International Journal of Gynecology & ObstetricsVolume 107, Issue S2 p. S72-S72 Invited presentations I290 Progesterone and progestins in pregnancy: Clinical relevance for treatment and prevention A.E. Schindler, A.E. SchindlerSearch for more papers by this author A.E. Schindler, A.E. SchindlerSearch for more papers by this author First published: 20 November 2009 https://doi.org/10.1016/S0020-7292(09)60290-3AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume107, IssueS2Abstracts of XIX FIGO World Congress of Gynecology and ObstetricsOctober 2009Pages S72-S72 RelatedInformation

From October 1985 to November 1987, arterial regional chemotherapy with mitoxantrone was undertaken in 18 patients with primary far advanced carcinoma of the breast, of inflammatory or ulcerating type. Two patients had a bilateral carcinoma. Eight weeks after regional chemotherapy 18 of 20 tumours had become operable. Regression of tumour size by at least 50% (checked by mammography) was achieved in seven patients. Axillary lymphadenectomy gave negative results in 6 of 17 patients. Conversion of the receptor status occurred in only 2 of 12 patients. There were only few side effects: alopecia in 20%, leucopenia less than 2,500/microliters in 18%, thrombocytopenia less than 100,000/microliters in 7% patient. After a follow-up period of up to 28 months local recurrence was noted in two, distant metastases in three cases. A totally disease-free period was achieved in 14 patients.

INTRODUCTION:Antibiotic prophylaxis is a standard procedure in obstetric surgery and has been discussed in various investigations. Use of treatment is judged by high efficacy and good tolerance.METHOD:In 300 patients undergoing cesarean sections we compared results of application of Piperacillin 4 g and Piperacillin/Tazobactam 4.5 g after cut of umbilical cord. Tazobactam/Piperacillin is a combination of a broad-spectrum penicillin and a beta-lactamase inhibitor with increased toxicity against staph. aureus, enterobacter, and other germs responsible for local and systemic infections in obstetric surgery.RESULTS:We did not observe any severe adverse effects. Rate of severe wound infections was 1.3 % (Tazobactam/Piperacillin) and 2 % (Piperacillin alone). The difference showed no statistic significance (p > 0.01). During postoperative course we found a higher increase of CRP (p < 0.01) in the Piperacillin group. CRP proved to be a useful objective parameter to distinguish between patients with or without postoperative infections. No differences were found in the number of leucocytes, time in hospital and other parameters.

High-dose dienogest (20 mg/day) was used for the treatment of endometriosis in women aged 18-52 years after laparoscopic and histological diagnosis of endometriosis and staging according to the revised American Fertility Society criteria. Treatment efficacy was analyzed objectively by second-look laparoscopy, and serum hormone measurements and evaluation of endometriosis-related symptoms were performed done and side-effects recorded. Compared with other high-dose progestin therapies, treatment with dienogest was shown to be effective even in stage IV endometriosis. The side-effect profile of the high-dose dienogest treatment appears to be highly favorable compared with other treatments. Neither the menopausal symptoms caused by therapy with gonadotropin-releasing hormone agonists nor the adverse androgen-related effects induced by danazol were observed. Therefore, long-term high-dose dienogest therapy can be recommended particularly for women with progressive endometriosis.

Available data indicate that progesterone is able to treat pregnancy-induced hypertension (preeclampsia). Dydrogesterone and 17alpha-hydroxyprogesterone caproate might also be used for this purpose. Prevention of hypertensive disorders in preeclampsia also seems possible, but studies are needed to confirm this.

Premature birth represents a major cause of perinatal morbidity and mortality. The short- and long-term sequelae of prematurity have serious consequences for newborn survival and health in later life. In addition, prematurity is a major problem with regard to health expenditure. Despite major progress in obstetrics, perinatology and neonatology, the percentage of premature birth persists and there is even a tendency towards a slight increase. Therefore, besides screening programmes for the detection of vaginal infections, additional therapeutic opportunities must be sought. According to previously published data, vaginal progesterone and intramuscular 17alpha-hydroxyprogesterone caproate should be considered possible treatment options for the prevention of preterm delivery.

