Indications and Route of Hysterectomy for Benign Diseases. Guideline of the DGGG, OEGGG and SGGG (S3 Level, AWMF Registry No. 015/070, April 2015)

Background: Official guideline "indications and methods of hysterectomy" to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.

The Prevention of Positioning Injuries during Gynecologic Operations. Guideline of DGGG (S1-Level, AWMF Registry No. 015/077, February 2015).

Purpose: Official guideline published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). Positioning injuries after lengthy gynecological procedures are rare, but the associated complications can be potentially serious for patients. Moreover, such injuries often lead to claims of malpractice and negligence requiring detailed medical investigation. To date, there are no binding evidence-based recommendations for the prevention of such injuries. Methods: This S1-guideline is the work of an interdisciplinary group of experts from a range of different professions who were commissioned by DGGG to carry out a systematic literature search of positioning injuries. Members of the participating scientific societies develop a consensus in an informal procedure. Afterwards the directorate of the scientific society approves the consensus. The recommendations cover.

Diagnostic approach and therapeutic management in early-stage endometrial cancer.

OBJECTIVE: The effectiveness of pelvic and para-aortic lymphadenectomy in the morbidity of patients affected by early-stage endometrial carcinoma (EC) is the subject of this study. STUDY DESIGN: Ninety-two cases with endometrial cancer that underwent para-aortic and pelvic lymphadenectomy, from June 1995 to June 2006, were studied and compared with 30 cases of patients with endometrial cancer without lymphadenectomy. RESULTS: According to the results, systematic pelvic and para-aortic lymphadenectomies improved disease-free and overall survival rates among the patients with endometrial cancer. The mean number of removed para-aortic lymph nodes was 19.01 +/- 5.88, whereas the mean number of removed iliac lymph nodes was 32.94 +/- 6.69. Forty-two and 31 metastatic iliac and para-aortic nodes were found, respectively. No surgery-related deaths and major intraoperative injuries occurred. The frequency and the type of postoperative complications were not affected by the performance of lymphadenectomy. The morbidity rate was 6.2%, similar to the group without lymphadenectomy (5.79%). No recurrence occurred in the group with lymphadenectomy, while in the other group the recurrence rate was 23.3%. CONCLUSIONS: Lymph nodes metastases can be observed in early stages of EC. Pelvic and para-aortic lymphadenectomies seems to provide profound information about the Stage of the disease and the patient's survival, identifying which patients are suitable for supplementary treatment, without significant clinical increase of morbidity.

A retrospective analysis of twenty-eight borderline ovarian tumours in adolescent girls.

The aim of this retrospective study was to evaluate the clinical reproductive outcome and the rate of recurrence of low malignant ovarian tumors in adolescent girls after conservative surgical treatment by laparoscopy or laparotomy. We report 28 cases of borderline ovarian tumors (BOTs), that were surgically treated from 1990 to 2006 at the Obstetrical and Gynecological Department of Democritus University in Greece and the Aschaffenburg Teaching Hospital in Germany. All patient information was obtained by reviewing hospital records. BOT lesions in teenagers were associated with variable non-specific presenting symptoms. Ultrasonographic investigations can be helpful in the early diagnosis of BOTs in teenage girls. Most of the patients were diagnosed at an early stage. Available data of our study indicate that in these patients, fertility, pregnancy outcome and survival remain excellent.

Laparoscopic treatment of ovarian dermoid cysts.

Dermoid cysts are the most common germ cell tumors of the ovary in women of reproductive age. We report 67 cases of patients with dermoid cysts (mean age, 31.31 years) originating from the ovary treated from 1994 to 2006 at the Obstetrics and Gynecology Department of Aschaffenburg Hospital-Clinic in Germany. Most patients (60) underwent cyst removal. In two patients salpingo-oophorectomy was performed and in five partial oophorectomy was performed. Additional surgery ensuing laparotomy was never necessary. None of the patients had long-term postoperative complications. Two patients were at nine and 15 weeks of gestation and postoperatively were well following termination of pregnancy. In a group of 43 women, who desired pregnancy, 37 pregnancies resulted. The overall intrauterine pregnancy rate was 83.7%; one patient had an ectopic pregnancy (2.32%). To receive more information on this disease, treatment should be performed according to international protocols.

