pregnanediol. Of the mothers taking buserelin, one was amenorrhoeic, and five had only one light bleeding associated with the initial stimulation of estrone. Of the three women with continued fluctuations of estrone, one had three light bleeds, one experienced frequent spotting, while one had regular bleeding. No other side-effects, such as hot flashes or changes in nursing practices, were reported. Our results indicate that LHRH agonist treatment has the potential to be developed as an acceptable method of contraception during the postpartum period. The duration of treatment may be long enough to have a significant effect on maternal-infant well-being without encountering significant problems associated with low estrogen output.

Contraception and lactation.

PIP: Lactation's contraceptive effect cannot be relied upon for more than 6 weeks postpartum, and ovulation often occurs in advance of the 1st postpartum menstrual period. Although breastfeeding mothers should adopt a contraceptive method, care must be taken to select a method that will not adversely affect the production and composition of breast milk. Of greatest concern is the effect of synthetic hormones transmitted via breast milk on the developing infant. Possible alternatives are the Billings ovulation detection natural family planning method, diaphragms and caps, IUDs, and sexual sterilization. While combined oral contraceptives (OCs) are contraindicated because of their harmful effects on the fat and protein composition of breast milk and on milk production, the progestogen-only OC does not appear to interfere with the quality of breast milk and less than 0.1% of the progestogen passes on to the infant. Depo-Provera, and other injectable progestogens, appear to be appropriate for breastfeeding women, although the 1st injection should be postponed until 6 weeks postpartum to reduce the likelihood of heavy bleeding. Under investigation is a nasal spray containing buserelin, a luteinizing hormone-releasing hormone agonist, that shows promise as a reliable, acceptable, and easily administered nonsteroidal contraceptive that does not interfere with lactation. A biodegradable buserelin implant, which would last as least 3 months, also is being developed and would be especially useful in developing countries where storage of a nasal spray might be problematic.^ieng

LRH agonist buserelin as a post-partum contraceptive: lack of biological activity of buserelin in breast milk.

To evaluate the possibility of using the LRH agonist buserelin as a contraceptive for lactating women we have investigated the passage of buserelin into breast milk and explored possible biological activity in the infant. Eleven mothers received 600 micrograms buserelin by nasal spray. Buserelin was measured by radioimmunoassay in the breast milk of these mothers, and values ranged from undetectable levels (less than 15 pg/ml) to 8800 pg/ml. The maximum amount of buserelin that an infant could ingest during an average feed would be 1-2 micrograms. In adult men ingestion of 600 micrograms buserelin dissolved in cows milk was without biological effect upon both serum and urinary levels of luteinizing hormone. There was no change in the levels of LH found in the urine of infants fed by women who had received 600 micrograms buserelin by nasal spray. We conclude that the small amount of buserelin passing into the breast milk of these volunteers was without biological activity when ingested by the infant.