Combination Of Ethinylestradiol Research Articles

Modulatory Effects of Ethinyl Estradiol Plus Drospirenone Contraceptive Pill on Spontaneous and GnRH-Induced LH Secretion

Background: Combined oral contraceptives (COCs) work mostly by preventing the pre-ovulatory gonadotropin surge, but the action of COCs on spontaneous episodic and GnRH (gonadotropin-releasing hormone)-induced LH (luteinizing hormone) release has been poorly evaluated. Oral contraceptives are known to act on the spontaneous hypothalamic–pituitary functions reducing both GnRH and gonadotropin release and blocking ovulation. Aim: To evaluate spontaneous and GnRH-induced LH release during both phases of the menstrual cycle or under the use of the contraceptive pill. Methods: A group of 12 women, subdivided into two groups, volunteered for the study. Group A (n = 6, controls) received no treatments, while Group B (n = 6) received a 21 + 7 combination of ethinyl-estradiol (EE) 30 µg + drospirenone (DRSP) 3 mg. Both groups were evaluated twice: Group A during follicular and luteal phases, Group B during pill assumption and during the suspension interval, performing a pulsatility test, GnRH stimulation test, and hormonal parameters evaluation. Spontaneous and GnRH-induced secretory pulses were evaluated, as well as the instantaneous secretory rate (ISR). Results: COC treatment lowered LH and FSH (follicle stimulating hormone) levels significantly if compared to the follicular phase of spontaneous cycles. During the suspension interval, hormone levels rapidly rose and became comparable to those of the follicular phase of the control group. The LH pulse frequency under COC administration during the suspension interval was similar to that observed during the follicular phase (2.6 ± 0.3 pulses/180 min and 2.3 ± 0.2 pulses/180 min, respectively). The GnRH-induced LH peaks were greater in amplitude and duration than those observed after ISR computation in both groups. The GnRH-induced LH release during the luteal phase of the control subjects was higher than in the follicular phase (51.2 ± 12.3 mIU/mL and 14.9 ± 1.8 mIU/mL, respectively). Conversely, subjects under COC showed a GnRH-induced LH response similar during COC and during the suspension interval. Conclusions: Our data support that the EE + DRSP preparation acts on both spontaneous pulsatile release and GnRH-induced LH release during the withdrawal period of the treatment, and that after 5–7 days from the treatment suspension, steroidal secretion from the ovary is resumed, such as that of androgens. This suggests that in hyperandrogenic patients, a suspension interval as short as 4 days might be clinically better.

Metabolomic Profiling of Hormonal Contraceptive Use in Young Females Using a Commercially Available LC-MS/MS Kit.

Oral hormonal contraceptive users carry the risk of venous thrombosis and increased mortality. This study aimed to comprehensively profile the serum metabolome of participants using a combination of drospirenone (DRSP) and ethinyl estradiol (EE) containing oral contraceptives (COCs). The MxP Quant 500 kit for liquid chromatography mass tandem spectrometry (LC-MS/MS) was used to analyse the 22 controls and 44 COC users (22 on a low EE dose (DRSP/20EE) and 22 on a higher EE dose (DRSP/30EE)). The kit's results were compared to our internally developed untargeted and targeted metabolomics methods previously applied to this cohort. Of the 630 metabolites included in the method, 277 provided desirable results (consistently detected above their detection limits), and of these, 5 had p-values < 0.05, including betaine, glutamine, cortisol, glycine, and choline. Notably, these variations were observed between the control and COC groups, rather than among the two COC groups. Partial least squares-discriminant analysis revealed 49 compounds with VIP values ≥ 1, including amino acids and their derivatives, ceramides, phosphatidylcholines, and triglycerides, among others. Ten differential compounds were consistent with our previous studies, reinforcing the notion of COCs inducing a prothrombotic state and increased oxidative stress. Although only a limited number of compounds were deemed usable, these were quantified with high reliability and facilitated the identification of meaningful biological differences among the sample groups. In addition to substantiating known drug-induced variations, new hypotheses were also generated.