Uterine sarcoma: a report of 57 cases over a 16-year period analysis.

Uterine sarcomas comprese approximately 4-9% of all uterine malignant tumors with a poor prognosis. We report 57 cases of sarcoma originating in the uterus treated from 1990 to 2006 at the Department of Obstetrics and Gynecology of Democritus University of Thrace, Greece and the Department of Obstetrics and Gynecology of Aschaffenburg Hospital, Germany. The median age of occurrence was 49 years with the commonest symptom being abnormal uterine bleeding. Forty-nine patients underwent a total hysterectomy and bilateral salpingo-oophorectomy whereas 17 cases underwent radical lymphadenectomy. During the last followup (December 2006), six patients were alive and well with no evidence of disease, 23 patients had died of undercurrent disease, and 28 were alive with recurrence of disease. These rare cancers can be aggressive, and account for a greatly disproportionate number of deaths from uterine cancers. Treatment for this rare disease should be performed according to international protocols in order to have the most updated information.

Attitudes towards contraception in three different populations.

OBJECTIVE: To investigate contraceptive behavior of women belonging to three different ethnic and/or socioeconomic populations as well as to evaluate the main sources of information concerning contraception in each population. METHODS: 150 Muslim women living in Germany (group A), 120 Muslim women living in Thrace, Greece (group B) and 140 Christian Orthodox women living in Thrace, Greece were enrolled in the study. Attitudes concerning contraceptive practices were assessed by means of a questionnaire. Demographic and socioeconomic characteristics of each group were compared with the method of contraception used. Statistical analysis was performed using one-way analysis of variance (ANOVA), followed by Turkey's test, chi-square test and multiple logistic regression analysis. RESULTS: The contraceptive pill (41.7%), the condom (35.1%), periodic abstinence (24.4%) and interrupted coitus were the most common methods of contraception. The gynecologist (23.4%), the family consultant (12.0%) and the sexual partner (10.2%) were the most usual sources of information. The use of contraceptive pills was more frequent among Muslims from Germany and Christians from Greece (p < 0.001), while the use of condoms was more frequent among Christians from Greece (p = 0.019). The use of IUDs was more frequent among Muslims from Germany and Greece (p = 0.039). CONCLUSIONS: Our study results reveal that there are behavioral differences between race/ethnic groups and minorities regarding contraceptive practices, probably due to different cultural, socioeconomic and educational factors.

Contribution of laparoscopy in young women with abdominal pain.

This study retrospectively evaluates the laparoscopic treatment of acute abdominal pain in 120 young girls aged 13 to 25 years from 1990 to 1995. Seventy-two (60%) of all operations were emergency procedures. Of these, 55 had functional ovarian cysts, eight patients were operated on for adnexal torsion and nine patients had other adnexal conditions. Ovarian cyst resection was performed in 46 patients and ovarian cyst coagulation in 17 patients. In the rest of the 48 patients (40%), 31 (26.67%) cases had pelvic inflammatory disease, three (2.5%) benign ovarian tumors, two (1.6%) ectopic pregnancies, one (0.8%) a paraovarian cyst and 11 (5%) endometriosis. Laparoscopy appeared to be a safe and effective surgical procedure.

Effect of two oral contraceptives containing ethinylestradiol and levonorgestrel on serum and urinary surrogate markers of endothelial function.

