The drospirenone (DRSP)-only pill: clinical implications in the daily use.

OBJECTIVES: Progestins used in contraception are either components of combined hormonal contraceptives or are used as a single active ingredient. Progestins are highly effective in long-term contraception and have a very good safety profile with very few contraindications. METHODS: An oestrogen-free ovulation inhibitor POP has been authorised in the USA and the EU. It contains 4 mg of drospirenone (DRSP). The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular- phase levels, preventing oestrogen deficiency. RESULTS: Clinical trials have demonstrated high contraceptive effectiveness, a very low risk of cardiovascular risk events and a favourable bleeding pattern. Due to the long half-life of DRSP (30-34 h), the effectiveness is maintained even in case of a forgotten pill on a single occasion. Studies involving deliberate 4 days in one cycle 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. CONCLUSIONS: This review article will describe the clinical impact in the daily use of the 4 mg DRSP only pill and the resulting data on the effectiveness and safety of this hormonal contraceptive.

The 4 mg drospirenone-only pill improves the bleeding profile in comparison to 0.075 mg desogestrel and achieves high contraceptive efficacy even with a 24 h missed pill window.

[MHT: How and how long in healthy women above 65?] / Menopausale Hormontherapie: Wie und wie lange für gesunde Frauen über 65?

MHT: How and how long in healthy women above 65? Abstract. In Europe, women spend more than one third of their lifetime in the postmenopause which is characterized by chronic estrogen deficiency. About 80 % of them suffer from vasomotor symptoms which can last for up to twelve years or more. Menopausal hormone therapy (MHT) with sexual steroids is the most effective treatment resulting in a reduction of hot flushes and an improvement of quality of life. Today, a large proportion of women is not treated adequately as demonstrated by a marked decline of MHT-prescriptions. The postmenopause is not only associated with climacteric symptoms, but also with long-term risks, such as cardiovascular events, osteoporosis, cognitive dysfunction or diabetes mellitus. Numerous studies have shown beneficial effects of MHT on many of these diseases and on mortality, provided that treatment has been initiated close to the onset of menopause. Accordingly, some investigators have postulated a possible role of MHT in primary prevention. However, concerning long-term beneficial effects of MHT in women beyond the age of 65 years, the optimal duration of MHT is still unknown. Consequently, the duration of MHT should always be planned individually after thorough consideration of potential benefits and risks in agreement with the patient. Especially with advancing age transdermal application of estrogens seems to be the best option because of less vascular risks. There is no apodictic limitation of maximal duration of MHT.

Oral Progestins in Hormonal Contraception: Importance and Future Perspectives of a New Progestin Only-Pill Containing 4 mg Drospirenone.

Hormonal contraceptives are an effective and safe method for preventing pregnancy. Progestins used in contraception are either components of combined hormonal contraceptives (tablets, patches or vaginal rings) or are used as a single active ingredient in progestin mono-preparations (the progestin-only pill (POP), implants, intrauterine systems or depot preparations). Progestins are highly effective in long-term contraception when used properly, and have a very good safety profile with very few contraindications. A new oestrogen-free ovulation inhibitor (POP) has recently been authorised in the USA and the EU. This progestin mono-preparation contains 4 mg of drospirenone (DRSP), which has anti-gonadotropic, anti-mineralocorticoidic and anti-androgenic properties. The hormone administration regimen of 24 days followed by a 4-day hormone-free period was chosen to improve bleeding control and to maintain oestradiol concentrations at early follicular-phase levels, preventing oestrogen deficiency. Clinical trials have demonstrated a high contraceptive effectiveness, a very low risk of cardiovascular side effects and a favourable menstrual bleeding pattern. Due to the long half-life of DRSP (30 - 34 hours), the effectiveness of the preparation is maintained even if a woman forgets to take a pill on a single occasion. Studies involving deliberate 24-hour delays in taking a pill have demonstrated that ovulation inhibition is maintained if a single pill is missed. Following a summary of the current status of oestrogen-free contraception, this review article will describe the clinical development programme of the 4 mg DRSP mono-preparation and the resulting data on the effectiveness and safety of this new oestrogen-free oral hormonal contraceptive.