Hormonal contraception use and insomnia: A nested case-control study

Evidence is limited concerning possible associations between the use of hormonal contraception and insomnia. We applied the nested case-control design on a nationwide sample of women, aged 15–49 years, derived from national health care registries to characterize the association between the use of hormonal contraception and the occurrence of insomnia. There were altogether 294,356 users and 294,356 non-users of hormonal contraception. 11,105 new cases of insomnia emerged among the 1,148,969 person-years of the follow-up period of two years. All the significant associations of hormonal contraception with insomnia emerged among the participants aged 34 years or younger, and if only the tertiary care data was concerned, among the those aged 15–19 years. The users of the fixed combination of drospirenone and ethinylestradiol as well as that of cyproterone and ethinylestradiol had significantly decreased odds for insomnia, whereas the users levonorgestrel-releasing intrauterine devise as well as those of vaginal ring with etonogestrel and ethinylestradiol had significantly increased odds for insomnia as compared with non-users. Our findings suggest that different products prescribed for hormonal contraception may be differentially associated with the occurrence of insomnia.

Chronic treatment with hormonal contraceptives alters hippocampal BDNF and histone H3 post-translational modifications but not learning and memory in female rats

Hormonal contraceptives prevent ovulation with subsequent reduction in endogenous levels of estradiol, progesterone and its neuroactive metabolite allopregnanolone. These neurosteroids modulate several brain functions, including neuronal plasticity, cognition and memory. We hypothesized that hormonal contraceptives might affect synaptic plasticity, learning and memory, as a consequence of suppressed endogenous hormones levels. Female rats were orally treated with a combination of ethinyl estradiol (EE, 0.020 mg) and levonorgestrel (LNG, 0.060 mg) once daily for four weeks. Decreased hippocampal brain-derived neurotrophic factor (BDNF) levels and altered histone H3 post-translational modifications (PTMs) were observed 14 days after discontinuation from chronic EE-LNG treatment. These effects were not accompanied by alterations in long-term plasticity at glutamatergic synapses, recognition memory in the novel object and novel place location tests, or spatial learning, memory, and behavioral flexibility in the Morris water maze test. Thus, decreased BDNF content does not affect synaptic plasticity and cognitive performance; rather it might be relevant for the occurrence of certain psychiatric symptoms, reported by some women using hormonal contraceptives. These results provide the first evidence of hippocampal epigenetic changes induced by hormonal contraceptives and complement previous studies on the neurobiological actions of hormonal contraceptives; the finding that effects of chronic EE-LNG treatment on BDNF content and histone PTMs are observed 14 days after drug discontinuation warrants further investigation to better understand the implications of such long-term consequences for women's health.

Predictable benefits of folate-containing combined oral contraceptives after abortion in women: review

Despite all prevention and education campaigns, the rate of unintended pregnancies is 40% of the more than 200 million pregnancies occurring worldwide. About half of them end in abortion. Women in the 2030 age group, where abortions peak, have not yet fulfilled their reproductive plans. The lack of competent post-abortion rehabilitation for women, including contraception counselling, results in one in three choosing a less effective method, and one in four not using any contraceptive methods at all. According to the The World Health Organization Guidelines for Safe Abortion, all women should use hormonal contraception after spontaneous or induced abortion. Combined oral contraceptives (OCs) with 30 mcg ethinyl estradiol in combination with drospirenone, which has strong antigonadotropic activity, can effectively suppress hypothalamic-pituitary-ovarian axis excitability after abortion. OCs can be used to prevent neural tube defects in the case of pregnancy after withdrawal of OCs. The use of folate-containing OCs is a sensible means of folate supplementation in women of reproductive age that may guarantee a future healthy pregnancy and overall health.

Polycystic Ovary Syndrome

Excess ovarian activity, chronic anovulation, and androgen excess are the common traits of polycystic ovary syndrome (PCOS). Several advances have been made in understanding the pathophysiology in the process of finding quicker and more effective management measures. Androgen excess in PCOS was found to correlate with markedly elevated luteinizing hormone pulsatility. Impaired insulin response is also attributed to PCOS. Regimen with 3 mg drospirenone + 20 μg ethinyl estradiol combination is beneficial for hormonal imbalance and lipid profile while having a substantial safety profile. Clinical evidence has demonstrated that a 40:1 combination of Myo-inositol and D-chiro-inositol restores ovulation in PCOS women. For women with clomiphene citrate-resistant PCOS, laparoscopic ovarian drilling has proved to be a safe and effective surgical alternative. PCOS is also an indication of bariatric surgery. To conclude, constitutional management by a multidisciplinary team may be helpful for women with PCOS. Lifestyle interventions are best advised and, in so doing, decrease body adiposity and recuperate their metabolic and reproductive health.