OBJECTIVE: To investigate the effect of two oral contraceptives containing 0.02 mg ethinylestradiol and 0.1 mg levonorgestrel (Formulation A, Leios), and the other containing 0.03 mg ethinylestradiol and 0.15 mg levonorgestrel (Formulation B, Stediril 30) on the serum and urinary concentrations of various markers reflecting the status of vascular tone and development of atherosclerosis. The adhesion molecules E-selectin, inter-cellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and homocysteine were included as serum markers and cGMP, prostacyclin and its antagonist thromboxane as urinary markers. METHODS: In a comparative, double-blind, randomized, parallel group study, 34 women received formulation A and 33 women formulation B. Serum samples were collected before treatment and after 3, 6 and 12 cycles. Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles. Serum and urinary markers were measured by enzyme immunoassays. RESULTS: E-selectin levels were significantly reduced by both contraceptives after 3, 6 and 12 months compared to pretreatment levels. A slight increase in ICAM concentrations was observed for both contraceptives after 6 cycles, but this fell to pretreatment levels after 12 cycles. VCAM values were significantly lowered after 3, 6 and 12 months by both contraceptives. No significant changes were found in serum levels of homocysteine. No significant differences were found between treatment groups for the serum markers. Both contraceptives significantly enhanced urinary cGMP excretion after 12 cycles. The prostacyclin metabolite remained unchanged in the case of both formulations, but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to thromboxane, decisive for the resulting effect on vascular tone, increased significantly. CONCLUSION: These results indicate that the low-dose oral contraceptives can reduce the production of adhesion molecules which play a crucial role in the early stages of atherosclerosis. In addition, these contraceptives can shift the balance of vascular tone towards dominance of vasodilatory substances after 12 cycles of treatment. Thus, the positive influence of these contraceptives on the various markers investigated may improve vascular tone and impede development of atherosclerosis.

Effect of sequential estrogen/progestin treatment on biochemical vasoactive markers in postmenopausal women comparing oral and transdermal application.

PURPOSE: Estrogen replacement in postmenopause can elicit vasodilatory effects which may be important for cardiovascular protection. Progestin addition can antagonise this beneficial effect, but until now, only a few studies have been performed on this issue. In the present study the effect of estradiol as well as of added norethisterone acetate (NETA), a C19-progestin, on the renal excretion of various biochemical markers which can reflect vasoactive actions was investigated. METHODS: 37 postmenopausal women were treated for one sequential estrogen/progestin treatment cycle, i.e. two weeks with estradiol alone followed by two weeks with an estradiol/progestin combination. Both oral (n = 20) as well as 'complete' transdermal (n = 17) hormone substitution was applied, and the excretion of the following vasoactive substances or the stable metabolites, respectively, were measured in nocturnal urine prior to treatment, after 14 and 28 days: cGMP, which can reflect the production of nitric oxide, prostacyclin, thromboxane and serotonin. RESULTS: The excretion of cGMP was increased with both forms of administration during the estrogen phase as well as during the consecutive estrogen/progestin treatment. The prostacyclin-thromboxane quotient increased during estrogen phases, but decreased significantly by the addition of oral, but not with transdermal NETA, reflecting possible vasoconstrictory effects. Serotonin excretion increased, but this only was significant after the oral estrogen-only phase (2 weeks treatment), and after one cycle of complete transdermal treatment (4 weeks treatment), respectively. CONCLUSION: The observed effects can be explained by vasodilatory actions during the estrogen phases which can be maintained or even increased during the consecutive estrogen/progestin treatment suggesting a time-dependent beneficial estrogen effect. However, oral progestin addition may antagonise this effect already within two weeks of treatment whereby the prostacyclin-thromboxane quotient seems to be the most sensitive marker surrogating on vasoconstrictory progestin action.

[Complications and results of peri-aortocoval lymphadenectomy in gynecology]. / Komplikationen und Ergebnisse der periaortokavalen Lymphadenektomie in der Gynäkologie.

Periaortocaval lymphadenectomy has a low morbidity and mortality rate. The extent of affiliated procedures like radical hysterectomy and the general risk pattern of the individual patient determines the morbidity and mortality of the whole procedure. The necessary extent of periaortocaval lymphadenectomy can be derived from anatomic autoptic and histologic studies. The resection of 20 +/- 5 lymphatic notes can be achieved safely. This number can be regarded as a quality standard. The diagnostic impact on prognosis and therapy is well established while the therapeutic value of periaortocaval lymphadenectomy remains to be evaluated.

[Rationale for prescribing oral contraceptives]. / Rationale für die Verordnung oraler Kontrazeptiva.

