Oestrogens in oral contraception: considerations for tailoring prescription to women's needs.

BACKGROUND: The oestrogenic component of combined oral contraceptives (COCs) has changed over years with the aim of reducing oestrogen-related side effects and risks, whilst maintaining oestrogen beneficial effects, particularly on cycle control. PURPOSE: To describe the pharmacological profiles of different oestrogens commonly used in COCs to provide insights on contraceptive prescription tailored to women's needs. RESULTS: All COCs ensure a high contraceptive efficacy. COCs containing the natural oestrogens oestradiol (E2), oestradiol valerate (E2V) and estetrol (E4) have limited impact on liver metabolism, lipid and carbohydrate metabolism, haemostasis and sex hormone binding globulin levels, compared with ethinylestradiol (EE). COCs with E2 and E2V appear also to entail a lower elevation of the risk of venous thromboembolism vs. EE-containing pills. No epidemiological data are available for E4-COC. E2- and E2V-containing COCs seem to exert a less stabilising oestrogenic effect on the endometrium compared with EE-COCs. The E4-COC results in a predictable bleeding pattern with a high rate of scheduled bleeding and minimal unscheduled bleeding per cycle. Based on in vitro and in vivo animal data, E4 seems to be associated with a lower effect on cell breast proliferation. CONCLUSION: Today various COCs contain different oestrogens. Prescribers must be familiar with the different properties of each oestrogen for a tailored contraceptive recommendation, considering their safety and contraceptive efficacy, as well as women's needs and preferences.

For contraceptive pills physicians can choose among different oestrogens, besides many progestins. Natural oestrogens have less metabolic impact vs EE, while EE and E4 seem to provide a better cycle control. Knowing the different oestrogen characteristics is crucial for adjusting pill prescription to women's needs and desires.

Is the multinational, surveillance PRO-E2 study informative for all countries? The Italian data on VTE and contraceptive effectiveness.

PURPOSE: To evaluate whether the thromboembolic risk and contraceptive effectiveness of NOMAC-E2 observed in the PRO-E2 study can be extended to each participating country, as lifestyle, cardiovascular risk factors and prescribing habits may differ geographically. This analysis was performed on the PRO-E2 Italian subpopulation, where smoking habit and women over 35 years were more prevalent compared with the overall study population. MATERIALS AND METHODS: Data from NOMAC-E2 or levonorgestrel-containing COCs (COCLNG) new users were descriptively analysed. Incidence rates of thrombosis (events/10,000 women-years [WY]) and the Pearl Index (pregnancies/100 WY) were calculated. RESULTS: Overall, 11,179 NOMAC-E2 and 8,504 COCLNG users were followed up to 2 years (34,869 WY). The NOMAC-E2 cohort included more women over 35 vs. COCLNG (37.7% vs. 31.8%; p = 0.001). A comparable low risk of combined deep venous thrombosis of lower extremities (DVT) and pulmonary embolism (PE) was observed in NOMAC-E2 (1.7/10,000 WY; 95% CI: 0.21-6.2) and COCLNG users (6.6/10,000 WY; 95% CI: 2.4-14.4). Similar results were obtained by considering all thromboembolic events (VTE). Unintended pregnancies did not differ between NOMAC-E2 (0.12/100 WY; 95% CI: 0.06-0.21) and COCLNG (0.15/100 WY; 95% CI: 0.08-0.26) cohorts. CONCLUSION: Despite the higher age and tobacco use, findings from the Italian subpopulation were broadly consistent with overall PRO-E2 results, confirming a similar low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 and COCLNG. SHORT CONDENSATION: This subgroup analysis of the PRO-E2 study provides comprehensive epidemiological data on the use of combined oral contraceptives in a large Italian cohort, with a higher prevalence of women over 35 years and smokers. The study confirms the low thromboembolic risk and high contraceptive effectiveness of NOMAC-E2 pill.

NOMAC-E2 shows a better contraceptive effectiveness than LNG combined oral contraceptives in women under 25: real-world PRO-E2 study.