Ra-223 and Ethinylestradiol Combination Therapy in Castration-resistant Prostate Cancer.

Ra-223 is a therapeutic agent for bone metastatic castration-resistant prostate cancer (mCRPC). We examined the efficacy of a treatment method using Ra-223 together with ethinylestradiol (EE). Patients who received Ra-223 three or more times were included and two groups (with or without EE) were compared retrospectively. Eighteen patients were treated with Ra-223 and EE concomitantly (EstRadium therapy) and 13 patients were treated with Ra-223 alone or Ra-223 and agents other than EE (non-EstRadium therapy). The number of patients with decreased serum prostate-specific antigen level was significantly higher in the EstRadium therapy group than in the non-EstRadium therapy group (p=0.029). The combination of Ra-223 and EE, compared to Ra-223 alone, is an effective treatment option for bone mCRPC patients, in terms of PSA response.

Effect of Oral Contraceptive Pill and Metformin on Metabolic and Endocrine Parameters in Polycystic Ovarian Syndrome: A Prospective Interventional Study

Introduction: Polycystic Ovarian Syndrome (PCOS) is one of the most common endocrinopathies, affecting women of reproductive age group worldwide. There is no comprehensive data, regarding the outcome of various treatment modalities. Aim: To assess the effect of Oral Contraceptive Pills (OCP) and metformin on metabolic and endocrine parameters in PCOS. Materials and Methods: It was a prospective interventional study, done over a period of 12 months from January 2017 to January 2018 at the Outpatient Department (OPD) of Gynaecology and Obstetrics, Medical College, Kolkata. A total of 162 PCOS patients were recruited. The selected patients were divided into two groups A and B, based on the clinician’s assessment with respect to the patient profile. Group A received lifestyle intervention plus metformin (started at 500 mg / day and according to patient’s response and the clinical judgement titrated upto 2000 mg/day for 6 months) and group B received lifestyle intervention plus oral contraceptive pill. (fixed dose combination of ethinyl estradiol 50 micrograms and cyproterone acetate 2 milligrams per day for 6 months). The patients were assessed for metabolic parameters [Fasting Blood Sugar (FBS), Post-Prandial Blood Sugar (PPBS), Haemoglobin A1C (HbA1C), lipid profile] and endocrine parameters [testosterone, prolactin and Thyroid Stimulating Hormone (TSH)]. The Student t-test, Chisquare test and Analysis of Variance (ANOVA) test were used to compare the data. Results: A total of 162 patients were recruited for the present study with the mean age in group A was 23.75±1.7 and in group B was 22.40±1.6 years. The mean HbA1C levels of group A before the initiation of the treatment was found to be 7.51±0.89% which was reduced to 7.45±0.49% and 6.83±0.34% at the end of two months and six months respectively (p-value=0.001). In group B, serum testosterone was significantly reduced from 2.86±0.48 to 2.18±0.42 (p-value=0.0001), however the glycemic control worsened. Conclusion: OCPs and metformin do not significantly correct metabolic abnormalities associated with PCOS, although, gynecological symptoms are improved significantly. Comparatively, metformin helps in control of blood sugar levels but high BMI and deranged lipid profile remains unaltered by both metformin and OCP.

Efficacy of Oral Tranexamic Acid Versus Combined Oral Contraceptives for Heavy Menstrual Bleeding.

