Treatment continuation and satisfaction in women using combined oral contraception with nomegestrol acetate and oestradiol: a multicentre, prospective cohort study (BOLERO).

OBJECTIVE: The aim of the study was to examine treatment continuation and satisfaction over 1 year among women receiving nomegestrol acetate (NOMAC)/oestradiol (E2) combined oral contraception (COC) in real-world clinical practice. METHODS: The 17ß-Estradiol and Nomegestrol Acetate (BOLERO) Study is an observational, non-interventional, prospective, multicentre cohort study of premenopausal women (aged 18-50 years) who received prescription NOMAC/E2 (2.5 mg/1.5 mg) for contraception during routine clinical practice. Assessments were carried out at enrolment and at 3, 6 and 12 months. Probability of treatment continuation through 12 months (primary outcome) was examined using Kaplan-Meier survival analysis. Secondary outcomes included treatment satisfaction, menstrual cycle-related symptoms, libido and adverse events (AEs). RESULTS: Of 298 enrolled women, 292 were evaluable. The probability of NOMAC/E2 continuation through 12 months was 73.7% (95% confidence interval [CI] 68.0%, 78.5%). Satisfaction with NOMAC/E2 increased from 56.9% (37/65) of women at initial evaluation to 89.2% (58/65) of women at 12 months. Physician ratings at 12 months showed satisfactory to very satisfactory in 84.0% (168/200) of women. Libido was not affected. Menstrual cycle-related symptoms significantly declined from enrolment (6.04 ± 4.32) to 3 months (3.25 ± 3.05) and 12 months (2.62 ± 2.74; p < .0001). Treatment-related AEs were reported by 38.7% (113/292) of women. CONCLUSION: The real-world experience of women receiving NOMAC/E2 indicated very good treatment continuation, high satisfaction and significantly improved menstrual cycle-related symptoms.

Menopause and hormone replacement therapy: the 2017 Recommendations of the Italian Menopause Society.

Over the last decade, the risk benefits ratio of hormone replacement therapy (HRT) has been reevaluated mainly in tens of cardiovascular risk. Present Consensus Statement is largely inspired by the Global Consensus on Menopausal Hormone Therapy in 2013 and 2016 by leading global menopause societies (The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society). The aim of these recommendations is to provide a simple and updated reference on postmenopausal HRT. The term HRT typically includes estrogen replacement therapy (ERT) and estrogen-progestogen therapy (EPT). EPT can be sequential, when progestogen is added to ERT for 10-14 days a month, or continuous combined when progestogen is administered continuously every day along with a fixed amount of estrogen, In the everyday language, HRT includes also tibolone and the tissue-selective estrogen complex.

Does dienogest influence the inflammatory response of endometriotic cells? A systematic review.

OBJECTIVE AND DESIGN: A systematic review of all literature was done to assess the ability of the progestin dienogest (DNG) to influence the inflammatory response of endometriotic cells. MAIN OUTCOME MEASURES: In vitro and in vivo studies report an influence of DNG on the inflammatory response in eutopic or ectopic endometrial tissue (animal or human). RESULTS: After strict inclusion criteria were satisfied, 15 studies were identified that reported a DNG influence on the inflammatory response in endometrial tissue. These studies identified a modulation of prostaglandin (PG) production and metabolism (PGE2, PGE2 synthase, cyclo-oxygenase-2 and microsomal PGE synthase-1), pro-inflammatory cytokine and chemokine production [interleukin (IL)-1ß, IL-6, IL-8, tumor necrosis factor-α, monocyte chemoattractant protein-1 and stromal cell-derived factor-1], growth factor biosynthesis (vascular endothelial growth factor and nerve growth factor) and signaling kinases, responsible for the control of inflammation. Evidence supports a progesterone receptor-mediated inhibition of the inflammatory response in PR-expressing epithelial cells. It also indicated that DNG inhibited the inflammatory response in stromal cells, however, whether this was via a PR-mediated mechanism is not clear. CONCLUSIONS: DNG has a significant effect on the inflammatory microenvironment of endometriotic lesions that may contribute to its clinical efficacy. A better understanding of the specific anti-inflammatory activity of DNG and whether this contributes to its clinical efficacy can help develop treatments that focus on the inhibition of inflammation while minimizing hormonal modulation.

The Association between Endometriomas and Ovarian Cancer: Preventive Effect of Inhibiting Ovulation and Menstruation during Reproductive Life.

