Are there unmet needs in contraceptive counselling and choice? Findings of the European TANCO Study.

INTRODUCTION: Effective use of contraception requires women to make an informed choice about methods that match their individual needs and expectations. The European Thinking About Needs in Contraception (TANCO) study is a quantitative, online survey of healthcare provider and women's views on aspects of counselling around contraception and contraceptive use. METHODS: Healthcare providers and women attending their practices for contraceptive counselling were invited to complete online questionnaires. The women's survey explored knowledge and use of contraceptive methods, satisfaction with current method, and interest in receiving more information about all methods. Healthcare provider views were gathered in parallel. RESULTS: A total of 676 healthcare providers and 6027 women completed the online surveys in 11 countries. There was a high prevalence of contraceptive use and general satisfaction with current method across the countries. Fifty-five percent of women were using short-acting contraception (SAC) methods; 19% were using a long-acting reversible contraception (LARC) method. Sixty percent of women were interested in receiving more information about all methods; 73% of women said they would consider LARC if they received more comprehensive information. Healthcare providers tend to underestimate women's interest in receiving information on contraception in general and, more specifically, LARC methods. CONCLUSIONS: Despite high levels of use and satisfaction with current methods, women were interested in receiving more information about all contraceptive methods. Greater exploration of women's views on their needs and expectations of contraception could lead to increased knowledge, more effective discussions with healthcare providers and the greater likelihood of informed contraceptive choice.

ESC expert statement on the effects on mood of the natural cycle and progestin-only contraceptives.

Hormonal fluctuations during the natural cycle, as well as progestins used for hormonal contraception, can exert effects on mood especially in vulnerable women. Negative effects of levonorgestrel-releasing intrauterine contraception on mood are rare.

Effects of a combined oral contraceptive containing oestradiol valerate/dienogest on hormone withdrawal-associated symptoms: results from the multicentre, randomised, double-blind, active-controlled HARMONY II study.

The objective of this multicentre, randomised, double-blind study was to compare a combined oral contraceptive (COC) containing oestradiol valerate/dienogest (E2V/DNG) administered in a dynamic dosing regimen with a monophasic COC containing ethinyloestradiol/levonorgestrel (EE/LNG), with regard to their ability to reduce the frequency and intensity of headache and pelvic pain in women with hormone withdrawal-associated symptoms (HWAS). Women aged 18-50 years received E2V/DNG in an oestrogen step-down and progestin step-up regimen (26/2 regimen; n = 223) or EE 20 µg/LNG 100 µg (21/7 regimen; n = 218) over six cycles. Headache and pelvic pain were assessed using a visual analogue scale (VAS) during cycle days 22-28. Rescue medication use was also assessed. E2V/DNG was superior to EE/LNG with regard to reducing the frequency and intensity of headache and pelvic pain from baseline to cycle 6 (change from baseline in the average of the three highest VAS values [mean ± standard deviation]: 47.7 ± 29.4 vs 34.5 ± 25.7 mm, respectively; p < 0.0001). The use of rescue medication was also significantly reduced with E2V/DNG compared with EE/LNG (p < 0.05). E2V/DNG may be a good option for women who experience HWAS with traditional 21/7-day regimen COCs.

Proliferative effects of estradiol- or ethinylestradiol-progestogen combinations on human breast cancer cells in an intermitted and a long-term regimen.

Currently the use of natural estradiol as estrogenic component in oral contraceptives is more and more extended. It is unknown whether the application of this estrogen is associated with a different breast cancer risk as compared to the common use of the synthetic ethinylestradiol. In addition with the intention to reduce menstruation associated symptoms and bleeding periods an extended-cycle regimen is currently considered. In the present in vitro work, we have compared the effect of these different estrogenic compounds and the different treatment regimens on breast cancer risk. Human breast cancer cells (ZR75-1 and HCC1500) were incubated with equimolar concentrations of estradiol or ethinylestradiol combined with various progestogens, dienogest, drospirenone, keto-desogestrel, levonorgestrel, and nomegestrel. Usual and extended cycle was mimicked by incubation periods of 3 days with 1 day hormones off and 4 days, respectively. Molecular markers for proliferation and apoptosis were investigated by Western blot. In both cell lines estradiol and ethinylestradiol elicited a significant increase in the proliferation rate without difference between the 2 estrogens. The effect in the long-term cycle tended to be more pronounced than in the intermitted cycle. Progestogen addition most significantly reduced the estrogen-induced proliferation rate. The molecular markers were influenced by the progestogens mostly in the same manner, reducing the proliferation/apoptosis rate. Our results indicate that both estrogenic based combinations with progestogens may not increase breast cancer risk independent from the regimen, intermitted or long-term cycle. However clinical studies are necessary to prove these in vitro results.