Objective: To investigate unintended pregnancy and changes in mood, acne, and weight in NOMAC-E2 vs levonorgestrel-containing COC (COCLNG) users under 25 years.Methods: In this large, observational study, new users (first-ever users of an eligible COC or restarting with the same or a new eligible COC after a break of at least 2 months) of NOMAC-E2 and COCLNG were recruited in 12 countries in Europe, Australia, and Latin America and followed up via questionnaires for up to 2 years. Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 women-years). Crude (HRcrude) and adjusted hazard ratios (HRadj) were calculated. Mood and acne changes were defined as change of score from baseline. Weight change was defined as percent change of body weight.Results: Overall, 12,829 NOMAC-E2 users and 17,095 COCLNG users under 25 were followed-up. The risk of unintended pregnancy was statistically significantly lower in the NOMAC-E2 cohort; confirmed events: 30 NOMAC-E2 (PI 0.24; 95% CI, 0.16-0.35) vs 94 COCLNG (PI 0.51; 95% CI, 0.41-0.62). The HRcrude for unintended pregnancy comparing NOMAC-E2 to COCLNG was 0.47 (95% CI, 0.31-0.71) and the HRadj was 0.52 (95% CI, 0.34-0.78). No differential effect on acne, mood, and weight was observed between cohorts.Conclusions: NOMAC-E2 shows a significantly better contraceptive effectiveness in young women and has no differential effect on acne, mood, and weight compared to COCLNG.

NOMAC-E2 compares to LNG combined oral contraceptives in women over forty: real-world PRO-E2 study.

OBJECTIVE: To investigate safety and effectiveness of NOMAC-E2 and levonorgestrel-containing COCs (COCLNG) in users over 40. METHODS: In this large, observational study, new users1 of NOMAC-E2 and COCLNG were recruited in Europe, Australia, and Latin America and followed-up via questionnaires. Incidence of venous thromboembolism (VTE) was expressed as incidence rate (IR; events/104 women-years [WY]). Unintended pregnancy was expressed by the Pearl Index (PI; contraceptive failures/100 WY). Mood and weight changes were defined as mean changes in mood score and percentage of body weight. RESULTS: Overall, 7,762 NOMAC-E2 and 6,059 COCLNG users over 40 were followed-up. NOMAC-E2 showed no increased VTE risk compared to COCLNG; confirmed events: 5 NOMAC-E2 (IR 5.9; 95% CI, 1.9-13.7) vs 4 COCLNG (IR 5.9; 95% CI, 1.6-15.1). Unintended pregnancy did not differ substantially between cohorts; confirmed events: 4 NOMAC-E2 (PI 0.05; 95% CI, 0.01-0.13) vs 5 COCLNG (PI 0.08; 95% CI, 0.03-0.18). No differential effect on mood and weight was observed between cohorts. CONCLUSIONS: NOMAC-E2 can be considered a valid alternative to COCLNG in perimenopausal women.

Estetrol: A New Choice for Contraception.

Estetrol (E4) is a natural estrogenic steroid that is normally produced by human fetal liver. Recent research has demonstrated that it is a potent, orally bioavailable, natural selective estrogen receptor modulator; it has a moderate affinity for both human estrogen receptor alpha (ERα) and ERß, with a preference for ERα. Clinical studies have demonstrated possible use as an estrogen in combined oral contraceptives (COC). COCs containing E4 and drospirenone (DRSP) showed a high acceptability, tolerability, and user satisfaction also when compared to COCs containing ethinylestradiol (EE). E4/DRSP effectively inhibits ovulation, with a similar effect on endometrium thickness than that of EE-containing COCs. Low doses (15 mg) of E4 with DRSP (3 mg) showed promising results in term of bleeding pattern and cycle control, also when compared to other COCs containing synthetic estrogens. Moreover, the association has limited effects on serum lipids, liver, SHBG levels, and carbohydrate metabolism. This combination also could drive a lower risk of venous thromboembolism than EE-containing COCs. In this review, we will summarize the actual knowledge about the new E4-containing contraceptive. Further large-scale studies in the full target population are needed to provide more insights into the cardiovascular safety profile and user satisfaction of E4/DRSP.

