[Long-term side-effects following cyproterone acetate containing therapy in gynecology]. / Langzeitnebenwirkungen nach cyproteronacetathaltiger Therapie in der Gynäkologie.

It has been suggested that cyproterone acetate (CPA) has a mutagenic potency. It has been postulated that a threshold dosage of CPA has mutagenic effects, but in the same way data have been published documenting that a continuous low dosage of cyproterone acetate leads to a reduction of mutagenic episodes. Despite published data about higher levels of DNA adduct creations due to CPA an international multicentre study analysing 2,506 patients with 7,971 patient-years that used CPA could not find any liver cell cancers, even if due to epidemiological data 6 liver cell cancers should have occurred upon this study group. The present study deals with the evaluation of 57 women which received CPA in combination with EE2 11-13 years before. The daily dosage was 2 mg CPA in combination with 35 mg or 50 mg EE2. In Germany these drugs were registered under the name of Diane 35 or Diane 50. Long-term follow-up evaluation concerning side effects, especially the appearance of liver cell carcinomas, were the aim of this study. With the records of 32% (18/57) of the above mentioned patient group the following long-term follow-up side effects could be observed: 1) weight gain, 2) headache, 3) migraine, 4) gastrointestinal disorders, 5) mood affections/depressions, 6) oedema of the legs, 7) skin affections, 8) mastodynia. No benign liver tumor or liver cell carcinoma was detected upon our group of investigated patients. In conclusion we can affirm that the use of CPA in a dosage of 2 mg per day does not lead to serious side effects under long-term follow-up observation conditions and that it's use does not correlate with a higher appearance of liver cell carcinomas.

Uterine leiomyomata and sterility: therapy with gonadotropin-releasing hormone agonists and leiomyomectomy.

The aim of this study was to obtain data about the pregnancy rate in patients with uterine leiomyomata after treatment with gonadotropin-releasing hormone (GnRH) agonists followed by myomectomy. Between 1987 and 1993, 61 patients with uterine leiomyomata and sterility underwent 6 months' GnRH agonist treatment, in part with a surgical intervention. Sixty-two per cent of the patients suffered from concomitant endometriosis. After hormonal therapy 41 patients underwent a myomectomy. According to sonographic and clinical criteria, there was no indication for the enucleation of the leiomyomata for the remaining 20 patients. Owing to the combined therapy, consisting of primary treatment of uterine leiomyomata with GnRH agonists, followed by surgical intervention, 25 patients (41%) suffering from long-term sterility (average 4 years) became pregnant. An early abortion occurred in only three cases (12%). No patient who underwent a myomectomy developed new myomata during the following pregnancy. Four patients suffering from a single leiomyoma became pregnant within the first 3 months after myomectomy, all of them conceiving spontaneously. Considering the high rate of spontaneous conceptions and the low abortion and complication rates during pregnancy, the combined therapy of GnRH agonists followed by myomectomy represents a major step forwards in the effective treatment of sterility in patients with uterine leiomyomata.

[Danazol for treatment of fibrocystic mastopathy]. / Danazol für die Behandlung der fibrozystischen Mastopathie.

59 patients with extensive mastopathia, aged between 23 and 58 years, had been examined over a period of approximately 36 months. They were treated with danazol (Winobanin, Sanofi-Winthrop, Munich) at doses between 100 and 800 mg/day because of an extensive and partly persisting mastopathia. The documented period of treatment ranged between 40 and 774 days. According to the chosen medium daily dose the patients were divided into three groups (< 400 mg/d, 400-600 mg/d, > 600 mg/d). These groups were then subdivided according to criteria of symptoms, palpation findings, mammography and sonography. Between the onset and the end of treatment there was a significant improvement of mastopathia up to a complete recovery in more than 60% of the women. There were no significant systematic differences between the various dosages of danazol. In this respect it was impossible to verify assumed relation between dosage and success of treatment according to anamnestic or demographic factors. The objective evaluation by mammography and ultrasound showed an improvement in 81.4% of the patients, demonstrated by a decreased density of parenchyma and an increased subcutaneous fatty tissue of the mammae. The subjective success of therapy of the patients concerned was judged to be good in 75% of the cases by the doctor and in more than 63% by the patient herself. In conclusion, this study confirms that danazol offers very good therapeutic results for the treatment of the frequently persisting benign breast disease.

[Ovarian suppression with Diane 35/50]. / Die ovarielle Suppression unter Diane 35/50.