IntroductionHeavy menstrual bleeding (HMB) is characterized by high blood loss (>80 mL per cycle) at regular menstrual intervals. It can have an impact on a woman's bodily, mental, and/or material well-being. The etiology is varied and can be local, systemic, or iatrogenic. The occurrence of HMB is between 4% and 27%, depending on objective menstrual bleeding measurements and on high estimates based on subjective bleeding measures. This study was conducted to assess the efficacy of oral tranexamic acid versus combined oral contraceptive (COC) pills in the management of excessive menstrual bleeding.MethodologyA comparative study was conducted at the Obstetrics and Gynecology Department of Combined Military Hospital Peshawar, Pakistan, from October 2020 to March 2021. Women aged above 18 years who presented with heavy menstrual bleeding (HMB) were included in the study. The exclusion criteria included all women with contraindications to the use of tranexamic acid, such as lactating mothers, pregnancy, use of oral contraceptives or steroids, history of renal malfunction or stroke, family history of thromboembolic disease, and ovarian or endometrial carcinoma. Patients with diagnosed leiomyomas with a size between >1 and 10 cm were included in the study. Women were allocated randomly into group A who received oral tranexamic acid 3.9-4 g per day or group B who received oral COC pills containing a combination of ethinyl estradiol 30 μg and norgestrel 0.3 mg. The efficacy of treatment was considered successful if there was a mean reduction in menstrual blood loss that was significantly greater than the baseline values.ResultsThere were 178 patients in total, with 89 patients in each group. It was found that both oral tranexamic acid and combined oral contraceptives were equally effective in reducing the mean blood loss among patients and there was no statistical difference observed between the two groups. Upon stratification, it was found that both treatment groups were highly effective in younger age groups. Similarly, there was no significant difference in efficacy with respect to diabetes mellitus or hypertension. However, in individuals with leiomyomas, efficacy was significantly higher in patients who were in group B (combined oral contraceptives) (p = 0.004), and 46.1% of women in group A and 60.6% of women in group B did not experience any discomfort.ConclusionThe current study revealed that both oral tranexamic acid and COC pills were equally effective in reducing the mean blood loss among patients with HMB. It was further found that the efficacy of both therapies was significantly higher in younger age groups. The efficacy of therapy was significantly reduced with the increasing age of the patient. Moreover, it was found that patients with leiomyomas benefitted more significantly from COC pills. There were no severe adverse effects reported in the study. However, future researches can explore the long-term side effects of both therapies.In short, both therapies were comparable in terms of efficacy and safety. Heavy menstrual bleeding can negatively impact a woman, emotionally and physically. Therefore, it is encouraged that physicians use their expert judgment while prescribing either oral tranexamic acid or COC pills to patients with HMB.

Comparison of the Efficacy and Tolerability of Dienogest and Dienogest Plus Ethinylestradiol on Endometriosis Related-Pain

Objective: Endometriosis is a common gynecological condition that affects many women of reproductive age worldwide and is a major cause of pain and infertility. Treatment of endometriosis can be either surgical, aiming to restore normal anatomy by removing endometriotic lesions, or hormonal. Various medical treatments with different doses, formulations, delivery systems, and regimens have been tested. The main objective of this study was to compare the efficacy and tolerability of dienogest and dienogest plus ethinylestradiol on endometriosis-related pain. Additionally, the effects on endometrioma size were examined.Study Design: A total of 81 patients with clinically diagnosed endometrioma, who had chronic pelvic pain, dysmenorrhea, or deep dyspareunia between January 2015 and December 2018 were studied retrospectively. The patients were divided into two main groups: continuous oral dienogest (n=43) (Visanne®, 2 mg/day) and continuous oral dienogest plus ethinylestradiol (n=38) (Dienille®, 2 mg/0.03 mg/day). The intensity of pain symptoms was evaluated before therapy, then after 3 and 6 months of treatment using a 10-point numerical rating scale (0 = no pain and 10 = worst possible pain) (NRS) provided to the patients in advance.Results: The pain scores related to chronic pelvic pain decreased 36% for dienogest and 49% for dienogest plus ethinylestradiol (p&lt;0.05) and scores for dysmenorrhea decreased 38% and 44% respectively (p&lt;0.05) at 6 months, significantly lower than before treatment. At the 6-month follow-up, a 28% decrease in the pain scores related to deep dyspareunia in the dienogest group was statistically significant. Although the dienogest plus ethinylestradiol group also decreased by 20%, the difference was not significant. There was no significant difference in endometrioma size between the two groups at the 6-month follow-up (dienogest and dienogest plus ethinylestradiol; 24.2±17.5 mm vs. 27.5±19.1 mm, respectively; p=0.42).Conclusion: Upon analysis of our 6 months of clinical data, estrogen-progestin and a progestin alone seem to be of similar efficacy for the temporary treatment of endometriosis-related pain. The dienogest plus ethinylestradiol combination was slightly less effective on deep dyspareunia but was still well tolerated. Similarly, the two hormonal regimens posed no superiority over one another with regard to endometrioma size reduction.