Although endometriosis frequently involves multiple sites in the pelvis, malignancies associated with this disease are mostly confined to the ovaries, evolving from an endometrioma. Endometriomas present a 2-3-fold increased risk of transformation in clear-cell, endometrioid, and possibly low-grade serous ovarian cancers, but not in mucinous ovarian cancers. These last cancers are, in some aspects, different from the other epithelial ovarian cancers, as they do not appear to be decreased by the inhibition of ovulation and menstruation. The step by step process of transformation from typical endometrioma, through atypical endometrioma, finally to ovarian cancer seems mainly related to oxidative stress, inflammation, hyperestrogenism, and specific molecular alterations. Particularly, activation of oncogenic KRAS and PI3K pathways and inactivation of tumor suppressor genes PTEN and ARID1A are suggested as major pathogenic mechanisms for endometriosis associated clear-cell and endometrioid ovarian cancer. Both the risk for endometriomas and their associated ovarian cancers seems to be highly and similarly decreased by the inhibition of ovulation and retrograde menstruation, suggesting a common pathogenetic mechanism and common possible preventive strategies during reproductive life.

Modification of body composition and metabolism during oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol.

AIM: To observe the influence on metabolism and body composition of two oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol (EE). STUDY DESIGN: Women on hormonal contraception with estradiol valerate (E2V)/dienogest (DNG) in a quadriphasic regimen (n = 16) or 30 µg EE/2 mg chlormadinone acetate (CMA) (n = 16) in a monophasic regimen were evaluated at the third cycle for modifications in lipoproteins, apoproteins and homeostatic model assessment for insulin resistance (HOMA-IR), and at the sixth cycle for body composition and the markers of bone turnover osteocalcin and C-telopeptide X. RESULTS: During E2V/DNG lipoprotein, apoproteins and HOMA-IR remained stable. During EE/CMA, total-cholesterol (p = 0.003), high-density lipoprotein (HDL)-cholesterol (p = 0.001), triglycerides (p = 0.003) Apoprotein-A1 (Apo-A1; p = 0.001) and Apo B (p = 0.04) increased, low-density lipoprotein/HDL (p = 0.039) decreased and total-cholesterol/HDL and Apoprotein-B/Apo-A1 ratio did not vary. HOMA-IR slightly increased from 1.33 ± 0.87 to 1.95 ± 0.88 (p = 0.005). There was a reduction of markers of bone metabolism in both groups with no modification of body composition. CONCLUSIONS: Administration of E2V/DNG does not influence lipid and glucose metabolism, while mixed effect are exerted by EE/CMA. Both preparations reduce bone metabolism without influencing short-term effect on body composition.

Multinational, multicentre, randomised, open-label study evaluating the impact of a 91-day extended regimen combined oral contraceptive, compared with two 28-day traditional combined oral contraceptives, on haemostatic parameters in healthy women.

OBJECTIVES: To evaluate the impact of a 91-day extended regimen combined oral contraceptive (150 µg levonorgestrel [LNG]/30 µg ethinylestradiol [EE] for 84 days, followed by 10 µg EE for seven days [Treatment 1]) compared with two traditional 21/7 regimens (21 days 150 µg LNG/30 µg EE [Treatment 2] or 150 µg desogestrel [DSG]/30 µg EE [Treatment 3], both with seven days' hormone free), on several coagulation factors and thrombin formation markers. METHODS: Randomised, open-label, parallel-group comparative study involving healthy women (18-40 years). The primary endpoint was change from baseline in prothrombin fragment 1 + 2 (F1 + 2) levels over six months. RESULTS: A total of 187 subjects were included in the primary analysis. In all groups, mean F1 + 2 values were elevated after six months of treatment. Changes were comparable between Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L, respectively) but noticeably larger after Treatment 3 (least squares mean change: 592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95% confidence interval [- 18.3 pmol/L] > - 130 pmol/L). CONCLUSIONS: The LNG/EE regimens had similar effects on F1 + 2. Noninferiority was demonstrated between extended regimen LNG/EE and DSG/EE.