Effects of the progestagen-only contraceptive implant Implanon on transforming growth factor beta1 and endothelin-1.

Progestagen-only contraceptives are often prescribed to women with an increased cardiovascular risk, despite the fact that only few data are available on the effect of these contraceptives on circulating biomarkers of inflammation and endothelial function. In our prospective case-control study, we aimed to investigate the influence of the low-dose etonogestrel-releasing contraceptive implant Implanon on endothelin-1 and cytokine transforming growth factor beta (TGF-beta1), both factors involved in the early phases of atherogenesis. We also were interested in searching for an interrelation between changes in these two parameters and changes in female hormones and plasma lipids. Cases (n=20) were women using Implanon for contraception, and controls (n=20) were females not using hormonal contraception. Baseline blood samples were taken during the early follicular phase of cycle 1 in both groups. A second sample was taken 12 weeks after Implanon insertion or, for controls, in the early follicular phase of cycle 4. In both groups no significant change in endothelin-1 or TGF-beta1 was observed. In Implanon users, cholesterol, high-density lipoprotein, low-density lipoprotein, sex hormone-binding globulin, and testosterone decreased significantly. No correlations were found between endothelin-1 or TGF-beta1 and the investigated parameters. The results suggest that Implanon does not exert a clinically relevant negative effect on endothelin-1 or TGF-beta.

Comparison of the proliferative effects of ethinylestradiol on human breast cancer cells in an intermittent and a continuous dosing regime.

Many women would prefer fewer bleeding episodes while taking oral contraceptives. For this reason and with the intention of reducing menstruation-associated symptoms, an extended-cycle contraceptive is considered in the present paper. However, it remains unknown whether this long-term treatment is associated with a different breast cancer risk from that of the usual treatment. Therefore, in the present in vitro work we intend to compare the effect of these different treatment regimens on breast cancer risk. MCF-7 cells (human estrogen- and progesterone-receptor-positive metastatic breast cancer cells) and HCC1500 cells (human estrogen- and progesterone-receptor-positive primary breast cancer cells) were incubated with physiological concentrations of ethinylestradiol (EE). Usual and extended cycles were mimicked by incubation periods of 18 hours with EE followed by 6 hours without EE and 24 hours with EE for 3 days, respectively. In both cell lines, EE elicited a significant increase in the proliferation rate. No significant difference was found between the two incubation periods. Our results indicate that continuously administered ethinylestradiol may not increase breast cancer risk in comparison to intermittent application. However, clinical studies are necessary to prove these in vitro results.

[Cardiovascular risks associated with low-dose combined oral contraceptives]. / Kardiovaskuläre Risiken unter der Mikropille.

The relative risk for cardiovascular events in current users of low-dosed oral contraceptives is about 2- to 3-fold greater than in nonusers. As in young women (age 20-24) the incidence for cardiovascular events is very low (51 per million woman-years) the use of modern oral contraceptives is safe in the absence of a history of smoking, hypertension, migraine, venous thromboembolism in the personal or family history and in the absence of other conventional risk factors. The cardiovascular risk is increased in women older than 35 years. This risk increases 2- to 4-fold if oral contraceptives are used and is substantially elevated in combination with additional cardiovascular risks. To minimize these risks it is essential to take a careful personal and family history and to check the blood pressure. Women with cardiovascular risks should be encouraged to use other forms of contraception, like progestagen-only methods or intrauterine devices.