Smoking while using contraceptives: Risk perception and behavioral intention to quit

Abstract Background Combining smoking with contraceptives containing ethinylestradiol increases the risk at several health issues, such as thrombosis, cardiovascular diseases and pulmonary embolism, especially when women are 35 years or older. It is important to inform women at an early stage and encourage them to quit smoking or change their contraceptive. The aim of this study is twofold. 1) using the Protection Motivation theory, we examine the predictors of the intention to quit smoking or change the currently used contraceptive method. 2) we provide insight into women's preferred ways to be informed and possible facilitators to change their behavior. Methods 68 Women, between 25 and 60 (mean age 30.6, sd 6.6; academic degree 78%), using the combination of smoking and ethinylestradiol containing contraceptives of a General Practice in Amsterdam, The Netherlands, filled in a questionnaire. Predictors were cigarette dependence (cds-5), perceived severity, vulnerability, response efficacy and self-efficacy. Outcome variables: intention to quit smoking or the current contraceptive. Results The average intention to quit smoking was higher (3,26 on a 5-point scale) than the average intention to quit the contraceptive method (2,47 on a 5-point scale). The predictors vulnerability, education level and reason for contraceptive use significantly predicted the intention to quit smoking (F(3, 65) = 40.22, p = .03), while self-efficacy and education level significantly predicted the intention to quit the contraceptive method. (F(2, 66) = 32.36, p =.02) Conclusions Risk perception stimulates women to quit smoking, while perceiving oneself capable of quitting or having alternatives is related to contraceptive change. A second wave of data is collected to enlarge the sample size. We add a qualitative study to get insight into strategies to alter women's behavior. This study will inform risk communicators and health care professionals, ultimately resulting in less women with this combination. Key messages Quitting smoking is potentially popular in a group of women with the risky combination of smoking with contraceptives containing ethinylestradiol. Risk perception stimulates women to quit smoking, while perceiving oneself capable of quitting or having alternatives is related to contraceptive change.

MON-255 Oral Contraceptive Pills Mask an Aggressive Crooke’s Cell Pituitary Adenoma

BackgroundCrooke’s cell tumors are rare and aggressive forms of pituitary adenomas. This variant of Cushing’s disease requires prompt diagnosis to avoid life-threatening complications. We report a unique case of Crooke’s cell tumor with longstanding history of irregular menstrual cycles, undiagnosed and later presented as acute unilateral ptosis and diplopia due to aggressive tumor invasion.Clinical Case23-year-old female presented to the ER with facial swelling, left eye droop and diplopia for 3 days. She had a past medical history of oligomenorrhea and hirsutism which was normalized by oral contraceptive pills (OCP)- a combination of ethinyl estradiol and drospirenone for the last 3 years. Years prior, workup of her oligomenorrhea showed normal androgenic profile with normal DHEA-S, testosterone and 17-OH progesterone. Current exam was also significant for elevated blood pressure 200/110mmHg, BMI 37, pigmented abdominal striae and terminal hair over her chin. Labs remarkable for hypokalemia K+ 2.7 mmol/L (3.5-5.3), elevated AM cortisol 51 mcg/dL (4-20), low TSH 0.152 mcUnit/mL (0.4-5.0), low IGF-1 170 ng/mL (222-566) and FSH 1.4 mUnit/mL (1.0-9.0), with normal prolactin 24.3 ng/mL (<0.5-25) and free T4 0.87ng/dL (0.8-1.8). MRI brain showed 2.8cm homogenous enhancing soft tissue mass involving the central skull base, sphenoid sinus, sella, suprasellar cistern, and parasellar regions; displacing the optic chiasm, and invading the cavernous sinuses bilaterally and orbital apices. Post trans-sphenoidal surgery (TSS) of the pituitary mass, her left eye ptosis and diplopia resolved. Post-op MRI showed subtotal resection of the extra-axial enhancing abnormality at the central skull base with extension to multiple other anatomic spaces. Pathology read consistent with aggressive Crooke’s cell adenoma, showing invasive biologic behavior without an elevated proliferation index with positive ACTH immunohistochemistry supportive of corticotroph cell adenoma. Post-op ACTH level 73 pg/mL (6-50) and cortisol 12.5 mcg/dL (4-20), while on dexamethasone. Repeat TSS was performed for residual adenoma. Cortisol remains elevated at 15.7mcg/dL despite high dose dexamethasone taper by the neurosurgery team for post-op development of right eye ptosis. She is currently awaiting proton beam radiation therapy.ConclusionCrooke’s cell tumors are an aggressive form of pituitary adenoma for which early diagnosis is crucial for its prognosis. Our case highlights the importance of maintaining a wide differential in evaluating young women with menstrual irregularities and to include screening for Cushing’s syndrome. Empiric treatment with OCPs can mask symptoms in the earlier course of Cushing’s disease as in our patient, causing recognition only after presentation with significant tumor growth. Earlier detection could have prevented adenoma invasion and potential neurological sequelae.