Correction: Oral Progestins in Hormonal Contraception: Importance and Future Perspectives of a New Progestin Only-Pill Containing 4 mg Drospirenone.

[This corrects the article DOI: 10.1055/a-1471-4408.][This corrects the article DOI: 10.1055/a-1471-4408.].

Effectiveness and safety of follitropin alfa (Ovaleap®) for ovarian stimulation using a GnRH antagonist protocol in real-world clinical practice: a multicenter, prospective, open, non-interventional assisted reproductive technology study.

BACKGROUND: The use of recombinant human follicle-stimulating hormone (r-hFSH) in ovarian stimulation protocols for infertility treatment in assisted reproductive technology (ART) clinical practice is well established. More recent advancements include the availability of biosimilar r-hFSH products, which expand the choices available to healthcare practitioners and patients. Better understanding of how such a product contributes to routine clinical practice is valuable to help prescribers make informed treatment choices. The objective of this study was to examine the effectiveness and safety of ovarian stimulation (OS) with follitropin alfa (Ovaleap®) for routine IVF or intracytoplasmic sperm injection treatment in gonadotropin-releasing hormone (GnRH) antagonist cycles in real-world ART clinical practice. METHODS: This non-interventional, multicenter, prospective study was initiated in 34 specialized reproductive medicine centers in Germany. Eligible women were 18-40 years old with a body mass index < 30 kg/m2, menstrual cycle 24-35 days and anti-Müllerian hormone ≥1 ng/mL, who were undergoing a first OS cycle exclusively with Ovaleap® during routine ART using a GnRH antagonist protocol. Primary effectiveness outcomes were number of retrieved oocytes after OS and clinical pregnancy rate (CPR). Secondary outcomes included fertilization rate, number of transferred embryos, live birth delivery rate, safety, and user satisfaction with the Ovaleap® pen. RESULT(S): Of 507 women screened, 463 received at least 1 dose of Ovaleap® and 439 had Visit 2 data (per protocol population; PPP). The mean(±SD) number of retrieved oocytes was 11.8 ± 7.2 (PPP). The CPR among women with documented embryo transfer was 41.3% (158/383), resulting in a live birth delivery rate of 31.6% (138/437) among PPP patients with available follow-up information. Overall, 8.6% (40/463) of women reported ≥1 adverse drug reaction. Ovarian hyperstimulation syndrome occurred in 23 (5.0%) patients, rated mild in 14 (3.0%), moderate in 8 (1.7%), and severe in 1 (0.2%). Patients reported high user satisfaction and high convenience with use of the Ovaleap® pen. CONCLUSION: The effectiveness and safety of OS with Ovaleap® in a GnRH antagonist protocol were extended to real-world ART clinical practice for the first time. TRIAL REGISTRATION: Registered on 22 June 2016 (retrospectively registered) at ClinicalTrials.gov (NCT02809989).

Extended-cycle versus conventional treatment with a combined oral contraceptive containing ethinylestradiol (30 µg) and levonorgestrel (150 µg) in a randomized controlled trial.

The objective was to assess efficacy and safety of a combined oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in an extended-cycle vs. a conventional-cycle regimen. This first European randomized, active controlled, open, prospective, parallel-group trial was conducted in 48 German gynecological centers. 1,314 healthy, sexually active women aged 18-35 years were randomized. With an unadjusted PI of 0.483 (upper 95% CI: 1.237), the extended-cycle regimen fulfilled the contraceptive efficacy of EE/LNG, the requirements of the European Medicines Agency. The mean total number of bleeding days per year was significantly lower in the extended-cycle vs. the conventional-cycle regimen. Analyses of bleeding patterns showed a reduced total number of bleeding/spotting days per year in the extended-cycle vs. the conventional-cycle regimen. Cycle-associated complaints and AE were comparable in both groups. Both regimens were very well accepted. The extended-cycle regimen of EE/LNG was effective and well tolerated resulting in a lower number of bleeding days and a favorable bleeding pattern compared to the conventional-cycle regimen.

Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking.

BACKGROUND: Modulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. METHODS AND RESULTS: We measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane. CONCLUSION: Elevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues.

Adherence with ethinylestradiol 20 µg/drospirenone 3 mg in a flexible extended regimen supported by the use of a digital tablet dispenser with or without acoustic alarm: an open-label, randomized, multicenter study.