In this study, hormone profiles were studied using Diane 35 and Diane 50 before and after treatment for 4-25 months. A comparison of the hormone profiles with Diane 35 or Diane 50 should investigate, if both preparations induce complete ovarian suppression, independent of the given dose of ethinyl oestradiol. 43 patients were treated with Diane 35 and 15 women with Diane 50 over a different lengths of time--up to a period of 25 cycles. Parallel to the determination of the hormone profiles (luteinising hormone [LH], follicle stimulating hormone [FSH], prolactin, oestrone [E1], oestradiol [E2], progesterone, total testosterone [T. T.], free testosterone [F. T.], dehydroepiandrosterone-sulfate [DHEA-S], delta-4-androstenedione [A.] and sex hormone binding globulin [SHBG]), observations on the androgen symptoms before treatment and their course during therapy were made. Moreover, the ratios of LH/FSH and E1/E2 as well as the androgenic index, the ratio of total testosterone/SHBG were determined as control of treatment effects. The most important hormonal changes, which had been observed during a period up to two years are the following: --LH and FSH suppression--prolactin with increasing tendency--decrease of the total androgens and free testosterone-- decrease of the oestrogens E1, E2--increase of SHBG. The confirmation of the efficacy of the anti-androgen/oestrogen combination was reflected by the decline of the androgenic index in all groups. Acne and seborrhoe improved after 3-4 cycles; alopecia after 8-9 cycles and hirsutism diminished after 3 cycles of treatment. In spite of different doses of the combined preparations with 2 mg cyproteronacetate and 0.035 or 0.050 mg ethinyloestradiol, no difference in ovarian suppression as well clinical effects could be found.

[Atypical cytologic findings in pregnancy]. / Atypische zytologische Befunde in der Schwangerschaft.

The clinical significance of dysplasia and precancerous lesions of the cervix in pregnancy, frequency, age distribution and etiological factors is demonstrated based upon the clinical material of the Department of Obstetrics and Gynaecology of the University of Tübingen from 1970 to 1984. The diagnostic and therapeutic guidelines (cytology, colposcopy, histology by biopsy, conisation or hysterectomy) during pregnancy and associated problems are presented in detail. From a total of 168 patients included in the study, 128 revealed the histological classification Pap III/IIID, 38 Pap IVa/b and 2 cases Pap V. Histological carcinoma in situ was verified in 16 cases, microinvasive carcinoma in 6 cases and in 4 cases invasive cancer. From the data obtained, the following conclusions can be drawn: 1. Many of the dysplastic lesions of the cervix in pregnancy are found accidentally because of the limited participation of the patients in the routine cancer screening programme. 2. The precancerous lesions, even unfavourable stages, increase markedly in pregnancy. There is a shift towards younger women. 3. The known risk factors for cervical pre-invasive and invasive cervical abnormalities are confirmed. 4. For the management of cervical dysplasia in pregnancy it could be concluded, that observation by cytology and colposcopy should be done in cases with Pap III/IIID. In cases with Pap IVa/b, careful observation is mandatory, also by biopsy. Doubtful findings require conisation. Generally, this is also possible in pregnancy without complications. If invasion is excluded, an observant attitude may be adopted until delivery.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of bacterial vaginitis. Multicenter, randomized, open study with tinidazole in comparison with metronidazole]. / Behandlung der bakteriellen Vaginose. Multizentrische, randomisierte, offene Studie mit Tinidazol im Vergleich zu Metronidazol.

Seventy-five patients, aged between 18 and 55, with clinical bacterial vaginosis were assigned to two treatments in a randomized fashion. One group received a single oral dose of 2 g tinidazole, the other 2 x 1 vaginal tablet of metronidazole 400 mg on five consecutive days. The clinical success rate (healing and improvement) was 97% in the group treated with tinidazole, and 84% in the group treated with metronidazole. One patient of the tinidazole group and six patients of the metronidazole group had to be given further treatment because of an inadequate response to therapy. Although there were no statistically significant differences between the two groups with respect to clinical effect and tolerance, the results do show that, for the treatment of bacterial vaginosis, a single dose of tinidazole represents a clinically effective and well-tolerated therapy that is minimally stressful for the patient and is particularly suitable for prescription by the practicing physician.

Diagnosis of prospective malignancy in koilocytic dysplasias of the cervix with DNA cytometry.

DNA cytometric measurements were performed with a TV image analysis system on 90 routine cytologic cervical smears from 18 women after automatic restaining of the smears with the Feulgen method. In the cytologic follow-up all the patients revealed borderline lesions (mild to moderate dysplasia) of the epithelium with koilocytosis. Since DNA aneuploidy is widely accepted as a marker for malignancy, an attempt was made to obtain a DNA diagnosis of prospective malignancy in these cases on the basis of the detection of single aneuploid cells. Because koilocytosis strongly suggests human papillomavirus infection, euploid polyploidy might result in up to 8c (c = haploid amount of DNA). Therefore, the aneuploidy detection threshold was set to 9c, excluding values around 16c and 32c (+/- 12.5%) to avoid false-positive diagnoses in cases of higher polyploidy values. The DNA diagnosis of malignancy was made in 13 patients. In 12 of them, carcinoma in situ was diagnosed in the histologic follow-up, resulting in 100% sensitivity of the DNA diagnosis. In five patients no cells greater than 9c were measured, leading to a benign DNA diagnosis. In the histologic follow-up, six patients revealed normal epithelium or moderate dysplasia. Thus, the specificity of the DNA diagnosis was 83.3%.