Bleeding Pattern and Management of Unexpected Bleeding/Spotting with an Extended Regimen of a Combination of Ethinylestradiol 20 mcg and Drospirenone 3 mg.

ObjectiveTo compare the bleeding pattern in women using ethinylestradiol 20 mcg/drospirenone 3 mg (EE 20 mcg/DRSP 3 mg) in a 24/4-day cyclic regimen with an extended regimen. Unexpected bleeding/spotting in the extended regimen group was managed by allowing a 4-day hormone-free interval (HFI).MethodsThis was a randomized, prospective, open-label, multicenter study. Participants (N = 348) were randomized to receive EE 20 mcg/DRSP 3 mg in either an extended regimen (EE/DRSPes group) or a 24/4-day cyclic regimen (EE/DRSP24/4 group) and followed for 168 days. In the EE/DRSPes group, a 4-day HFI was allowed whenever unexpected bleeding/spotting persisted for ≥7 consecutive days. The participants assessed their bleeding daily as “no bleeding,” “spotting,” or “light,” “moderate,” or “heavy” bleeding according to a predefined scale.ResultsEE/DRSPes group experienced fewer days of bleeding than those using a 24/4 cyclic regimen (P < 0.001). After 168 days, 57.5% of women in the EE/DRSPes group achieved complete amenorrhea (i.e., neither bleeding nor spotting) and 73.9% achieved “no bleeding” (i.e., no bleeding with or without spotting) during the final 28-day interval of the study period. Women in the extended group who instituted the 4-day HFI experienced a 94.1% rate of successful management of unexpected bleeding/spotting.ConclusionThe use of EE 20 mcg/DRSP 3 mg in an extended regimen resulted in high rates of amenorrhea and “no bleeding”. Unexpected bleeding/spotting in the EE/DRSPes group could be managed effectively with a 4-day HFI.Clinical Trial RegistrationInternational Standard Randomised Controlled Trial Number (ISRCTN57661673): http://www.controlled-trials.com/isrctn/pf/57661673.

A high resolution LC–MS targeted method for the concomitant analysis of 11 contraceptive progestins and 4 steroids

In the context of hormonal contraception and hormone replacement therapy (HRT), many women are exposed to exogenous hormones. Current use of hormonal contraception with combined ethinyl estradiol and different progestins bestows a breast cancer relative risk (RR) of 1.2- while combined HRT has a RR of 2. Although these exposures present an important public health issue, little is known about the effects of individual progestins on the breast and other tissues. Increasing availability of large scale biobanks, high throughput analyses and data management tools enable ever expanding, sophisticated population studies. In order to address the impact of distinct progestins on various health indicators, it is desirable to accurately quantify progestins in clinical samples.Here we have developed and validated a high resolution liquid chromatography mass spectrometry (LC–MS) targeted method for the simultaneous quantification of 11 synthetic progestins widely used in oral contraceptives, gestodene, levonorgestrel, etonogestrel, chlormadinone acetate, cyproterone acetate, drospirenone, desacetyl norgestimate, medroxyprogesterone acetate, norethindrone, dienogest, nomegestrol acetate, and 4 endogenous steroid hormones, progesterone, testosterone, androstenedione, and cortisol in blood samples. This highly specific quantitative analysis with high resolution Orbitrap technology detects and quantifies 15 compounds using their internal standard counterparts in a single 12 min LC–MS run. Sensitivity is attained by the use of the instrument in targeted selected ion monitoring mode. Lower limit of quantitation ranges from 2.4 pg/ml for drospirenone to 78.1 pg/ml for chlormadinone acetate. The method provides comprehensive progestin panel measurements with as little as 50 μl of murine or human plasma.