Effects of the insulin sensitizer pioglitazone on menstrual irregularity, insulin resistance and hyperandrogenism in young women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common endocrine cause of menstrual irregularities, hirsutism and acne. Women with PCOS present elevated plasma insulin levels, both fasting and after a glucose load, as an indirect evidence of insulin resistance. PCOS women may also present hypertension, low levels of HDL cholesterol, hypertriglyceridemia, visceral obesity and a higher level of CRP and fibrinogen that can predict an atherosclerotic risk. METHODS: This study was carried out on 15 young women with PCOS selected according to the 2003 diagnostic criteria of The Rotterdam Consensus Statement and 15 Control women. PCOS women were treated with pioglitazone 30 mg/day and at the beginning and after 6 months of treatment were evaluated: menstrual cycle trend, hirsutism and acne, total cholesterolemia and HDL, triglyceridemia, fibrinogenemia, C-reactive protein, oral glucose tolerance test, glycated hemoglobin, FSH, LH, 17OH-progesterone, 17ß-estradiol, free and total testosterone, SHBG, DHEA-S, Δ4-androstenedione and adiponectin. RESULTS AND DISCUSSION: Treatment with pioglitazone improves the irregularities of menses and hirsutism. Six months of treatment modify other parameters linked with a higher risk of type 2 diabetes mellitus and cardiovascular diseases: adiponectin increased with reduction of insulin resistance while fibrinogen and CRP levels decreased.

Age-specific reference values for serum FSH and estradiol levels throughout the reproductive period.

High serum day 3 FSH levels are associated with poor ovarian reserve and reduced fertility, but the interpretation of FSH values according to age is still not univocal. The purpose of this study was to determine age-dependent reference values in women with regular menstrual cycles and FSH as a guide for specialists. The study was performed at the Department of Mother-Infant of a University-based tertiary care centre. One-hundred ninety-two healthy normal menstruating women were recruited for the study. All patients attended the department on menstrual cycle day 3 for a blood sample for FSH and estradiol determination. A linear relationship between FSH or estradiol serum levels and age was observed. The FSH level increased by 0.11 IU for every year of age (1 IU for every 9 years of age). The values of FSH and estradiol corresponding to the 5th, 25th, 50th, 75th, 95th centiles for any specific age have been calculated. Serum FSH levels need to be interpreted according to age-dependent reference values. Serum FSH levels on 95th centile for any age may represent a warning sign for reduced ovarian reserve.

Intensity of menstrual pain and estimated angle of uterine flexion.

OBJECTIVE: To assess the impact of ultrasound-estimated uterus position on the intensity of pelvic pain. DESIGN: Descriptive analytical study. SETTING: Tertiary university gynecology unit. POPULATION: 181 consecutive patients with pelvic pain. METHODS: Each woman underwent physical examination, transvaginal sonography and filled self-administered questionnaires on pain using a 10-cm visual analog scale (VAS). MAIN OUTCOME MEASURES: Visual analog scale score of menstrual pain, intermenstrual pain and dyspareunia was related to uterine version (ante- or retroversion) and the angle of uterine flexion (actual angle between cervix and uterine body) evaluated by transvaginal sonography. RESULTS: Estimated uterine version was not associated with the intensity of any type of pain. The estimated angle of flexion was higher in retroverted than in anteverted uteri (182.3° ± 50.3° vs. 142.3° ± 24.2°, p < 0.0001). Intensity of menstrual pain was lowest with flexion between 150° and 210° (4.9 ± 3.1) (p = 0.002), intermediate with flexion <150° (6.3 ± 2.8) and highest with flexion ≥210° (7.9 ± 2.3). Severe menstrual pain was more prevalent with flexion ≥210° (77.7%) than between 150° and 210° (31.4%; p = 0.0008) or <150° (45.2%; p = 0.005). The intensity of intermenstrual pain and dyspareunia were not associated with the angle of flexion. In multiple regression analysis, the angle of flexion was independently related only to the intensity of menstrual pain (r = 0.272; p = 0.002). CONCLUSIONS: In women with pelvic pain, ultrasound-estimated uterine flexion represents an independent risk for intense menstrual pain.

Pharmacokinetic evaluation of desogestrel as a female contraceptive.

INTRODUCTION: Desogestrel (DSG) is a third-generation 19-nortestosterone derivative progestogen. It is contained in many oral contraceptive preparations, both combined (COCs) to ethinyl-estradiol (EE) or alone in a progestin-only pill (POP). Its principal metabolite (etonogestrel, ETN) is the only progestin used for intravaginal combined contraception and one of the most used for subdermal hormonal contraception. AREAS COVERED: This is a review of the available data on the pharmacokinetics of DSG and ETN in hormonal contraception. The material included was searched and obtained via Medline, PubMed, and EMBASE up to July 2013 using the search terms 'pharmacokinetics, metabolism' in combination with 'desogestrel, etonogestrel, and progestins.' EXPERT OPINION: DSG and its metabolite ETN are very suitable molecules for use in hormonal contraception. For the oral use the molecule used is DSG, while for parenteral routes (intravaginal, subdermal) its metabolite ETN is the compound of choice. In both cases (oral and parenteral) the active molecule in the organism is the latter (ETN), due to the rapid in vivo metabolism of oral DSG. The contraceptive efficacy and tolerability of all the formulations present on the market (mono/multiphasic EE/DSG COCs, DSG POP, EE/ETN vaginal ring, ETN implant) are reassuring, permitting a long-term use. The estrogenic component increases the contraindications, forcing the prescription to the safer only-progestin preparations, DSG POP or ETN implant.

Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

Modification of 24-h ambulatory blood pressure and heart rate during contraception with the vaginal ring: a prospective study.

BACKGROUND: Hypertension is recognized as a major risk factor for coronary, cerebral and renal vascular disease. Hormonal methods of contraception may increase the risk for cardiovascular events. We evaluated whether the combined hormonal contraceptive vaginal ring that releases 15-mcg ethinylestradiol and 120 mcg of etonogestrel each day influences 24-h ambulatory blood pressure. STUDY DESIGN: At baseline, ambulatory blood pressure was automatically monitored every 30 min for 41 h in 18 normotensive healthy women during their follicular phase (Days 3-6). Each subject was immediately treated with the vaginal ring for six cycles. Monitoring of ambulatory blood pressure was repeated in the last days of the sixth cycle of treatment. RESULTS: During the vaginal ring, a significant increase was observed for 24-h diastolic (2.75±5.13 mmHg; p=.03) and mean (2.69±5.35 mmHg; p=.048) blood pressure and for daytime diastolic (3.04±6.36 mmHg; p=.05) blood pressure. No variation was found in nighttime blood pressure. Heart rate increased in the 24-h period (3.39±5.85 beats/min; p=.025) and in the daytime (3.38±6.25 beats/min; p=.034) measurements. CONCLUSIONS: In normotensive women, the vaginal ring slightly increases 24-h blood pressure and heart rate. The underlying mechanisms and the clinical impact of these slight modifications require further evaluation.

Prediction of age at menopause from assessment of ovarian reserve may be improved by using body mass index and smoking status.

OBJECTIVE: Menopause is the consequence of exhaustion of the ovarian follicular pool. AMH, an indirect hormonal marker of ovarian reserve, has been recently proposed as a predictor for age at menopause. Since BMI and smoking status are relevant independent factors associated with age at menopause we evaluated whether a model including all three of these variables could improve AMH-based prediction of age at menopause. METHODS: In the present cohort study, participants were 375 eumenorrheic women aged 19-44 years and a sample of 2,635 Italian menopausal women. AMH values were obtained from the eumenorrheic women. RESULTS: Regression analysis of the AMH data showed that a quadratic function of age provided a good description of these data plotted on a logarithmic scale, with a distribution of residual deviates that was not normal but showed significant left-skewness. Under the hypothesis that menopause can be predicted by AMH dropping below a critical threshold, a model predicting menopausal age was constructed from the AMH regression model and applied to the data on menopause. With the AMH threshold dependent on the covariates BMI and smoking status, the effects of these covariates were shown to be highly significant. CONCLUSIONS: In the present study we confirmed the good level of conformity between the distributions of observed and AMH-predicted ages at menopause, and showed that using BMI and smoking status as additional variables improves AMH-based prediction of age at menopause.

Polymorphisms in gonadotropin and gonadotropin receptor genes as markers of ovarian reserve and response in in vitro fertilization.

Since gonadotropins are the fundamental hormones that control ovarian activity, genetic polymorphisms may alter gonadal responsiveness to glycoproteins; hence they are important regulators of hormone activity at the target level. The establishment of the pool of primordial follicles takes place during fetal life and is mainly under genetic control. Consequently, single nucleotide polymorphisms (SNPs) in gonadotropins and their receptors do not seem to be associated with any significant modification in the endowment of nongrowing follicles in the ovary. Indeed, the age at menopause, a biological characteristic strongly related to ovarian reserve, as well as markers of functional ovarian reserve such as anti-Müllerian hormone and antral follicle count, are not different in women with different genetic variants. Conversely, some polymorphisms in FSH receptor (FSHR) seem to be associated with modifications in ovarian activity. In particular, studies suggest that the Ser680 genotype for FSHR is a factor of relative resistance to FSH stimulation resulting in slightly higher FSH serum levels, thus leading to a prolonged duration of the menstrual cycle. Moreover, some FSHR gene polymorphisms show a positive association with ovarian response to exogenous gonadotropin administration, hence exhibiting some potential for a pharmacogenetic estimation of the FSH dosage in controlled ovarian stimulation. The study of SNPs of the FSHR gene is an interesting field of research that could provide us with new information about the way each woman responds to exogenous gonadotropin administration during ovulation induction.