Characterization of a novel mutation V136L in bone morphogenetic protein 15 identified in a woman affected by POI.

BACKGROUND: Premature ovarian insufficiency (POI) is an ovarian defect characterized by primary or secondary amenorrhea, hypergonadotropism and hypoestrogenism which occurs before the age of 40 years with a major genetic component. In this study we performed clinical evaluation and genetic analysis of a group of 18 patients with POI. The study involved 18 consecutive women with POI. Karyotiping and genetic analysis for research of mutations in GDF9 (Growth Differentation Factor 9) and BMP15 (Bone morphogentic protein 15) genes and FMR1 (Fragile X Mental Retardation 1) premutation were carried out. In vitro functional study of the novel BMP15 mutation was performed using COV434 (Human ovarian granulosa tumour cells 434) cells of ovarian granulosa, which consistently express BMP responsive element, and luciferase reporter assay. RESULTS: Three patients (17%) had a family history of POI. Ten patients (56%) had a family history of autoimmune diseases and nine patients (50%) showed a personal history of one or more autoimmune diseases. Of patients for whom morphological assessment was available, almost half (44%) had poor follicle assets or small ovaries's size at pelvic US. Two patients (13%) showed reduced bone density at DEXA (Dual Energy X-ray Absorptiometry). All the women had normal female kariotype and no mutations in the GDF-9 gene or FMR1 premutations were found. A novel heterozygous mutation c.406G > C (V136L) of BMP15 gene was identified in one patient. After transfection in COV434 cells, BMP15 variant showed a significantly reduced luciferase activity compared to wild type. CONCLUSIONS: POI is a multifactorial disease with several health implications. Autoimmunity and genetics represent the most common aetiology. We identified and characterized a novel BMP15 mutation, providing an additional elucidation of molecular basis of this complex disorder.

Estro-progestin Contraceptives and Risk of Cervical Cancer: A Debated Issue.

Steroid contraceptive hormones may promote human papilloma virus (HPV) - DNA integration into the host genome, may bind to specific HPV-DNA sequences within transcriptional regulatory regions, and may modulate cell apoptosis. Most epidemiological studies, reported in this narrative review, have shown that oral contraception is associated with a 1.5-3.3-fold higher relative risk of cervical carcer, but only in users for >5 years and especially in HPV-positive women. The relative risk declines with increasing time since last use and is not different from that of never users after >10 years. Ten-year oral contraceptive use from the age of 20 years is associated with an increase in the cumulative incidence of invasive cervical cancer at the age of 50 years of approximately 1 case per 1,000. Oral contraception has a very small negative impact on the absolute risk of cancer of the uterine cervix.

Hormonal Contraception and Depression: Updated Evidence and Implications in Clinical Practice.

Hormonal contraceptives are used worldwide by more than 100 million women. Some studies have been published about the possible appearance of depressive symptoms when using hormonal contraceptives, but this link is still a matter of debate. The purpose of this review is to provide an update of the literature on this issue, and to investigate the possible explanations of this problem based on animal and human studies. The main pathway responsible for menstrual cycle-related mood changes is the γ-aminobutyric acid pathway, which is sensitive to changes in the levels of progesterone and of its metabolites, the neurosteroids. In particular, allopregnanolone is a potentiating neurosteroid with anxiolytic and anti-convulsant effects whose levels change during a normal menstrual cycle together with progesterone levels. Progestins have different effects on allopregnanolone, mainly owing to their diverse androgenicity. Moreover, they might affect brain structure and function, even though the meaning of these changes has yet to be clarified. It is important to define the groups of women in which negative mood disorders are more likely to occur. Adolescence is a critical period and this age-specific vulnerability is complex and likely bidirectional. Moreover, women with a history of mood affective disorders or premenstrual dysphoric syndrome are at a higher risk when taking contraceptives. In this review, we aim to provide clinicians with advice on how to approach these difficult situations.

Long-term treatment with α-lipoic acid and myo-inositol positively affects clinical and metabolic features of polycystic ovary syndrome.