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The purpose of this study was to provide a diagnostic and a prognostic variable that could easily be measured in the laboratory, and that would predict the need for future therapy of persistent gestational trophoblastic disease. There would no longer be a need to treat all cases of hydatidiform mole prophylactically, to improve the outcome in only about 20% predicted to develop malignant gestational trophoblastic tumors. Circulating β-human chorionic gonadotropin (β-hCG), progesterone, 17β-estradiol and inhibin levels were measured using standard radioimmunoassays in 60 patients with complete hydatidiform mole and in 20 normal pregnant women of a corresponding duration of pregnancy and having a maternal indication for therapeutic abortion. There were no significant statistical differences between the two groups as regards gravidity, parity and gestational age. There was a significant statistical difference between patients with a molar pregnancy who developed gestational trophoblastic tumors (GTT) and those who did not develop GTT as regards pre-evacuation and follow-up mean serum β-hCG, mean serum progesterone and mean serum 17β- estradiol levels. These findings together with the persistently elevated mean serum progesterone and mean serum 17β-estradiol levels at 6 weeks after evacuation in all cases who developed GTT suggested that progesterone as well as 17β-estradiol serum levels might be of prognostic value in cases of molar pregnancy. However, larger numbers of cases are required to correlate findings to β-hCG serum level. Although mean serum inhibin level was significantly higher in women with hydatidiform mole than in normal pregnant women, it lacks any prognostic value for detection of subsequent gestational trophoblastic tumors.

Preterm delivery with its short-term and long-term sequealae constitutes a serious problem in terms of morbidity, disability and mortality of the newborn and cost to the society. The incidence of premature deliveries persists and according to the latest national and international reports a tendency for an increase has been observed. Therefore, besides screening programmes for the detection of vaginal infections one has to look for additional therapeutic concepts. According to previous data and recent publications, progesterone vaginally and 17alpha-hydroxyprogesterone caproate intramuscularely should be considered as possible treatment options for the prevention of preterm delivery in high-risk women, with therapy starting in the second trimester.

Objectives: Uterine lyomyomata are the most common benign tumours during reproductive life. GnRH-agonists have become a useful tool in the management of benign fibroids. The aim of this study was to investigate if treatment with GnRH-agonists is able to modify the proliferation rate and cell biological markers of uterine fibroids and enhance therapy of this benign disease. Patients and methods: Sixty-seven myoma and in 22 cases the corresponding myometrium were investigated in this study. Twenty patients with fibroids underwent a GnRH-agonist treatment for 3–6 months (Enantone®-Gyn) whereas the remaining 20 patients had regular menstrual cyclings or were postmenopausal. The proliferation marker Ki-67 and the differentiation markers desmin, vimentin and M-cadherin and were analyzed. Results: Independent of the hormonal situation at time of biopsy no differences concerning the cell biological differentiation markers between the GnRH-agonist treated group and the not treated group could be observed (p>0.05). GnRH-agonist treatment leads to a significant (p<0.05) reduction of the cell proliferation rate of uterine myoma but not to changes in uterine differentiation. Discussion: GnRH-agonists are potent drugs in the treatment of benign gynaecological diseases. This is one of the first investigations that describe the potency of GnRH-agonist to reduce, statistically significantly, the proliferation rate of uterine myoma. By the same way, it could be demonstrated that GnRH-agonists do not lead to differentiations of smooth muscle cells, so that the use of GnRH-agonists in the treatment of uterine fibroids can be seen as useful for reduction of lyomyomata volume, but it is not able to change significantly differentiation parameters of these benign smooth muscle cell tumours.