OBJECTIVE: To evaluate the effect of a digital dispenser's acoustic alarm function on adherence to ethinylestradiol (EE) 20 µg/drospirenone 3 mg in a flexible extended regimen (EE/drospirenoneFlex) among women in five European countries (France, Germany, Italy, Spain, UK) seeking oral contraception. STUDY DESIGN: Randomized, parallel-group open-label study. METHODS: Women aged 18-35 years received EE/drospirenoneFlex administered in a regimen with cycle lengths of their choice with the aid of a digital pill dispenser over 1 year. In group A (N=250), the dispenser's acoustic alarm was activated (ie, acoustic alarm + visual reminder). In group B (N=249), the acoustic alarm was deactivated (ie, visual reminder only). In addition, the women recorded pill intake daily in diary cards. The primary efficacy variable was the mean delay of daily pill release after the dispenser reminded the woman to take a pill (reference time). Secondary efficacy variables included number of missed pills, contraceptive efficacy, bleeding pattern, tolerability, and user satisfaction. RESULTS: Dispenser data showed a mean (standard deviation [SD]) daily delay in pill release of 88 (126) minutes in group A vs 178 (140) minutes in group B (P<0.0001). Median (lower quartile, Q1; upper quartile, Q3) number of missed pills was 0 (0; 1) in group A vs 4 (1; 9) in group B (P<0.0001). Diary card results revealed similar trends; however, underreporting of missed pills was evident in both groups. No pregnancies were reported during 424 women-years of exposure. Across the two groups, the mean (SD) EE/drospirenoneFlex cycle length was 51.0 (31.8) days with strong regional differences, and the mean (SD) number of bleeding/spotting days was 50.4 (33.0) days. EE/drospirenoneFlex was well tolerated, and 80% of women were satisfied with treatment. CONCLUSION: The dispenser's activated acoustic alarm improved adherence with daily tablet intake of EE/drospirenoneFlex, reducing missed pills. EE/drospirenoneFlex provided effective contraception and a good tolerability profile.

Effect of a low-dose contraceptive patch on efficacy, bleeding pattern, and safety: a 1-year, multicenter, open-label, uncontrolled study.

This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD. Participants were women aged 18 to 35 years, all of whom received the EE/GSD patch for 13 cycles each of 21 treatment days (one patch per week for 3 weeks) followed by a 7-day, patch-free interval. The primary efficacy variable was the occurrence of unintended pregnancies during the study period as assessed by life table analysis and the Pearl Index. Secondary efficacy variables were days with bleeding during four 90-day reference periods and during 1 treatment year, bleeding pattern, and cycle control. The Kaplan-Meier probability of contraceptive protection after 364 treatment days was 98.8% and the adjusted Pearl Index was 0.81. The percentage of participants with intracyclic bleeding/spotting decreased over time, from 11.4% to 6.8% in cycles 1 and 12, respectively. Almost all participants (range: 90.8%-97.6%) experienced withdrawal bleeding across the study period. Compliance was very high (mean: 97.9%; median: 100%). The most frequent adverse events were headache (9.5%) and application site reaction (8.5%); no clinically significant safety concerns were observed. Results suggest the EE/GSD patch is highly effective in preventing pregnancy. Menstrual bleeding pattern was favorable and within the ranges expected of a healthy female population. The patch was well tolerated and treatment compliance was high.

Hormonal contraception--what kind, when, and for whom?

BACKGROUND: In Germany today, one-third of the 20 million women of child-bearing age use combined oral contraceptives (COCs). In this article, we summarize the current knowledge of the mode of action, wanted and unwanted side effects, and long-term risks of COCs. The levonorgestrel intrauterine device (IUD) and long-acting injectable or implantable monophasic progestogen preparations offer comparable contraceptive efficacy to COCs. Nonetheless, they are less frequently used in Germany than COCs, because of their propensity to cause breakthrough bleeding. METHOD: Selective review of the literature. RESULTS: COCs suppress gonadotropin secretion and thereby inhibit follicular maturation and ovulation. Their correct use is associated with 0.3 pregnancies per 100 women per year, their typical use, with 1 pregnancy per 100 women per year (Pearl index). COCs have effects on the cardiovascular and hemostatic systems as well as on lipid and carbohydrate metabolism. When given in the presence of specific risk factors, they significantly increase the likelihood of cardiovascular disease and thromboembolism. Women with persistent human papilloma virus (HPV) infection who take COCs are at increased risk of developing invasive cervical cancer. On the other hand, COCs lower the cumulative incidence of endometrial and ovarian cancer by 30% to 50%, and that of colorectal cancer by 20% to 30%. Other malignancies seem to be unaffected by COC use. CONCLUSION: As long as personal and familial risk factors are carefully considered, COCs constitute a safe, reversible, and well-tolerated method of contraception.