The aim of this retrospective study was to evaluate the effects of a long-term treatment with α-lipoic acid (ALA) combined with myo-inositol (MI) on clinical and metabolic features of women with polycystic ovary syndrome (PCOS). Fifty-seven women with PCOS and a history of oligoamenorrhea were treated with MI and ALA (800 mg + 2000 mg per day). Forty-four of them had complete clinical charts and were considered eligible for the study. Information about cycle length and body mass index (BMI) was checked after 6, 12, and 24 months. After 12 months ovarian volume, total testosterone plasma levels and changes in hirsutism were also evaluated. The metabolic parameters were evaluated in 16 women after 6 and 18 months of the treatment. Cycle length was significantly reduced at 6 (p < .001), 12, and 24 months of treatment (p < .01). BMI showed a reduction only at 6 months (p < .05), thereafter returning similar to the basal values. No changes of testosterone and ovarian volume were observed. HOMA-IR and fasting insulin were unchanged, but the insulin response to a 3 h OGTT was improved after 6 (p < .01) and 18 months (p < .05) of treatment. No individual suffered from any adverse event. In conclusion, the combination of ALA and MI showed to be useful as long-term therapy in PCOS women, providing a normalization of the menstrual cycle and an amelioration of insulin levels with a high tolerability.

Treatment with d-chiro-inositol and alpha lipoic acid in the management of polycystic ovary syndrome.

To evaluate the effects of the combination of d-chiro inositol and alpha lipoic acid on menstrual cycles and insulin sensitivity in women with polycystic ovary syndrome (PCOS). Forty-one women with PCOS and 31 controls have been enrolled in the study. The menstrual cycle, BMI, homeostasis model assessment index (HOMA-I), and insulin secretion in response to an OGTT were evaluated before and after 6 months of treatment. During the observation period, the patients have been asked to not modify their diet and physical activity. The menstrual cycle length improved in 76.7% of the women. Ovulation was restored in 40%. During treatment, BMI significantly decreased (p<.002). The HOMA-I and insulin secretion were unchanged by treatment. However, when women were divided according to the presence of insulin resistance (IR; HOMA-I > 2.5), in those with IR the HOMA-I and the insulin secretion significantly decreased (p<.05 and p<.006). The association of d-chiro-inositol and alpha lipoic acid improves menstrual cycle length, restoring ovulation in the majority of women. Insulin sensitivity improved in women with IR only, confirming that in presence of IR the d-chiro-inositol has a role in restoring the insulin action overcoming the inactivity of epimerase in transforming myo-inositol to d-chiro inositol.

Observational prospective study on Lactobacillus plantarum P 17630 in the prevention of vaginal infections, during and after systemic antibiotic therapy or in women with recurrent vaginal or genitourinary infections.

We performed a prospective cohort parallel observational study on the use of Lactobacillus plantarum P 17630 in the prevention of vaginal infections. Eligible were women with a diagnosis of bacterial vaginosis (<15 days) and documented history of recurrent vaginal infections; and/or cystitis (<15 days); and/or treatment with antibiotics for bacterial respiratory tract infections during the week before the study entry. Study subjects were prescribed Lactobacillus plantarum P 17630 > 100.000.000 UFC one vaginal capsule per day for 6 days, then a capsule per week for 16 weeks. Eligible subjects were enrolled in two parallel cohorts: 85 women using (group A) and 39 not using (group B) Lactobacillus plantarum P 17630. The risk of recurrent infection within 4 months from the study entry, was higher among untreated women: multivariate OR 2.6 (95%CI 0.7-9.4). The modification of presence/intensity or symptoms was significant in both the study groups (p < .001). Impact statement What is already known on this subject? The Lactobacillus plantarum P 17630 has been shown to be active in the treatment of bacterial vaginosis and vaginal candidiasis. No data are available on its efficacy in the prevention of recurrent vaginal or urological infection or as a prevention strategy during systemic treatment with antibiotics. What do the results of this study add? This observational study suggests that Lactobacillus plantarum given for 4 months may lower the risk of recurrent infection in women with recurrent vaginal or genitourinary infection or after antibiotic systemic treatment for bacterial respiratory tract infection. The finding, however, is not statistically significant, possibly due to the lower than expected rate of infection observed in our population and consequently the limited power of the study. What are the implications of these findings for clinical practice and/or further research? New studies are needed in order to evaluate in different populations the role of Lactobacillus plantarum in lowering the risk of recurrent infection in a high-risk populations.