To examine the pathogenesis of hyperthyroidism in women with trophoblastic diseases, the biological activity of human chorionic gonadotropin (hCG) molecules in women with normal pregnancy (n = 85) and in women with trophoblastic diseases (vesicular mole, n = 30; and choriocarcinoma, n = 12) was compared. Hyperthyroidism (thyroid stimulating hormone (TSH) < 0.3 mIU/l) was observed more frequently in women with trophoblastic diseases. All the sera were then subjected to Chinese hamster ovary cells transfected with the human TSH receptor (CHO-hTSHr cells) and cAMP production was compared. Sera from the women with choriocarcinoma showed the highest cAMP production. Interestingly, significant correlation between serum hCG level and cAMP production in CHO-hTSHr cells was observed only in women with trophoblastic disease. All the sera were then applied to CHO cells transfected with hCG/luteinizing hormone (LH) receptor (CHO-hCG/LHr cells). In contrast to the findings with the TSH receptor, sera from the women with normal pregnancy showed the highest cAMP production in these cells. Correlation between serum hCG level and cAMP production in CHO-hCG/LHr cells was significant only in normal pregnancy. These results indicate that the hCG molecule from women with trophoblastic diseases displays enhanced thyrotropic activity.

First-trimester endocrinology is determined on the one hand by corpus luteum progesterone and estradiol biosynthesis and secretion and on the other hand by the time of onset and extent of progesterone and estradiol secretion by the placenta. This dual interplay is dominated by the corpus luteum placental shift, where a relative progesterone and estradiol deficiency can develop and may lead to early as well as late abortion. Measurements of serum progesterone and estradiol are mandatory in order to reveal such deficiencies and to treat them effectively with 17 alpha-hydroxyprogesterone caproate in combination with estradiol valerate or with progestins such as dydrogesterone.

Besides the natural progestin, progesterone, there are different classes of progestins, such as retroprogesterone (i.e. dydrogesterone), progesterone derivatives (i.e. medrogestone) 17alpha-hydroxyprogesterone derivatives (i.e. chlormadinone acetate, cyproterone acetate, medroxyprogesterone acetate, megestrol acetate), 19-norprogesterone derivatives (i.e. nomegestrol, promegestone, trimegestone, nesterone), 19-nortestosterone derivatives norethisterone (NET), lynestrenol, levonorgestrel, desogestrel, gestodene, norgestimate, dienogest) and spironolactone derivatives (i.e. drospirenone). Some of the synthetic progestins are prodrugs, which need to be metabolized to become active compounds. Besides the progestogenic effect, which is in common for all progestins, there is a wide range of biological effects, which are different for the various progestins and have to be taken into account, when medical treatment is considered.

METHODS:Circulating CA 125, CA 19-9, CA 15-3 and carcinoembryonic antigen (CEA) levels were studied in sixty patients with hydatidiform mole and in twenty normal pregnant women of a corresponding duration of pregnancy.DISCUSSION:Serum levels of CA 125, CA 15-3 and CEA are not affected by molar pregnancy. The mean level of CA 19-9 in maternal serum is significantly lower in cases of molar pregnancy when compared with cases of normal pregnancy. The amnion cell origin of CA 19-9 could explain the statistically significant difference between cases of therapeutic abortion and cases of HM (complete HM lacks amniotic membrane).

Prolonged exposure to unopposed estrogens has a proliferative effect on the endometrium and can induce endometrial carcinoma. We describe a massively obese postmenopausal woman with high levels of endogenous estrogens who developed proliferative changes in the ovaries and the uterus in addition to endometrial hyperplasia and carcinoma. This case underlines the importance of primary prevention of gynecologic conditions and of the use of progestins in postmenopausal women.

In vitro immunological and biological activity of four commercially available preparations of human chorionic gonadotropin (hCG) for clinical use (Predalon(R): hCG-A, Primogonyl(R): hCG-B, Choragon(R): hCG-C and Pregnisin(R): hCG-D) were examined. The methods used include immunoassay, cAMP production in Chinese hamster ovary (CHO) cells and structural analysis of hCG with high performance liquid chromatography (HPLC). There were remarkable differences in immunological activities among preparations. hCG-D had the highest concentration of free hCGbeta. In CHO cells, production of cAMP with hCG-C was significantly higher than that with other preparations. Analyses in HPLC showed similar pattern in hCG-C and a standard preparation of hCG (CR 123). The highest immunological activity in hCG-A could be attributed to the presence of nicked form of hCG in this preparation. Various hCG components in preparation may explain these differences.