Nonpalpable ultrasonographically not detectable Implanon rods can be localized by magnetic resonance imaging.

Recently, the contraceptive implant Implanon has been introduced in several European countries. In comparison to the six-capsule preparation Norplant, the removal of this single-rod system should be associated with less complications. However, the removal of nonpalpable Implanon rods can be difficult because the implant is not always visible with ultrasound. The aim of this study was to find a radiologic method for the localization of Implanon implants that are nonpalpable and can not be detected by ultrasound. X-ray, ultrasound, computed tomography, and magnetic resonance imaging (MRI) were investigated as methods to localize Implanon in a pig chest preparation and in a woman with a nonpalpable implant. The implant in the woman could be localized unequivocally only by MRI. We conclude that MRI is the best method for the unequivocal localization of nonpalpable, ultrasonographically not detectable Implanon rods. To avoid unnecessary scar tissue formation, it may be appropriate to defer surgery for the removal until definitive localization.

[Contraception in perimenopause]. / Kontrazeption in der Perimenopause.

Perimenopausal women are still potentially fertile and pregnancy is attended with increased maternal and perinatal mortality. Several contraceptive methods can be used therapeutic for the treatment of climacteric symptoms like menstrual irregularities, flushes and vaginal dryness. Low-dose oral contraceptives (OC) prevent climacteric symptoms and additionally protect from perimenopausal bone loss. However, the individual cardiovascular risk increases with age and is even higher in perimenopausal women using OCs. Therefore for women with cardiovascular risk factors sterilization, barrier methods, progestin-only methods and intrauterine devices (IUD) are the better choice. Prolonged and heavy menses can be treated with the levonorgestrel-releasing IUD or injectable progestogens. If estrogen replacement is necessary, a low-dose treatment with natural estrogens can be combined with barrier methods, the levonorgestrel-releasing IUD and injectable progestogens. The variety of contraceptive options available to perimenopausal women allows individual counseling and thus may enhance compliance.

The effect of the menstrual cycle and of ethinylestradiol on nitric oxide, endothelin-1 and homocysteine plasma levels.

The use of the estrogen ethinylestradiol is associated with an increased cardiovascular risk. It is not known whether this might be caused by an influence of ethinylestradiol on endothelium-derived factors or on the cardiovascular risk factor homocysteine. Our aim was to evaluate whether a short-term treatment with ethinylestradiol results in changes of nitric oxide (NO), endothelin-1 and homocysteine. Participants were ten healthy women with regular menstrual cycles. NO, homocysteine, endothelin-1, estradiol and progesterone were measured during one cycle and before and after treatment with ethinylestradiol at 50 microg/day. Homocysteine and NO did not change significantly during the menstrual cycle or after treatment. However, endothelin-1 levels decreased during the cycle (from 3.89 ng/l to 2.93 ng/l p < 0.05) and after ethinylestradiol (from 2.94 ng/l to 2.26 ng/l p<0.03). Analysis of the pretreatment data showed a positive correlation between homocysteine and NO and between NO and endothelin-1. Treatment with ethinylestradiol caused a shift in the balance between NO and endothelin-1 in the direction of vasodilatation. This finding is one factor concerning the effects of ethinylestradiol on the vascular system but does not explain the cardiovascular risk of this substance.

The incidence of actinomyces-like organisms in Papanicolaou-stained smears of copper- and levonorgestrel-releasing intrauterine devices.

Actinomyces-like organisms (ALOs) are a common finding in Papanicolaou-stained cervico-vaginal smears (PAP smears) of women using an intrauterine device (IUD). The incidence of ALOs positive PAP smears depends on the type of IUD. Pelvic actinomycosis is a severe disease that may require hysterectomy and salpingo-oophorectomy. In a retrospective study we compared the incidence of ALOs positive PAP smears in users of the new levonorgestrel-releasing intrauterine device (LNG-IUD) (n = 52) with the incidence in Multiload Copper IUD (ML375) users (n = 104). All IUDs had been inserted from 1996-1998. Women with a follow-up period of more than 9 months were included into the final analysis (LNG-IUD: n = 34; ML375: n = 65). The incidence of ALOs in LNG-IUD users (2.9%) was significantly lower than in ML375 users (20%). Clinical consequences of ALOs positive PAP smears are discussed controversially. The low incidence in the LNG-IUD users probably leads to less IUD-removals, reinsertions and less pelvic-inflammatory-diseases.