Strategies for prescribing oral contraceptives (OC) are explained with particular emphasis on individual conditions which can be helpful to optimize the selection process out of the numerous on the market. While contraceptive efficacy unequivocally is regarded as high additional non-contraceptive benefits become substantial criteria for an individual decision. Antiandrogenic properties of progestogens like cyproteroneacetate clearly determine their preference in the presence of unwanted clinical signs and symptoms of hyperandrogenism. In most of the non androgen-related conditions the estrogenicity of a preparation as a result of the dose of ethinylestradiol and dose as well as antiestrogenic potency of the progestogen accounts for the majority of non contraceptive effects. Different progestogens are evaluated with respect to their antiestrogenic property. It is suggested to start treatment after selection of an appropriate progestogen with the lowest daily dose of both hormonal components and to continue intake at least for 3 to 4 cycles as long as no serious adverse events occur. In cases of persisting problems i.e. bleeding irregularities doses or dosing-schemes should be altered preferentially without switching to another gestagen.

PIP: It is vital when one is prescribing oral contraceptives to choose antiestrogenic gestagens with antiandrogenic properties if conditions like acne, alopecia, or hirsutism are present. Cyproterone acetate, chlormadinoacetate, and dienogest are the most effective antiandrogens. Sex hormone-binding globulin (SHGB) is the most important parameter for the effect of estrogen on the liver, and its measurement can help determine the total estrogen content of various preparations. The SHGB increase should always be measured after at least 3 cycles of treatment with monophasic combination preparations of different gestagens. The dose of ethinyl estradiol for levonorgestrel (LNG), gestoden, desogestrel, and dienogest, respectively, used to be 30 mcg, and for norgestimate and norethindrone it was 35 mcg; the dose would be assessed to ascertain the antiestrogenic effect of these preparations. LNG is the gestagen with the strongest antiestrogenic effect. This has been qualitatively supported by findings from an investigation with a combination of 20 mcg ethinyl estradiol plus 100 mcg LNG, which showed that no change of the SHGB level occurred after 3 cycles. It is reasonable to choose a preparation with the lowest estrogen and gestagen dose and to change the dosage only after 3-4 months of use at the earliest if side effects such as bleeding irregularities occur. Other options are gestagen monopreparations or an LNG-containing IUD system. For women in the last third of their fertile phase, the use of a gestagen-containing system allows for the balancing of an existing estradiol deficit.

Influence of norethisterone acetate and estradiol on the serotonin metabolism of postmenopausal women.

Previous studies have shown that estradiol increases urinary excretion of the main stable metabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), reflecting an increase in serotonin production. In the present study, the effect of the progestin norethisterone acetate (NETA) on serotonin metabolism was investigated, both alone and in addition to estradiol replacement in 20 postmenopausal women. Urinary excretion of 5-HIAA was measured after treatment with NETA orally for 8 days, estradiol valerate orally for 9 days and a combination of both hormones for 12 days. 5-HIAA values, expressed as percentages of the pretreatment values, were significantly increased only after the estrogen treatment phase. NETA alone did not significantly alter the serotonin metabolite excretion; in combination with estradiol, the estradiol effect on serotonin metabolism was abolished. This indicates that adding norethisterone acetate to estradiol replacement therapy may have a negative impact on the effect of estradiol on serotonin metabolism.

Effect of 17 alpha-ethinylestradiol, levonorgestrel, 3-keto-desogestrel, and gestodene on calcium influx via voltage-gated calcium channels in human aortic smooth muscles.

The effect of the synthetic estradiol, 17 alpha-ethinylestradiol, and three progestogens on calcium influx was investigated in cell cultures of human aortic smooth muscle. Neither the synthetic estrogen nor the progestogens levonorgestrel, 3-keto-desogestrel, and gestodene showed, in the concentration range of 10(-9) to 10(-6) M, a significant effect on calcium influx both alone or in equimolar estrogen-gestagen combinations. The results indicate that these substances, commonly used in contraceptive pills, do not change vasotonus interfering with calcium homeostasis.

Urinary cGMP excretion after hormone replacement therapy in postmenopausal women.

It is well established that estrogens and progestogens are able to influence the vasotonus in postmenopausal women. The present study was undertaken to find out if the NO/cGMP-system is involved in this hormone action. Urinary cGMP excretion which can reflect intracellular cGMP production elicited by NO (EDRF) was investigated in 20 postmenopausal women. In an open cross-over study design norethisterone acetate was administered orally for 8 days, estradiol valerate orally for 9 days and a combination of both substances for 12 days. After all three treatment phases urinary cGMP expressed as percentage of the pretreatment value was increased at a statistically significant level. Due to high individual variations no significant differences could be found among the values after the three treatment phases. It was concluded that the NO/cGMP-system may play a role in maintaining vasotonus in postmenopausal women under hormone replacement therapy.

