[Clinical experience with danazol treatment of endometriosis and mastopathy]. / Klinische Erfahrungen mit Danazoltherapie bei Endometriose und Mastopathie.

26 women presenting with internal and external endometriosis and 27 women with chronic cystic mastopathy and mastodyny received 400 mg danazol-a 17-ethinyltestosterone derivate-daily for 3 to 6 months. Before, during and after completion of treatment clinical and endocrinological investigation as well haematological examinations and determinations of blood and urinary chemistry were carried out. In cases of mastopathy plate thermography and mammography were performed; in endometriosis the diagnosis was verified by laparoscopy or-tomy. An improvement in, or disappearance of dysmenorrhoea and pelvic pain was observed in the endometriosis group. At laparoscopy or -tomy a decrease in, but not a complete disappearance of endometriotic foci was seen. A most favourable effect of danazol was seen in mastodyny. A change in plate thermographic or mammographic findings was observed on only a few patients. A significant fall in 17 beta-oestradiol after one month and a slight decrease in basal LH levels (statistical trend) were observed. FSH and HPRL levels were not significantly affected. Ovulation was mostly suppressed, but serum progesterone values were found several times to be in the range characteristic of severe luteal insufficiency (100 to 1500 pg/ml). Hence, not only amenorrhoea, but also breakthrough bleeding occurred. The observed side affects can be ascribed to anabolic (weight gain), androgenic (acne, hirsutism) and hypoestronic (atrophic vaginitis, hot flushes, restlessness) symptomatology.

[The place of laparoscopy in the investigation of infertility (author's transl)]. / Zur Wertigkeit der Laparoskopie in der Sterilitätsdiagnostik.

An assessment of the value of hysterosalpingography (HSG) and laparoscopy was made on the basis of a comparison of the respective findings obtained during routine investigation of 105 women attending the Infertility Clinic. The results of the two procedures concurred in 76% of the women; in the remaining cases, apparently normal findings on HSG had to be rectified on the basis of laparoscopic investigation and vice versa. The divergent results are discussed in detail. In particular, intramural obstruction of the tubes diagnosed on HSG often appears to be merely functional and the presence or absence of adhesions in the region of the tubes must be viewed with reservation. HSG and laparoscopy should be considered complementary, not rival procedures.

[The efficacy of gestoden (delta 15-d-norgestrel) as ovulation inhibitor (author's transl)]. / Zur Ovulatioshemmpotenz von Gestoden (delta 15-d-norgestrel).

Two single-phase combined low-dosage oral contraceptive preparations were tested with respect to their effects on functional parameters of the menstrual cycle. Twenty young women with a normal biphasic menstrual cycle took part in this random study. Evaluation of cervical function, consistency and crystallisation ability of the cervical mucous and of the karyopyknosis index as well as radioimmunoassay of the serum levels of LH, FSH, HPRL, 17-beta-oestradiol and progesterone were carried out consecutively as from the 8th day over the duration of one control cycle and one in which contraceptive as administered. Preparation I (SH D 356 A) contained 75 micrograms delta 15-d-norgestrel (Gestoden) + 30 micrograms ethinyloestradiol. Whilst preparation II (SH D 356 B) contained 75 micrograms d-norgestrel + 30 micrograms ethinyloestradiol. Both substances successfully inhibited ovulation, whereby the former achieved a markedly greater suppression of function with regard to all parameters and, yet good menstrual cycle control was maintained. Hence, gestoden enables the content of active components in oral contraceptives to be reduced even further without detracting from the safety of the technique.