[Customization of hormonal contraception].

In the last few years new oral contraceptives have been marketed showing a better safety profile for women. They are the result of important changes made to the old compounds. As far as the estrogenic component, with the aim of decreasing side effects, the dose of ethinyl estradiol has been reduced and synthetic estrogens have been replaced by natural estradiol, further improving the safety profile. Also the progestin component in the last years has been changed in terms of dose, endocrine and metabolic characteristics. Levonorgestrel is an androgenic progestin, but now there is the possibility of choosing progestins without androgenic effect (gestodene and desogestrel) or progestins with antiandrogenic effect (cyproterone acetate, dienogest, drospirenone, chlormadinone acetate), very useful in patients with hyperandrogenism. Some of these progestins, like Drospirenone, represented the real held contributing, because of its antimineralcorticoid action, to reduce an important side effect like fluid retention; moreover there is the possibility to choose products with high progestogen effect on endometrium (dienogest, nomegestrole acetate), resulting very effective in women with abnormal uterine bleedings. Also the regimens of administration have been changed, by shortening or eliminating the tablet-free period; in this way the women may avoid premenstrual symptoms. The oral is not the only route of administration, but today there are alternative routes like transdermal, transvaginal, intrauterine and subcutaneous, reducing gastro-intestinal interferences and possible mistakes in pill intake.

Features of polycystic ovary syndrome (PCOS) in women with functional hypothalamic amenorrhea (FHA) may be reversible with recovery of menstrual function.

OBJECTIVE: Since features of polycystic ovary syndrome (PCOS) have been found to be prevalent in women with functional hypothalamic amenorrhea (FHA), we wished to determine what happens to these features after recovery of menstrual function in FHA Design: Prospective cohort study. Twenty-eight women with FHA and 30 age-matched ovulatory controls were studied. METHODS: Twenty-eight women with FHA and 30 age-matched ovulatory controls were studied. We measured serum estradiol, LH, FSH, testosterone, DHEAS, anti-Mullerian hormone (AMH), body mass index, and ovarian morphology on transvaginal ultrasound. RESULTS: At baseline, 12 of the 28 women (43%) had increased AMH (>4.7 ng/mL), and higher testosterone and larger ovaries compared to the other 16 women with normal AMH. One year after recovery of menstrual function, in the 12 women with increased AMH, serum AMH, testosterone and ovarian size decreased, while LH and estradiol increased. At one year, only one of the 12 women in the high AMH group developed clinical features of PCOS. CONCLUSIONS: In the majority of women with FHA who have PCOS-like features, these features may be due to the hypothalamic state and appear to be reversible. Few women may develop clinical PCOS after recovery.

Comparison of two insulin sensitizers, metformin and myo-inositol, in women with polycystic ovary syndrome (PCOS).

Insulin resistance (IR) plays a pivotal role in PCOS. Insulin-sensitizer agents such as metformin and inositols have been shown to improve the endocrine and metabolic aspects of PCOS. The purpose of this study is to compare their effects on the clinical and metabolic features of the women with PCOS. Fifty PCOS women with IR and/or hyperinsulinemia were randomized to treatment with metformin (1500 mg/day) or myo-inositol (4 g/day). IR was defined as HOMA-IR >2.5, while hyperinsulinemia was defined as a value of AUC for insulin after a glucose load over the cutoff of our laboratory obtained in normal women. The Matsusa Index has been calculated. The women have been evaluated for insulin secretion, BMI, menstrual cycle length, acne and hirsutism, at baseline and after 6 months of therapy. The results obtained in both groups were similar. The insulin sensitivity improved in both treatment groups. The BMI significantly decreased and the menstrual cycle was normalized in about 50% of the women. No significant changes in acne and hirsutism were observed. The two insulin-sensitizers, metformin and myo-inositol, show to be useful in PCOS women in lowering BMI and ameliorating insulin sensitivity, and improving menstrual cycle without significant differences between the two treatments.