Effect of extended-cycle regimen with an oral contraceptive containing 30 mcg ethinylestradiol and 2 mg dienogest on bleeding patterns, safety, acceptance and contraceptive efficacy.

BACKGROUND: The present study compared the efficacy and safety of a combined oral contraceptive containing 30 mcg ethinylestradiol and 2 mg dienogest (EE/DNG) in conventional and extended-cycle regimen over 1 year of treatment. STUDY DESIGN: In a phase III, randomized, prospective, open, two-arm, multicenter study, 1315 sexually active women (range, 18-40 years) were treated with EE/DNG either conventionally (21/7 days) or according to an extended-cycle regimen (84/7 days). Data were documented on volunteer diaries, and adverse events (AEs) were reported during five visits. RESULTS: In the extended-regimen group, the total number of days with bleeding progressively decreased over time, and overall, the volunteers had fewer numbers of days with bleeding/spotting compared to those treated conventionally. Intracyclic bleeding, on the other hand, was more frequent in the extended-cycle group, although its frequency considerably decreased over time. Both regimens offered reliable contraception, with an unadjusted Pearl Index of 0.489 for the conventional regimen and 0.495 for the extended regimen. The number of AEs was higher in the extended-cycle group, although the group differences tended to decrease over time. CONCLUSIONS: Extended-cycle use of EE/DNG was effective and mostly well tolerated, appearing to be a favorable option for women who need or wish to omit the pill-free interval.

Disseminated tumor cells in the bone marrow of patients with ductal carcinoma in situ.

Detection of disseminated tumor cells (DTCs) in bone marrow is an independent prognostic factor in primary breast cancer. Here, we conducted a proof-of-principle study to evaluate whether this tumor cell spread occurs already in patients with ductal carcinoma in situ (DCIS). After preoperative screening by stereotactic core biopsy, 30 consecutive women with DCIS were included. Bone marrow aspirates, taken at the time of primary surgery, were subjected to DTC detection by a standardized immunoassay using the established monoclonal anti-cytokeratin antibodies A45-B/B3 and AE1/AE3. DTCs were detected in 4 of 19 cases of pure DCIS (21.1%) and in four of seven cases of DCIS with microinvasion (57.1%). After a median follow-up time of 22 months, two initially DTC-positive patients suffered from contralateral carcinoma and contralateral DCIS at months 12 and 30, respectively, whereas the remaining patients were relapse free. Thus, hematogenous tumor cell dissemination into bone marrow is an early event in breast cancer development.

SATB1 gene expression and breast cancer prognosis.

Recently it has been shown that the genome organizer SATB1 plays an important role in breast cancer progression and predicts a poor prognosis. However its prognostic value compared to markers as the estrogen receptor is currently unclear. The expression levels of SATB1 mRNA from Affymetrix microarray in a cohort of 2058 breast cancer samples and its prognostic impact were analyzed. There was no significant difference in disease-free survival among ER negative cancers but instead a benefit for high SATB1 expression among ER positive tumors (p = 0.042). However, even in ER positive cancer no independent prognostic value in multivariate analysis with standard parameters was observed. Thus the use of SATB1 as target or prognostic marker for breast cancer should be viewed with caution and a possible confounding effect of the estrogen receptor status of the tumor should be taken into account when analysing new markers as SATB1.

Prescribing preferences and personal experience of female gynaecologists in Germany and Austria regarding use of extended-cycle oral contraceptives.