PIP: 2 single-phase combined low dose oral contraceptives (OCs) were tested with respect to their effects on functional parameters of the menstrual cycle. 20 young women with a normal biphasic menstrual cycle took part in this randomized study. Evaluation of cervical function, consistency, and crystallization ability of the cervical mucus and of the karyopyknosis index, as well as radioimmunoassay of the serum levels of LH, FSH, HPRL, 17beta-estradiol, and progesterone were carried out consecutively as from the 8th day over the duration of 1 control cycle and 1 in which OCs were administered. Preparation 1 (SH D 356 A) contained 75 mcg delta 5-d-norgestrel (Gestoden)+30 mcg ethinyl estradiol. Preparation 2 (SH D 356B) contained 75 mcg d-norgestrel+30 mcg ethinyl estradiol. Both substances successfully inhibited ovulation, whereby the former achieved a markedly greater suppression of function with regard to all parameters and, yet good menstrual cycle control was maintained. Hence, Gestoden enables the content of active components in OCs to be reduced even further without detracting from the safety of the method. (author's)

[Central and peripheral actions of an oral contraceptive with reduced oestrogen content (author's transl)]. / Zentrale und periphere Auswirkungen eines Ostrogen-dosisreduzierten oralen Kontrazeptivums

The action spectrum of an oral contraceptive which contained a reduced amount of the oestrogen component (0.04 mg ethinyl-oestradiol and 2.0 mg lynoestrenol) was investigated in 4 volunteer subjects. Serum levels of LH, 17 beta-oestradiol and progesterone were determined by radioimmunoassay and, in addition, the karyopyknotic index and cervical function were studied daily from the 8th day of the cycle. These parameters were determined in a control cycle, in the cycle during administration of the oral contraceptive and in the subsequent treatment-free cycle. Furthermore, the bleeding patterns were studied in 284 treatment cycles of 26 patients. Results of these studies indicate complete contraceptive protection by inhibition of ovulation and by an efficient cervical barrier action already during the first treatment cycle. Withdrawal bleeding was observed 3 to 4 days after ingestion of the last tablet. Spotting was recorded in 11 subjects during the first treatment cycle but was rarely observed during further treatment. Blood loss and bleeding control is comparable to that of other combined oral contraceptives with reduced oestrogen content.

PIP: The action spectrum of an oral contraceptive which contained a reduced amount of the estrogen component (.04 ethinyl estradil and 2 mg lynestrenol) was investigated in 4 volunteer subjects. Serum levels of luteinizing hormone were determined by radioimmunoassay and, in addition, the karyopyknotic index and cervical function were studied daily from the 8th day of the cycle. These parameters were determined in a control cycle, in the cycle during administration of the oral contraceptive, and in the subsequent treatment-free cycle. Furthermore, the bleeding patterns were studied daily in 284 treatment cycles of 26 patients. Results of these studies indicate complete contraceptive protection by inhibition of ovulation and by an efficient cervical barrier action even during the 1st cycle of treatment. Withdrawal bleeding was observed 3-4 days after ingestion of the last tablet. Spotting was recorded in 11 subjects during the 1st treatment cycle, but was rarely observed during further treatment. Blood loss and bleeding control is comparable to that of other combined oral contraceptives with reduced estrogen content.

[The incidence of congenital abnormalities following gestagen administration in early pregnancy (author's transl)]. / Zur Frage der Fehlbildungsraten nach Gestagenmedikation in der Frühschwangerschaft.

198 women who had been trying for years to have a baby were submitted to a trial of prophylactic allyloestrenol therapy in an attempt to lower the incidence of spontaneous abortion. Allyloestrenol (Gestanon) was given at a dosage of 10 mg daily until the 8th week of pregnancy; the dosage was then stepped up to 15 to 20 mg daily until the 12th week of pregnancy and then rapidly tailed off. A decrease in the miscarriage rate was seen only in the group of women in whom treatment had been commenced immediately following ovulation (27 women: 1 miscarriage). If therapy was initiated only after the first missed period then it was without effect (161 women: 23 miscarriages). There were 4 cases of severe congenital abnormality; 3 of these cases arose in the group given allyloestrenol immediately after ovulation (with a drastic reduction in miscarriage rate). The results are discussed. They speak against a cytotoxic effect of the gestagen. It appears likely that the lowering in miscarriage rate occurs at the expense of a failure to prevent the nidation of abnormal fetuses who would normally be aborted.