082 Nomegestrol Acetate/17beta-estradiol does not Negatively alter the Vascular Resistance of Clitoral Arteries

Recently, a monophasic combined oral contraceptive (COC) containing 1.5 mg 17-beta estradiol (E2) and 2.5 mg nomegestrol acetate (NOMAC) has been developed with a 24/4 regimen. While E2 is identical to the endogenous estrogen, NOMAC is a 19-nor progestogen derivative with no androgenic effects. NOMAC/E2 has demonstrated a good safety profile and less effects on cardiovascular risk, hemostatic, metabolic, and endocrine factors in comparison to COCs containing ethinyl estradiol in combination with levonorgestrel or drospirenone. Evidence suggests that NOMAC/E2 may be a good choice for preserving sexual health in women complaining about sexual side-effect of COCs. Clitoral color Doppler ultrasound (CDU) with assessment of the pulsatility index (PI), reflecting resistance to blood flow, has been proposed as an objective measurement of sexual functioning. Moreover, clitoral PI has been reported to be directly associated with cardiovascular risk factors and self-reported poor peripheral arousal during sexual activity. Our aim was to evaluate, in women consulting our Outpatient Clinic for contraceptive needs, the possible changes in clitoral hemodynamic parameters after 6 months treatment with NOMAC/E2 as compared with other COCs.

Information on the combined hormonal contraceptives (CHC) containing the dienogest + ethinyl estradiol combination (Jeanine®)

In this short communication, the editorial board publishes the information on safety of the combined hormonal contraceptive (CHC) Jeanine®, containing the fixed dose combination of dienogest and ethinyl estradiol. This information has been received from the Russian regulatory authority (Roszdravnadzor) and the manufacturer. According to a metaanalysis of four observational studies, women using the dienogest/ethinyl estradiol fixed dose combination had a higher risk of developing venous thromboembolism (VTE) as compared with women taking the CHCs containing the levonorgestrel/ ethinyl estradiol combination. The estimated risk of developing VTE in women taking the dienogest/ethinyl estradiol combination is 8-11 cases of VTE per 10,000 women per year, while in women taking the CHCs containing levonorgestrel, norethisterone or norgestimate the risk is 5-7 cases of VTE per 10,000 women per year. A patient information leaflet amendment is under consideration by the regulatory authorities. For now, however, hormonal contraceptives containing the dienogest/ethinyl estradiol combination accompanied with the previous version of the instruction are still available in pharmacies. Therefore, when prescribing the combined hormonal contraceptives with dienogest and ethinyl estradiol, the obstetrician-gynecologist should discuss these risks with the woman.

SUN-535 Impact of Route of Estrogen Administration on Bone Turnover Markers in Oligoamenorrheic Athletes and Mediators of these Effects