OBJECTIVES: To investigate prescribing preferences and personal experience of female gynaecologists with extended-cycle use of combined oral contraceptives (COCs) in Germany and Austria. METHODS: A questionnaire on prescribing patterns and personal experience with extended COC regimens was delivered to female gynaecologists practising in Germany and Austria. RESULTS: Of 2,500 delivered questionnaires, 1,113 were returned. After exclusion of 22 invalid questionnaires, the remaining 1,091 (43.6% of delivered questionnaires) remained eligible for analysis and were considered as the full analysis set (100%). Nearly all gynaecologists (97%) reported prescription of extended-cycle regimens to their patients, independent of their personal experience as users. The main medical reasons for prescription were cycle-related headache (93.8%), dysmenorrhoea (88.2%), cycle-related complaints (74.5%), and hypermenorrhoea (70.9%). In total, 863 gynaecologists had personally used COCs, 321 (37.2%) in extended-cycle regimen. The most commonly employed combinations were 30 µg ethinylestradiol (EE) + 2 mg dienogest (n = 114; 37.5%) and 30 µg EE + 3 mg drospirenone (n = 69; 22.7%). CONCLUSIONS: Although considered off-label use, extended-cycle use of COCs is widely prescribed and personally used by German and Austrian female gynaecologists. The lack of personal experience with extended-cycle use does not impair the prescribing habit of gynaecologists with regard to extended-cycle regimens.

Pregnancy after the calcium ionophore correction of pronuclei position in oocytes after intracytoplasmic sperm injection.

OBJECTIVE: To report a successful pregnancy after transfer of embryos derived from oocytes after calcium ionophore correction of the pronuclei localization after intracytoplasmic sperm injection (ICSI). DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 30-year-old patient and her 30-year-old husband, diagnosed with asthenoteratozoopermia, underwent ICSI because of three unsuccessful IUI attempts. INTERVENTION(S): Thirteen metaphase II oocytes were injected with morphologically normal spermatozoa and immediately divided into two groups. Group 1 (n = 7) was the untreated control and in group 2 (n = 6), the oocytes were treated with 10 µM calcium ionophore solution for 20 minutes at 37°C in 6% CO(2). The fertilization was checked 18 hours later and location of pronuclei in cytoplasm was assessed. Transfer of two embryos was performed on the third day after oocyte retrieval. MAIN OUTCOME MEASURE(S): Pregnancy after transfer of embryos after calcium ionophore correction of pronuclei localization. RESULT(S): Fertilized zygotes from calcium ionophore-treated oocytes with physiologically normal central localization of pronuclei were chosen for ET. Clinical pregnancy was confirmed at 7 weeks of gestation. CONCLUSION(S): Post-ICSI calcium ionophore activation of oocytes can be used for correction of the pronuclei localization, which can increase developmental rate of embryos.

Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on lipid metabolism during 1 year of conventional or extended-cycle use.

BACKGROUND: The effects of extended regimens of combined oral contraceptives (COC) on lipid parameters are largely unknown. The present study compared the effects of a COC containing 30 mcg ethinyl estradiol and 2 mg dienogest (EE/DNG) in conventional and extended-cycle regimen over 1 year. STUDY DESIGN: Lipid parameters were measured in 59 women treated with EE/DNG either conventionally (21+7 days) or in extended-cycle regimen (84+7 days). Blood samples were taken in a control cycle and at 3 and 12 months of treatment. RESULTS: The mean levels of total cholesterol, HDL cholesterol and HDL(2) cholesterol underwent modest to moderate significant increases over time, while the significant increase in triglycerides and VLDL cholesterol was more pronounced with both regimens. LDL cholesterol decreased slightly in both regimen groups, whereas lipoprotein(a) was transiently decreased at 3 months only in the extended-cycle group. The changes reached a steady-state at latest at 3 months, but did not exceed the given normal ranges for any of the parameters. Notably, except for lipoprotein(a), the changes in mean lipid levels were not significantly different in the conventional and the extended-cycle regimen at 3 or 12 months of treatment. CONCLUSION: Use of EE/DNG in conventional or extended-cycle regimen resulted in comparable changes of lipid parameters.

Effects of conventional or extended-cycle regimen of an oral contraceptive containing 30 mcg ethinylestradiol and 2 mg dienogest on various hemostasis parameters.