[Intrauterine contraception with copper-T 200 device- a retrospective analysis of 334 cases (author's transl)]. / Intrauterine Kontrazeption mit dem Kupfer-T-200-Pessar - eine retrospektive Analyse an Hand von 334 einlagen.

A review is given of the findings obtained in 334 women in whom a Cu-T 200 intrauterine device had been inserted at least two years previously and regular follow-up examinations were subsequently undertaken. The most frequent indications were an expressed preference for IUD on the patient's part (38.3%), poor tolerance to the "pill" (24.8%) and so-called "pill fatigue" (11.1%). Varicose veins led to IUD preference in 8.1% and thromboembolic disease in 6.-%. The failure rate - with 12 pregnancies - was 3.6%, all within 6 months of insertion of the device. Half of the pregnancies went to full term and resulted in the birth of mature, healthy babies. The most frequent complication were menstrual disturbances (20.1%). pain (19.5%), cervicitis (18.3%), and adnexitis (13.8%), necessitating removal of the device in 5.7%, 4.2%, 5.1%, and 0.6% of all cases for the afore-mentioned reasons, respectively. These rates are relatively high. The expulsion rate of 2.7% was relatively low, however. Further analysis of the complications led to the observation that menorrhagia was relatively common in nulliparae and in women with retroversion of the uterus, whereas the pre-insertion finding of a pressure-sensitive uterus with a normal ESR, led in a significantly higher percentage of cases to pain and adnexitis. The diagnosis by vaginal probe of a reduced uterine length led to faulty positioning and an increased tendency to pain in a significantly higher number of cases. The fact that only 56.6% of all women tolerated intrauterine contraception well and remained totally symptom-free supports th view held by us that even today the "pill" remains the contraceptive of choice and should be recommended as such.

PIP: A review is given of the findings obtained in 334 women in whom an IUD had been inserted at least 2 years previously. Regular follow-up examinations were subsequently undertaken. The most frequent indications were an expressed preference for an IUD on the part of the patient (38.3%), poor tolerance of the pill (24.8%), and pill fatigue (11.1%). Varicose veins led to IUD preference in 8.1% and thromboembolic disease in 6.0%. The failure rate, 12 pregnancies, was 3.6%, all within 6 months of device insertion. 1/2 of the pregnancies went to term and resulted in the birth of mature, healthy babies. The most frequent complications were menstrual disturbances (20.1%), pain (19.5%), cervicitis (18.3%), and adnexitis (13.8%), necessitating removal of the device in 5.7%, 4.2%, 5.1%, and 0.6% of all cases respectively. These rates are relatively high. The expulsion rate of 2.7% was relatively low. Further analysis of the complications led to the observation that menorrhagia was relatively common in nulliparae in women with a retroversion of the uterus, whereas the preinsertion finding of a pressure-sensitive uterus with a normal ESR, led in a significantly higher percentage of cases, to pain and adnexitis. The diagnosis by vaginal probe of a reduced uterine length led to faulty positioning and an increased tendency to pain in a significantly higher number of cases. The fact that only 56.6% of all women tolerated IUDs well and remained totally symptom-free, supports the view held by us that even today the pill remains the contraceptive of choice and should be recommended as such. (author's)

[Clinical experiences with the prolactin-inhibiting serotonin antagonist metergoline]. / Klinische Erfahrungen mit dem prolaktininhibierenden Serotoninantagonisten Metergolin.

20 puerperal women who did not wish to breast feed their infants were treated with the serotonin antagonist metergoline. In 19 cases effective suppression of puerperal lactation was achieved by the administration of metergoline without the side effects or signs of intolerance. Of 9 women with hyperprolactinaemic amenorrhoea treated with metergoline the raised prolactin level was lowered, followed by menstruation in 7 patients. Ovulation even occurred in 5 of these women. One patient had to discontinue therapy due to intolerance. in normoprolactinaemic amenorrhoea regular menstruation reappeared in 4 out of 5 women; 2 patients even ovulated.