Transdermal, but not oral, estrogen replacement improves bone mineral density (BMD) in athletes with oligo-amenorrhea (OA). Our objective was to determine mechanisms that may explain the impact of route of estrogen administration on bone outcomes. Whereas IGF-1 is bone anabolic, sclerostin, preadipocyte factor-1 (Pref-1) and brain derived neurotropic factor (BDNF) inhibit bone formation, and an effect of estrogen on these factors has been demonstrated in other populations. However, few studies have examined the impact of route of estrogen administration on these factors in adolescents and young adults. Further, it is unclear how the route of estrogen administration impacts bioavailable testosterone, which in turn may impact bone outcomes in young oligo-amenorrheic women. 73 OA 14-25 years old received (i) a 17β-estradiol transdermal patch continuously with cyclic oral micronized progesterone (PATCH), (ii) a combined ethinyl estradiol and desogestrel pill (PILL), or (iii) no estrogen/progesterone (NONE) for 12-months. We evaluated fasting morning levels of a marker of bone formation [N-terminal propeptide of type 1 procollagen (P1NP)], a marker of bone resorption [N-telopeptide (NTX)], IGF-1, insulin-like growth factor binding protein 3 (IGFBP3), total testosterone, estradiol, sex hormone-binding globulin (SHBG), sclerostin, Pref-1, BDNF, calcium, 25(OH) vitamin D, and parathyroid hormone (PTH) at baseline and 12-months. Groups did not differ for age, weight, exercise activity or markers of bone formation at baseline. We have previously reported increases in areal BMD Z-scores at the spine and femoral neck in the PATCH compared to PILL and NONE groups (Ackerman et al: BJSM Oct. 2018). Over 12 months, between group analysis showed greatest decreases of P1NP in the PILL group (p=0.03) associated with a decrease in IGF-1 and IGF1/IGFBP-3 ratio (r=0.33, p≤0.05), and an increase in SHBG (r=-0.28;p=0.02). Within group analysis showed that sclerostin, Pref-1 and BDNF decreased in the PATCH group over 12 months (p=0.01, 0.01 and 0.04 respectively). PATCH group had the greatest increases in estradiol (p=0.0009), and estradiol increases were associated with increases in BMD. Groups did not differ for changes in NTX. Transdermal 17β-estradiol does not cause the decrease in IGF-1 and SHBG observed with oral ethinyl estradiol. It leads to decreases in sclerostin, Pref-1 and BDNF. These effects may mediate the beneficial effects of transdermal estrogen on bone in young women.

A New Year-Long Combination Hormonal Contraceptive

The U.S. Food and Drug Administration approved a new combination hormonal contraceptive in August 2018. Sold under the brand name Annovera, it is a combination of segesterone acetate and ethinyl estradiol, and it is the first multiuse vaginal contraceptive system that prevents ovulation for up to 13 menstrual cycles in a year. Although there are several combination hormonal contraceptives on the market, this is the first single system that can be repeatedly used for an entire year and does not require placement by a health care provider. This innovation gives women control over when to stop using the contraceptive, should they so desire. Annovera is stored at room temperature when not in use, allowing women living in uncontrolled-temperature climates to use one contraceptive method for an entire year.

Short article: Hormone therapy for severe gastrointestinal bleeding due to multiple angiodysplastic lesions.

This study aims to assess the efficacy of hormone therapy in patients with severe gastrointestinal bleeding due to multiple angiodysplastic lesions. Between May 2010 and July 2017, we included 12 consecutive patients with anaemia or recurrent bleeding due to angiodysplasia who had been started on hormone therapy. The therapy given was a combination of levonorgestrel (between 0.10 and 0.25 mg) and ethinylestradiol (between 0.02 and 0.05 mg). We determined the mean number of transfusions required in the 6 months before and after the start of the treatment, as well as the mean haemoglobin levels, number of admissions for anaemia due to gastrointestinal bleeding and length of hospital stay in these periods. The mean age of patients included was 77.83 years old and 75% were male. The follow-up period after treatment initiation was 6 months. Of the 12 patients included, only one stopped the treatment owing to it not being effective. Overall, 83.3% of the patients reported subjective improvement. Furthermore, we found significant differences comparing before and after starting treatment regarding the mean number of transfusions (7±4.8 vs. 3.4±4.6; P=0.005), the mean haemoglobin levels (9.5±1.2 vs. 10.8±2.6; P=0.034) and the mean number of admissions (1.6±1.6 vs. 0.2±0.4; P=0.024). On the contrary, differences between pretreatment and post-treatment length of hospital stay were not significant. Hormone therapy is a potentially useful therapeutic tool in patients with refractory bleeding and anaemia due to angiodysplasia.

Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial

ObjectiveNormal-weight oligo-amenorrhoeic athletes (OAA) are at risk for low bone mineral density (BMD). Data are lacking regarding the impact of oestrogen administration on bone outcomes in OAA. Our objective was...