Individualization of the FSH starting dose in IVF/ICSI cycles using the antral follicle count.

BACKGROUND: The FSH starting dose is usually chosen according to women's age, anamnesis, clinical criteria and markers of ovarian reserve. Currently used markers include antral follicle count (AFC), which is considered to have a very high performance in predicting ovarian response to FSH. The objective of the present study to elaborate a nomogram based on AFC for the calculation of the appropriate FSH starting dose in IVF cycles. METHODS: This is a retrospective study performed at the Mother-Infant Department of Modena University Hospital. IVF patients (n=505) were subjected to blood sampling and transvaginal ultrasound for measurement of serum day3 FSH, estradiol and AFC. The variables predictive of the number of retrieved oocytes were assessed by backwards stepwise multiple regression. The variables reaching the statistical significance were then used in the calculation for the final predictive model. RESULTS: A model based on age, AFC and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting dose lower than 225 IU in 50.2% and 18.1% of patients younger and older than 35 years, respectively. CONCLUSIONS: The daily FSH dose may be calculated on the basis of age and two markers of ovarian reserve, namely AFC and FSH, with the last two variables being the most significant predictors. The nomogram seems easily applicable during the daily clinical practice.

Combined oral contraceptive containing drospirenone does not modify 24-h ambulatory blood pressure but increases heart rate in healthy young women: prospective study.

BACKGROUND: Hypertension is a primary cardiovascular risk factor. Oral contraceptives (OCs) may increase blood pressure and cardiovascular events. We evaluated whether an OC containing ethynylestradiol (EE) in association with the spironolactone-derived progestin drospirenone (DRSP) influences 24-h ambulatory blood pressure of normotensive women. STUDY DESIGN: Twenty-four-hour blood pressure was measured every 30 min by an ambulatory blood pressure device in 18 normotensive healthy women prior to and after 6 months of use of an OC containing 30 mcg EE and 3 mg DRSP. RESULTS: OC induced no modification in 24-h, nighttime and daytime blood pressure. Heart rate increased about 4 beats/min in the 24-h (p<.05) and daytime (p<.02) measurements. CONCLUSIONS: In normotensive women, an OC containing 30 mcg EE plus 3 mg DRSP does not modify blood pressure, and significantly increases 24-h and daytime heart rate. These data suggest a neutral effect on hypertension-associated cardiovascular risk and point out an unreported effect on heart rate of which cause and effect require further evaluation.

Intermenstrual pelvic pain, quality of life and mood.

BACKGROUND/AIMS: To investigate the independent importance of different types of pelvic pain on quality of life and depressive symptoms. METHODS: A cross-sectional study was performed on patients with pelvic pain. A 10-cm visual-analogue scale (VAS) was used to investigate intensity of intermenstrual pelvic pain, dysmenorrhea or deep dyspareunia. The SF-36 form and the Zung Self-Rating Scale for Depression (SDS) were used to investigate quality of life and depressive symptoms, respectively. RESULTS: The final study group consisted of 248 patients, 175/248 (70.6%) with intermenstrual pelvic pain, 46/248 (18.5%) with dysmenorrhea and 27/248 (10.9%) with deep dyspareunia associated or not with dysmenorrhea. Mean VAS score for dysmenorrhea was higher than that for deep dyspareunia (p < 0.003) and intermenstrual pelvic pain (p < 0.0001). Women with intermenstrual pelvic pain had the worst SF-36 (p < 0.0001) and SDS (p < 0.002) scores. SF-36 was independently and inversely related to intermenstrual pelvic pain (CR -1.522; 95% CI -2.188 to -0.856; p < 0.0001), and less strongly to dysmenorrhea (CR -0.729; 95% CI -1.487 to 0.030; p = 0.06). Indeed, only the physical component summary of SF-36 was independently related to dysmenorrhea (CR -0.956; 95% CI -1.783 to -0.129; p = 0.024). The SDS score was independently related only to intermenstrual pelvic pain (CR 0.573; 95% CI 0.241-0.904; p = 0.0008). CONCLUSIONS: Patients with intermenstrual pelvic pain have the worst SF-36 and SDS scores. Intermenstrual pelvic pain seems to be more strongly associated with a reduced quality of life and depressive mood.