[Hormonal and functional parameters in hyperprolactinaemia (author's transl)]. / Hormon- und Funktionsprofile bei Hyperprolaktinämie.

58 women with raised serum prolactin levels and normal hypophyseal X-ray parameters were subdivided into three groups according to the serum prolactin level (16 to 40, 41 to 80, greater than 80 ng/ml). In addition to the determination of LH, FSH, oestradiol, progesterone and testosterone in the serum and thyroid diagnostic procedures the following hormonal tests were performed: 1. response to gestagen; 2. response to clomiphene; 3. Gn-RH-test for hypophyseal function; 4. ovarian response to administered gonadotropins (only in cases with prolactin levels administered gonadotropins (only in cases with prolactin levels greater than 80 ng/ml). The grade of menstrual cycle disorders depends on the severity of the observed hyperprolactinaemia. Slight disorders like luteal phase insufficiency, anovulatory cycle and oligomenorrhoea are associated with low- or medium-grade hyperprolactinaemia. Mainly secondary, but also primary amenorrhoea is found in cases with higher serum prolactin levels (greater than 80 ng/ml). In these cases the hypophyseal response to Gn-RH is frequently found (61%) to be negative and, moreover, the ovarian response to administered gonadotropins seems to be diminished. Increasing HPRL levels often appear to be associated with a negative response to the other above-mentioned tests.

[Treatment of infertile couples--an interdisciplinary task (author's transl)]. / Behandlung der sterilen Ehe--Eine interdisziplinäre Aufgabe.

The results obtained by closest cooperation between gynaecologist and andrologist in the treatment of sterile marriages are reported. 127 couples were treated over a period of 20 months. Almost 100% of the males and 60% of the females were sub- or infertile. Treatment of both partners was meticulously coordinated in order to increase the success ratio. Interdisciplinary cooperation seemed to be advantageous particularly in homologous insemination. 23 pregnancies were achieved, i.e. 18.1%, despite the unpromising nature of this negatively selected material.

[Hypophyseal reaction state during oral contraceptiva (author's transl)]. / Die hypophysäre Reaktionslage unter oralen Kontrazeptiva.

In 5 normocyclic women, firstly taking a conventional oral contraceptive, Neogynon (50 mcg EE + 250 mcg levo-norgestrel) for 6 months, the levels of LH, 17 beta-E2 and progesterone did not rise after changeover to a dose-reduced pill, Microgynon 30 (30 mcg EE + 150 mcg levo-norgestrel). This fact indicates maintained central suppression. Examination of the hypothalamic-hypophyseal axis by the Gn-RH test (50 mcg) with Microgynon 30 showed negative results during the first treatment cycle in 13 out of 18 women. In the 6th treatment cycle only 7 Gn-RH non-reactive women were observed and after stimulation with 100 mcg Gn-RH only 5 women remained with negative Gn-RH tests. Of the 20 women who took conventional oral contraceptives over a period of 6 months to 6 years (7 took Eugynon: 50 mcg EE + 500 mcg D,L-norgestrel, 5 Lyndiol: 75 mcg mestranol + 2.5 mg lynoestrenol, 8 Neogynon, only one from the Neogynon group showed a positive result. On the other hand there was a positive reaction in 4 out of 7 women using the two step dose-reduced preparation Sequilar (11 tablets of 50 mcg EE + 50 mct levo-norgestrel and 10 tablets of 50 mcg EE + 125 mcg levo-norgestrel).