A prospective study on the effects of depot medroxyprogesterone acetate on trabecular and cortical bone after attainment of peak bone mass.

OBJECTIVE: To study the annual change of bone mass in women aged 30-45 years being treated with depot medroxyprogesterone acetate (DMPA) in order to evaluate whether the bone mass depends on the duration of DMPA use or the oestradiol level. DESIGN: Prospective longitudinal study over an interval of 12 months. SETTING: A family planning centre of a university hospital. PATIENTS: Thirty-six current users of DMPA. INTERVENTIONS: Injection of 150 mg DMPA every 12 weeks. MEASUREMENTS: Bone mass was measured at the distal radius by peripheral quantitative computed tomography (reproducibility 0.3%). RESULTS: Mean annual changes (SD) in trabecular and cortical bone mass were 0.06 (1.6%) [P = 0.8] and -0.26% (0.6) [P < 0.04]. The decrease in cortical bone mass was not significant because the changes were within the precision error of the method used for the measurements. Duration of DMPA use and oestradiol levels were not associated to the bone parameters. CONCLUSION: We did not find a negative impact of DMPA on the bone mass of premenopausal women aged 30-45 years.

Efficacy and tolerability of a monophasic oral contraceptive containing ethinylestradiol and drospirenone.

OBJECTIVE: To assess the contraceptive reliability, cycle control and tolerability of a new monophasic oral contraceptive containing 30 g ethinylestradiol plus 3 mg drospirenone (Yasmin, Schering AG, Berlin, Germany), it was compared with an established oral contraceptive containing 30 g ethinylestradiol plus 150 g desogestrel (Marvelon, NV Organon, Oss, The Netherlands). METHODS: A randomized, open-label, 13-cycle study was performed at 80 European centers. Contraceptive reliability, cycle control, blood pressure, body weight, the incidence of adverse events and skin condition were assessed during 13 cycles of oral contraceptive use, and at follow-up. Subjects recorded body weight on three consecutive days pretreatment and weekly thereafter. RESULTS: Of 2069 women who started the study and received the trial preparations in a ratio of 4:1 (ethinylestradiol/drospirenone, n = 1657; ethinylestradiol/desogestrel, n = 412), 1615 completed the 13 cycles plus follow-up, providing data for over 23,000 evaluable cycles. Eleven pregnancies occurred during treatment, only one of which (in the ethinylestradiol/drospirenone group) could not be ascribed to user failure or interaction with other factors. Both preparations provided effective contraception and cycle control. Pre-existing acne and seborrhea were improved and blood pressure was essentially unchanged. The two treatments differed in their effect on body weight, the difference being statistically significant. In the ethinylestradiol/drospirenone group, there was a distinct decrease over the whole treatment phase, while a subtle and less distinct decrease was documented in the ethinylestradiol/desogestrel group. CONCLUSIONS: The combination of 30 g ethinylestradiol/3 mg drospirenone provides effective oral contraception, excellent cycle control, good tolerability and a level of weight loss that may have a significant beneficial effect on compliance in women with a tendency to weight gain due to water retention.

[Early premature rupture of fetal membranes and risk of lung hypoplasia in the fetus. Case report from the 22d week of pregnancy with delivery in the 30th week of pregnancy]. / Früher vorzeitiger Blasensprung und Risiko einer Lungenhypoplasie beim Feten. Fallbericht aus der 22. Schwangerschaftswoche mit Entbindung in der 30. Schwangerschaftswoche.

We report on a case of ruptured foetal membranes in the 22nd week of pregnancy. A possible risk is pulmonary hypoplasia. Although factors exist that predispose to the occurrence of pulmonary hypoplasia, the diagnosis cannot be predicted prenatally. As pulmonary hypoplasia is associated with a high neonatal mortality rate, prenatal detection would be helpful in the clinical management of early premature rupture of the membranes.