The influence of the dose of ethinylestradiol in oral contraceptives on follicle growth.

This prospective, randomized comparative clinical study involving 416 women investigated follicle development over a period of 12 oral contraceptive treatment cycles. Women were allocated to two groups, one group (n = 207) received a preparation containing 30 micrograms ethinylestradiol and 75 micrograms gestodene daily, and the other group (n = 209) received 20 micrograms ethinylestradiol and 150 micrograms desogestrel, daily. Follicular development was monitored by transvaginal ultrasonography of the ovaries, during days 18-21 in the pretreatment cycle and in treatment cycles 1, 3, 6, 9 and 12. Follicular development was found to be twice as frequent in the group receiving 20 micrograms ethinylestradiol/desogestrel as in the group receiving 30 micrograms ethinylestradiol/gestodene. For all cycles, follicles of 10-30 mm were found in 18% of women in the desogestrel group, compared with 9.7% in the gestodene group, whilst follicles with a diameter of >30 mm were present in 5% of the desogestrel group compared with 1.9% of the gestodene group. The difference between the treatment groups with respect to follicle diameters of 10-30 mm and >30 mm was statistically significant (p < 0.05 and p < 0.001, respectively). No ruptured follicles were observed in either group throughout the study, suggesting that there was no escape ovulation, however, there was one pregnancy in the desogestrel group that could not be explained either by drug interactions or missed pills. It can be concluded that the ethinylestradiol dose in an oral contraceptive has a significant effect on follicular ovarian activity, and that reducing the dose to 20 micrograms is associated with a significant increase in follicle size.

Influence of oral contraceptives on drug therapy.

Interferences between drugs and oral contraceptives are considered to alter pharmacokinetics and thus the efficacy of steroidal hormones. It should be noted, however, that steroids can also modify the metabolism and pharmacodynamic effects of various substances. To the present knowledge, phase I (i.e., oxidation, demethylation) and phase II reactions (conjugation) are concerned. Drugs sharing those enzymatic systems with oral contraceptives experience either an increase in bioavailability by inhibition of oxidative metabolism or undergo accelerated elimination by induced conjugation. Such interaction may be of practical interest in subjects who take oral contraceptives and are simultaneously treated with antidepressants, antihypertensives, insulin, synthetic glucocorticoids, theophylline, and caffeine.

PIP: The effects of oral contraceptives (OCs) on drug therapy are related mainly to the inhibition of microsomal oxidation as well as the induction of enzymes involved in conjugation reactions. Since many drugs share these catabolic pathways, their pharmacodynamics will be affected by OCs. Notable interactions include an increased bioavailability of analgesics, tranquilizers, and tricyclic antidepressants. OCs increase the risk for hypertension, and pharmacokinetic interactions are to be expected when OCs are administered with antihypertensive drugs. Likewise, OCs affect lipid metabolism and thus modify the effects of atherogenic drugs; however, the different forms of hyperlipidemia show a heterogeneous response to OCs. Another particular concern is that the gestagen components of OCs may cause peripheral insulin resistance and may require dose adaption with antidiabetic treatments. Two common nonprescription drugs, theophylline and caffeine, show decreased clearance rates due to OCs. All share a common oxidation pathway involving cytochrome P-450 and P-448. However, cigarette smoking stimulates these enzymes, and the decreased clearance of theophylline and caffeine is usually not observed in smokers. The reports of effects of OCs and alcohol taken together are mixed, and no clinically relevant conclusions can be drawn. Most vitamin and mineral levels are influenced by OCs, but this is a concern only under conditions of deprived diet, when normal dietary adjustments are impossible. An important caveat of the many documented effects of OCs on the pharmacodynamics of other drugs is that, in most instances, these effects will be counterbalanced with kinetic changes and result in no clinical manifestation. Nevertheless, clinicians must be aware of possible adverse reactions, particularly in predisposed patients.