PIP: In 5 normocyclic women taking the oral contraceptive (OC) Neogynon (50 mcg ethinyl estradiol [EE] + 250 mcg levonorgestrel), the levels of LH, 17beta-estradiol 2, and progesterone did not rise after changeover to a dose-reduced pill Microgynon 30 (30 mcg EE + 150 mcg levonorgestrel). This fact indicates maintained central suppression. Examination of the hypothalamic-hypophyseal axis by the Gn-RH test (50 mcg) with Microgynon 30 showed negative results during the 1st treatment cycle in 13 of 18 women. In the 6th treatment cycle, only 7 Gn-RH nonreactive women were observed, and after stimulation with 100 mcg Gn-RH, only 5 women remained with negative Gn-RH tests. Of the 20 women who took conventional OCs over a period of 6 months-6 years (7 took Eugynon--50 mcg EE + 500 mcg D'L norgestrel; 5 Lyndiol--75 mcg mestranol + 2.5 mg lynestrenol; 8 Neogynon). Only 1 from the Neogynon showed a positive result. On the other hand, there was a positive reaction in 4 of 7 women using the 2-step dose-reduced preparation Sequilar (11 tablets of 50 mcg EE + 50 mcg levonorgestrel and 10 tablets of 50 mcg EE + 125 mcg levonorgestrel. Our results suggest that preparations with reduced steroid content influence hypophyseal function to a lesser extent, while simultaneously maintaining hypothalamic suppression, than conventional combinations of steroids do. (author's)

[Timing of ovulation in clomiphene-induced cycles (author's transl)]. / Zur Diagnostik des Ovulationszeitpunktes in clomipheninduzierten zyklen.

214 menstrual cycles, induced by clomiphene in 121 women desiring a family but manifesting disturbances of cycle, type WHO II (1976) were investigated with regard to pattern of cervical function. 184 were ovulatory cycles. The time of ovulation was predictable within a range of two days in 58.7% of cases by means of the cervical score, consisting of the dilatation of the cervical os, the degree of transparency, the quantity and the consistency of the cervical mucus. The occurence of the "LH peak" and the rise in basal body temperature (BBT) were set in relation to this. In 41.3% of cycles the cervical score, influenced by the antioestrogenic effect of clomiphene, gave only insufficient evidence. In subsequent treatment cycles the cervical function, in relation to the individual case and the inducible quality of the cycle, showed a similar response rate as in the first treatment cycle. Our results suggest that, after examination of the first clomiphene-induced cycle by the combined means of cervical score and hormoneanalytic methods, patients with a positive cervical response, can be investigated by any interested doctor, even if he doesn't have a laboratory at his disposal, in order to assess the timing of ovulation for therapeutic measures.

[Hormonal and functional parameters in hyperprolactinaemia (author's transl)]. / Hormon- und Funktionsprofile bei Hyperprolaktinämie.

58 women with raised serum prolactin levels and normal hypophyseal-X-ray parameters were subdivided into three groups according to the serum prolactin level (16 to 40, 41 to 80, greater than 80 ng/ml). In addition to the determination of LH, FSH, oestradiol, progesterone and testosterone in the serum and thyroid diagnostic procedures the following hormonal tests were performed: 1. response to gestagen; 2. response to clomiphene; 3. Gn-RH-test for hypophyseal function; 4. ovarian response to administered gonadotropins (only in cases with prolactin levels greater than 80 ng/ml). The grade of menstrual cycle disorders depends on the severity of the observed hyperprolactinaemia. Slight disorders like luteal phase insufficiency, anovulatory cycle and oligomenorrhoea are associated with low- or medium-grade hyperprolactinaemia. Mainly secondary, but also primary amenorrhoea is found in cases with higher serum prolactin levels (greater than 80 ng/ml). In these cases the hypophyseal response to Gn-RH is frequently found (61%) to be negative and, moreover, the ovarian response to administered gonadotropins seems to be diminished. Increasing HPRL levels often appear to be associated with a negative response to the other above-mentioned tests.

[Anti-androgen treatment of acne (author's transl)]. / Die Anwendung von Antiandrogenen in der Behandlung der Akne.