Adolescents with Classical Polycystic Ovary Syndrome Have Alterations in the Surrogate Markers of Cardiovascular Disease but Not in the Endothelial Function. The Possible Benefits of Metformin.

STUDY OBJECTIVE: To study whether adolescents with the classical form of polycystic ovary syndrome (PCOS) have alterations in metabolic and vascular structure and function. The effect of metformin was evaluated. DESIGN: Controlled study. SETTING: University outpatient clinic. PARTICIPANTS: Eighteen nonobese adolescents with PCOS were enrolled. Seventeen healthy age-matched adolescents were recruited as control subjects. INTERVENTIONS: The metabolic profile and the endothelial structure and function were evaluated. MAIN OUTCOME MEASURES: Hormonal and lipid profile, blood pressure (BP) measurement, fasting glucose and insulin levels, C-reactive protein (CRP), homocysteine, tissue-type plasminogen activator, plasminogen activator inhibitor-1 (PAI-1), and plasmin-antiplasmin complexes (PAP) were measured. Flow mediated dilation (FMD), central pulse wave velocity (PWV), radial artery pulse wave, and common carotid intima-media thickness (IMT) were also assessed. Girls with PCOS were also studied 6 months after treatment with metformin (850 mg twice per day). RESULTS: Adolescents with PCOS were insulin resistant and/or hyperinsulinemic and they had higher BP values and levels of CRP and PAI-1 than the control subjects. The levels of tissue-type plasminogen activator and PAP were similar in both groups. FMD, PWV, and IMT were also similar. Metformin significantly (P < .05) reduced insulin, BP, CRP, and PAI-1 levels. The PAP levels significantly (P < .05) increased. Radial artery pulse wave was significantly reduced after metformin treatment. No modifications in FMD, PWV, and IMT were observed. CONCLUSION: Adolescents with classical PCOS have alterations in some surrogate markers of cardiovascular risk and they are ameliorated by metformin. No deterioration of vascular structure and function has been detected, probably because of the short duration of exposure to the disease.

Increased anti-Mullerian hormone levels and ovarian size in a subgroup of women with functional hypothalamic amenorrhea: further identification of the link between polycystic ovary syndrome and functional hypothalamic amenorrhea.

BACKGROUND: Functional hypothalamic amenorrhea is a disorder characterized by cessation of menstrual cycles in the absence of organic disease. In most patients, it occurs in adult life after a stressful event and may be related to a condition of mild chronic energy deprivation. The endocrine pattern is characterized by low estrogen levels with an absent response to a progestogen challenge test and low-normal gonadotropin levels. A few studies have shown that some of these women may have some features of polycystic ovary syndrome; these features include an increased androgen response to gonadotropins, increased anti-Mullerian hormone levels, and altered ovarian morphology or increased ovarian size. These findings suggest a link between these 2 completely different disorders: functional hypothalamic amenorrhea and polycystic ovary syndrome. The importance of the possible coexistence of these disorders in some women is important for follow-up of these women and in their treatment if they desire to become pregnant. OBJECTIVE: To determine whether a subgroup of well-characterized women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. STUDY DESIGN: Retrospective analysis of women with functional hypothalamic amenorrhea. Forty consecutive patients and 28 normal age-matched control patients were studied. Blood was obtained for serum anti-Mullerian hormone, androgens, and other hormone levels and all women had ovarian ultrasonographic measurements. RESULTS: In the entire group of women with functional hypothalamic amenorrhea, anti-Mullerian hormone and ovarian volume were greater than in control patients. In 13 patients (32.5%), anti-Mullerian hormone was elevated (>4.7 ng/mL, levels consistent with polycystic ovary syndrome) and in this group, ovarian volume was significantly greater than in the remaining patients with functional hypothalamic amenorrhea. Four of the 13 women with functional hypothalamic amenorrhea who had elevated anti-Mullerian hormone levels (10%), also had ovarian volume ≥10 cc (consistent with polycystic ovarian syndrome). In these patients all studied androgens were in the upper normal range or slightly elevated despite low-normal gonadotropins; mean total testosterone was significantly greater than in the other patients with increased anti-Mullerian hormone values with normal ovarian size (P<.05.) Six other women with functional hypothalamic amenorrhea who had increased anti-Mullerian hormone also had isolated elevations of some androgen levels, but mean testosterone and ovarian size were normal. CONCLUSIONS: As many as 10% of women with functional hypothalamic amenorrhea may have the coexistence of polycystic ovary syndrome. Because no signs or symptoms of this disorder were reported by these women before the appearance of the amenorrhea, it does not seem to be a coincidental relationship. The possibility that functional hypothalamic amenorrhea favors the appearance of polycystic ovary syndrome or more likely, that a mild (ovulatory) phenotype of polycystic ovary syndrome predisposes to the development of functional hypothalamic amenorrhea should be considered. Possible mechanisms are unclear and need to be investigated but may involve common vulnerabilities such as psychologic and mood disturbances.