Prevalence of menstrual pain in young women: what is dysmenorrhea?

OBJECTIVES: This study aimed to determine the frequency of dysmenorrhea, as identified by different definitions, in a population of young women, and to investigate factors associated with this complaint. MATERIALS AND METHODS: A final group of 408 young women completed a self-assessment questionnaire. This was a cross-sectional analytical study. RESULTS: Menstrual pain was reported by 84.1% of women, with 43.1% reporting that pain occurred during every period, and 41% reporting that pain occurred during some periods. Women with menstrual pain had an earlier menarche (P = 0.0002) and a longer menstrual flow (P = 0.006), and this group was characterized as having a higher prevalence of smokers (P = 0.031) and a lower prevalence of hormonal contraception users (P = 0.015). Pain intensity was correlated (r = 0.302, P < 0.0001) positively with menstrual flow length (CR = 0.336), history of abortions (CR = 3.640), and gynecological pathologies (CR = 0.948), and negatively with age at menarche (CR = -0.225), use of hormonal contraception (CR = -0.787), and history of gynecological surgery (CR = -2.115). Considering the parameters of menstrual pain, a need for medication, and inability to function normally (absenteeism from study or social activities) alone or together, the prevalence of dysmenorrhea is 84.1% when considering only menstrual pain, 55.2% when considering the association between menstrual pain and need for medication, 31.9% when considering the association between menstrual pain and absenteeism, and 25.3% when considering the association between menstrual pain, need for medication, and absenteeism (P < 0.0001). The probability of having more severe dysmenorrhea is directly related to pain intensity as measured by a visual analog scale, but does not coincide with it. CONCLUSION: Menstrual pain is a very common problem, but the need for medication and the inability to function normally occurs less frequently. Nevertheless, at least one in four women experiences distressing menstrual pain characterized by a need for medication and absenteeism from study or social activities.

Normal serum anti-Müllerian hormone levels in the general female population and the relationship with reproductive history.

OBJECTIVE: Anti-Müllerian hormone (AMH) has been evaluated by several groups as a potential novel clinical marker of ovarian reserve. Considering the wide use of AMH measurement in daily clinical practice and the large number of conditions in which it may be used, it is essential to establish reference values in the healthy female population. In this study we aim to calculate the age-by-age normal values of circulating AMH. In addition, we report on AMH levels in women according to BMI, smoking status and reproductive history. STUDY DESIGN: The study was performed at the Institute of Obstetrics and Gynecology, University of Modena, between January 2008 and December 2010. A total of 416 healthy women (aged 18-51) were recruited and serum AMH levels were measured for all of them. The centiles of AMH distribution were estimated with the CG-LMS method. The relationship between AMH levels and the womens' characteristics such as BMI, smoking status and reproductive history was analysed by using the uni- and multi-variable regression analysis and the Chi-square test. RESULTS: Serum AMH concentrations show a progressive decline with female ageing. Age-related nomograms for the 5th, 25th, 50th, 75th, and 95th percentiles of AMH were produced. Mean AMH concentrations were not modified by smoking habit and BMI and were independent of parity of the women. CONCLUSION: In the present study, we established age-specific reference values for circulating AMH levels in the eumenorrheic female population. AMH measurement produces new information on ovarian pathophysiology and ovarian reserve and the establishment of reference values for AMH is the first step for a correct interpretation of the assay.

Possibilities and limits of ovarian reserve testing in ART.

Markers of ovarian reserve are associated with ovarian aging as they decline with chronologic age, and hence may predict stages of reproductive aging including the menopause transition. Assessment of ovarian reserve include measurement of serum follicle stimulating hormone (FSH), anti-M�llerian hormone (AMH), and inhibin-B. Ultrasound determination of antral follicle count (AFC), ovarian vascularity and ovarian volume also can have a role. The clomiphene citrate challenge test (CCCT), exogenous FSH ovarian reserve test (EFORT), and GnRH-agonist stimulation test (GAST) are dynamic methods that have been used in the past to assess ovarian reserve. In infertile women, ovarian reserve markers can be used to predict low and high oocyte yield and treatment failure in women undergoing in vitro fertilization. However the markers may have limitations when an in depth analysis of their accuracy, cost, convenience, and utility is performed. As ovarian reserve markers may permit the identification of both the extremes of ovarian stimulation, a possible role for their measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in the ovarian reserve testing before initiation of an IVF cycle and whether the ovarian reserve markers-determined strategy of ovarian stimulation for assisted conception may be associated to improved live birth rate.