A group of women suffering from acne vulgaris or post-pubertal acne was selected for a trial of anti-androgen treatment on the basis of suspected concomitant endocrine disorder from the case history. A satisfactory response to anti-androgen treatment was obtained in 80% of these subjects. The serum testosterone levels, which were slightly elevated or within the normal range prior to therapy, decreased significantly in response to anti-androgen treatment with an oral contraceptive of the combined type containing cyproterone acetate and ethinyl oestradiol. The highest rate of response was observed in patients with post-pubertal acne resistant to conventional therapy.

[Results of a long-term clomiphene citrate therapy in women with normogonadotropic menstrual disturbanes (author's transl)]. / Ergebnisse einer Langzeitbehandlung mit Clomiphenzitrat bei Frauen mit normogonadotropen Zyklusstörungen.

A total of 72 pregnancies was achieved in 59 women with menstrual cycle disturbances (WHO Type II) by administration of clomiphene. 27 of these pregnancies (34.7%) occurred only after more than three courses of cloimphene. A secondary classification of the patients was based on the symptomatic severity of the menstrual disturbance. Clomiphene (100 mg) was administered on the fifth day after the onset of menstruation for five days, whereby in one or two cases up to 19 courses had to be given. The group consisted of women who had rejected HMG-HCG therapy because of the possibility of multiple pregnancy. 59 pregnancies went to full term; 2 tubal pregnancies and 11 cases of miscarriage were recorded. The commencement of pregnancy was evaluated and the time of ovulation and the length of the luteal phase determined in women requiring up to three courses of clomiphene and those requiring over three courses. The investigation demonstrates that clomiphene therapy can be successful even after more than six courses of the drug. Side effects are minimal.

[Changes in glucose tolerance, serum insulin and blood lipids during contraceptive medication (oestrogen-gestagen) in metabolically-healthy women (author's transl)]. / Glukosetoleranz, Insulin und Blutlipide unter einem Ovulationshemmer bei stoffwechselgesunder Frauen

A low-dosage combination type of contraceptive (oestrogen-gestagen) was given to 19 metabolically- healthy women of normal weight over a period of 6 months. Glucose tolerance, serum insulin and serum lipids were measured 1 month before, during and 2 months after medication. There was a slight decrease in the basal insulin values and an opposite trend in the basal blood glucose values, not exceeding 10 mg% in comparison to pretreatment values. The oral glucose tolerance test with a load of 100 g oligosaccharides did not show any statiscally significant changes during the 9 month observation period. The serum insulin curve, however, showed a delayed increase with a tendency to return to original values after medication had stopped. A slight degree of insulin resistance without change in glucose tolerance can, therefore, be assumed. There was a tendency for triglyceride values to increase over the observation period. A trend towards decreased cholesterol, on the other hand, was statistically insignificant. The observed changes were all within the normal range in all cases.

[Prophylactic medication to prevent miscarriage in pregnant women with a history of sterility (author's transl)]. / Zur Frage einer prophylaktischen Schwangerschaftsschutzmedikation bei Frauen mit erfolgreich behandelter Sterilität.

A report is given of the outcome of 451 pregnancies occurring among women who had previously attended the Infertility Clinic. General gestagen therapy was given prophylactically in 129 cases before the appearance of any signs of threatened abortion. Massive gestagen therapy was initiated in 41 cases in response to signs of threatened abortion. Gestagen was not given either prophylactically or therapeutically in the remaining 281 pregnancies. The incidence of abortion was 10.1% in women given prophylactic gestagen, whilst the overall rate of abortion in the entire series of 451 women was 13.3%. It transpired on closer scrutiny of the 129 cases given prophylactic gestagen therapy that the abortion rate was 12.0% in the 108 pregnancies in which prophylactic gestagen therapy had been initiated at the time of the first missed period or later, whereas not one single abortion was registered amongst the 21 women who had been given gestagen therapy in the immediate post-ovulatory phase. It can be concluded that commencement of prophylactic gestagen therapy at the earliest possible moment provides optimum conditions for successful implantation of the fertilized ovum, especially in cases with masked insufficiency of the corpus luteum.