BACKGROUND: The study was conducted to investigate the effect of a combined oral contraceptive (COC) containing 30 mcg ethinylestradiol and 2 mg dienogest with two different regimens on various hemostasis variables. STUDY DESIGN: Hemostatic parameters were measured in 59 women treated with a monophasic COC containing 30 mcg ethinylestradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or with an extended-cycle regimen (4 extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21-26 of the preceding control cycle and on Days 19-21 of the 3rd and 13th conventional cycle or on Days 82-84 of the first and fourth extended cycle. RESULTS: After 3 and 12 months, significant increases in fibrinogen (20%), factor VII antigen (50-60%), factor VII activity (45%), activated factor VII (30-45%) and factor VIII activity (10-20%) occurred in both treatment regimens. In both groups, there was a small but significant decrease in the level and activity of antithrombin, a 20-25% decrease in total and free protein S and a 15-20% rise in the level and activity of protein C, but no significant change of the thrombin-antithrombin complex. A significant over-time rise by about 25% of prothrombin fragment 1+2 occurred only in the extended-cycle group, but this effect did not differ significantly from that observed during conventional treatment. Plasminogen was elevated by 50% in both groups, while tissue-plasminogen activator (t-PA) activity rose by 15% in the conventional group and by 25-30% in the extended-cycle group. In both groups, t-PA antigen was reduced by about 30% and plasminogen activator inhibitor-1 by 40-60%. The levels of the plasmin-antiplasmin complex rose by 30-40% and those of D-dimers by 20-55%. The prothrombin time was slightly increased and the activated partial thromboplastin time was slightly decreased. CONCLUSION: In general, these results were in agreement with those observed during treatment with other COCs. The study demonstrated that during conventional and extended-cycle treatment with EE/DNG, a steady-state in the effects on hemostasis variables was reached within 3 months, and that the effects observed after 3 and 12 months of treatment did not substantially differ between conventional and extended-cycle regimen.

Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters: conventional vs. extended-cycle use.

BACKGROUND: This study was conducted to investigate the effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on thyroid hormones and androgen parameters. STUDY DESIGN: Thyroid and androgen parameters were measured in 59 women treated with a monophasic combined oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest (EE/DNG) either conventionally (13 cycles with 21 days of treatment+7 days without hormones) or according to an extended-cycle regimen (four extended cycles with 84 days of continuous administration of EE/DNG, followed by a hormone-free interval of 7 days). Blood samples were taken on Days 21-26 of the preceding control cycle and on Days 19-21 of the 3rd and 13th conventional cycle, or on Days 82-84 of the first and fourth extended cycle. RESULTS: At both time points, the serum concentrations of thyroxine-binding globulin were elevated by about 65% in both treatment regimens. Likewise, both groups showed an increase in total triiodothyronine (T3) and total thyroxine (T4) by 30-40%, and no change in free T4. Until the 12th month of conventional treatment, the level of free T3 remained unchanged but decreased slightly during the extended-cycle regimen. In both groups there was a rise of sex hormone-binding globulin by 210-230% after 3 months and by 220-250% after 12 months. The levels of total testosterone were reduced by about 40% and those of free testosterone by 55-65% after 3 and 12 months. CONCLUSION: The results suggest that, during conventional and extended-cycle treatment with EE/DNG, a steady state in the effects on thyroid hormones and androgen parameters was reached within 3 months and that the changes in the various hormonal parameters did not substantially differ between conventional and extended-cycle regimen.

Umbilical endometriosis in pregnancy without previous surgery.

OBJECTIVE: To illustrate the influence of pregnancy on primary umbilical endometriosis. DESIGN: Case report. SETTING: Gynecologic endocrinology outpatient department of a university hospital. PATIENT(S): 27-year-old nulliparous woman. INTERVENTION(S): Surgical treatment with total excision of the umbilicus during early pregnancy. MAIN OUTCOME MEASURE(S): Progressive enlargement of endometriotic umbilical lesions during pregnancy. RESULT(S): At 3-month follow-up evaluation, there were no signs of recurrence of the disease. CONCLUSION(S): Spontaneous umbilicus endometriosis is a rare disease that can worsen during pregnancy.