G. Freundl

Cycle characteristics after discontinuation of oral contraceptives.

Nearly 60% of the women between 20 and 40 years of age who do not want to conceive choose oral contraceptives (OCs) for contraception in Germany. In an ongoing prospective study on the use of natural family planning in Germany, 175 women have been observed for 3048 cycles immediately after having discontinued OCs (post-pill group). They were compared to a control group of 284 women observed for 6251 cycles, who had never taken OCs. Both groups were comparable in age and sociodemographic characteristics. After discontinuing OCs, 57.9% of all first cycles were ovulatory with sufficient luteal phases. However, for the total post-pill group the cycle length was significantly prolonged up to the ninth cycle. A significantly higher number of luteal phases were insufficient in the post-pill group. Major cycle disturbances (cycle length > 35 days or luteal phase of < 10 days of elevated basal body temperature or anovulatory cycles) were significantly more frequent in the post-pill group up to the seventh cycle. Cycle disturbances after discontinuing OCs were reversible but the time of regeneration took up to 9 months (significant) or even longer (not significant). These results will help to counsel couples who wish to conceive after discontinuing OCs or who want to continue contraception with alternative methods.

Steroidal 'add-back' therapy in patients treated with GnRH agonists.

GnRH analogues (GnRH-a) are well established in the treatment of endometriosis. However, due to hypooestrogenic effects, treatment is limited to 6 months. The aim of this randomized, double-blind, comparative study was to evaluate whether symptoms and signs of hypooestrogenism, e.g. hot flushes, sweating and sleeplessness, could be avoided by a steroidal add-back regimen, while the beneficial effect of a GnRH-a on endometriosis could be maintained. In group A, 14 patients were treated with 3.75 mg leuprorelin acetate depot per month i.m. in combination with 20 mg ethinyloestradiol plus 0.15 mg desogestrel orally for 3 weeks. In group P, 13 patients received leuprorelin acetate, following the same schedule as in group A, and placebo. Treatment duration was 6 months. At first-look laparoscopy (postoperatively) group A had an r-AFS score of 23.57 and group P of 24.23. After 6 months of treatment with leuprorelin acetate depot r-AFS scores had dropped to 16.14 in group A and to 6.25 in group P at second-look laparoscopy, achieving statistical significance in both groups (p < 0.001). Hypooestrogenic adverse drug reactions (e.g. hot flushes, sweating and sleeplessness) were more frequently reported in group P, whereas the occurrence of headache was comparable in both groups. Dysmenorrhoea was significantly reduced in both groups, whereas dyspareunia was only decreased in group P. Variations in laboratory values were within normal ranges and did not give any concern about drug safety. Loss of bone mineral density caused by the GnRH-a was reduced by the combined oestrogen/progestin add-back therapy. In conclusion, this therapy can lead to a reduction in hypooestrogenic adverse drug reactions and mostly preserves agonist efficacy with the chance of treatment prolongation.

Retrospective Clinical Trial of Contraceptive Effectiveness of the Electronic Fertility Indicator Ladycomp/Babycomp

The Babycomp/Ladycomp (Valley Electronics Ltd., Eschenlohe, Germany) is an electronic device that combines the temperature method and calendar method for planning and preventing pregnancy by identifying the fertile and infertile phases of the menstrual cycle.In a retrospective clinical trial, the system was tested as a contraceptive aid. A total of 648 women from Germany and Switzerland have participated: 597 women with 10 275 months of use used the device for contraception. Thirty-three unplanned pregnancies were identified, giving a total pregnancy rate of 3.8 use effectiveness according to the Pearl Index. Six method-related pregnancies occurred, producing a method Pearl Index of 0.7. Calculating the cumulative pregnancy rates by life-table analysis, it was found that, after about one year of exposure, the probability of an unintended pregnancy was 5.3% (0.053), after 2 years it was 6.8% (0.068) and after about 3 years of exposure it was 8.2% (0.082). The mean length of the identified fertile period was 14.3 days with a standard deviation of 4.6 days in all cycles reported. The acceptance of the device by the woman and her partner was good. In fact, 21 of the 33 women who became pregnant would still recommend the device for further use (63.6%).

Development of the first urinary reproductive hormone ranges referenced to independently determined ovulation day.

Abstract Background: Urinary hormone level analysis provides valuable fertility status information; however, previous studies have not referenced levels to the ovulation day, or have used outdated methods. This study aimed to produce reproductive hormone ranges referenced to ovulation day determined by ultrasound. Methods: Women aged 18–40 years (no reported infertility) collected daily urine samples for one complete menstrual cycle. Urinary luteinising hormone (LH), estrone-3-glucuronide (E3G, an estradiol metabolite), follicle stimulating hormone (FSH) and pregnanediol-3-glucuronide (P3G, a progesterone metabolite) were measured using previously validated assays. Volunteers underwent trans-vaginal ultrasound every 2 days until the dominant ovarian follicle size reached 16 mm, when daily scans were performed until ovulation was observed. Data were analysed to create hormone ranges referenced to the day of objective ovulation as determined by ultrasound. Results: In 40 volunteers, mean age 28.9 years, urinary LH surge always preceded ovulation with a mean of 0.81 days; thus LH is an excellent assay-independent predictor of ovulation. The timing of peak LH was assay-dependent and could be post-ovulatory; therefore should no longer be used to predict/determine ovulation. Urinary P3G rose from baseline after ovulation in all volunteers, peaking a median of 7.5 days following ovulation. Median urinary peak E3G and FSH levels occurred 0.5 days prior to ovulation. A persistent rise in urinary E3G was observed from approximately 3 days pre- until 5 days post-ovulation. Conclusions: This study provides reproductive hormone ranges referenced to the actual day of ovulation as determined by ultrasound, to facilitate examination of menstrual cycle endocrinology.

Effects of Add-Back Therapy on Bone Mineral Density and Pyridinium Crosslinks in Patients with Endometriosis Treated with Gonadotropin-Releasing Hormone Agonists

Treatment of endometriosis with gonadotropin-releasing hormone agonists (GnRHa) is limited to 6 months because of possible adverse effects on bone metabolism. We designed a randomized, double-blind, placebo-controlled, prospective study of 27 patients with endometriosis who were given GnRHa with or without hormone add-back therapy (+ 20 µg of ethinyl estradiol with 0.15 mg desogestrel) designed to suppress the adverse effects of hypoestrogenism while preserving the efficacy of GnRHa. Both regimens showed significant improvements in endometriosis, dysmenorrhea, and pelvic pain; effects were significantly better in the GnRHa + placebo group. The GnRHa + placebo group had significantly higher serum calcium levels and a significantly higher loss of lumbar spine bone mineral density (BMD). Urinary levels of pyridinium crosslinks increased significantly in the GnRHa + placebo group, and declined to normal in the GnRHa + add-back group. The add-back therapy protects women taking GnRHas from severe loss of BMD and accelerated bone collagen resorption, but reduces the efficacy of the GnRHa.

Results of an Efficacy-Finding Study (EFS) with the Computer-Thermometer Cyclotest 2 Plus Containing 207 Cycles

Prospectively collected cycles of 207 women were used to find out the efficacy of the Cyclotest 2 plus algorithm in detecting the fertile time in a womans cycle. The results of the device were compared with the beginning and the end of the fertile time identified by the symptothermal method (STM) of natural family planning (NFP). It was found that the algorithm led to dangerous reduction of the fertile time (FT) in only 2 out of 207 woman cycles (0.96%). However, at the end of fertile time (FE) the device requested more abstinence than was necessary in about 12% of the cycles. We feel that more research should be performed on detecting the end of the fertile time.