AMH MEASUREMENT VERSUS OVARIAN ULTRASOUND IN THE DIAGNOSIS OF POLYCYSTIC OVARY SYNDROME IN DIFFERENT PHENOTYPES.

OBJECTIVE: This study was designed to assess the value of serum anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS) in various phenotypes and to assess ovarian ultrasound parameters. METHODS: We performed a retrospective matched controlled study of 113 females with various PCOS phenotypes and 47 matched controls. The diagnostic utility of AMH measurement and ovarian ultrasound were compared. Using receiver operating characteristic (ROC) curve analyses, the threshold for AMH (>4.7 ng/mL) and ultrasound parameters (follicle number per ovary [FNPO] >22 and ovarian volume [OV] >8 cc) were established. RESULTS: In the entire cohort, AMH had a low sensitivity of 79%; while FNPO and OV were 93% and 68%, respectively. Specificities ranged from 85 to 96%. In classic anovulatory PCOS, AMH exhibited a sensitivity of 91%, and for FNPO and OV the corresponding sensitivities were 92% and 72%. In the ovulatory phenotype, AMH sensitivity was only 50%, while FNPO and OV were 95% and 50%, respectively. In the nonhyperandrogenic phenotype, the sensitivity of AMH was 53% while those for FNPO and OV were 93% and 67%. CONCLUSION: AMH does not appear to be helpful for all subjects with PCOS but may be of some value in those who are anovulatory. However, FNPO was highly sensitive in all phenotypes, and was the single best criterion assessed for all subjects, suggesting the important role of ultrasound.

Unilateral adnexal agenesis and dermoid cyst: fertility implications.

We report the loss of potential fertility in a 23-year-old nulliparous woman who attended the outpatient gynaecological endocrinology clinic for amenorrhea and hot flushes started after a laparoscopic surgery for dermoid cyst. During surgery an unilateral ovarian and fallopian tube agenesis were found. The hormonal evaluation was performed. The results evidenced high plasma levels of LH and FSH. Their values were 56.6 and 121.3 mUI/ml, respectively. The concentrations of plasma E2 were < 20 pg/ml and of AMH were <0.08 ng/ml. Genetic analysis showed normal karyotype (46, XX). We think that if an embryological defect is suspected, an appropriate counselling about fertility preservation along with the assessment of hormonal levels before ovarian surgery should be recommended to all women in the reproductive age in order to offer future reproductive chances.

Insulin resistance and hyperandrogenism have no substantive association with birth weight in adolescents with polycystic ovary syndrome.

OBJECTIVE: To assess whether birth weight influences the metabolic and hormonal profile of adolescents with polycystic ovary syndrome (PCOS). DESIGN: Retrospective study. SETTING: University outpatient clinic. PATIENT(S): One hundred seventy consecutive adolescents 12 to 19 years of age with PCOS, 15 of whom were small for gestational age (SGA), and 75 healthy female aged-matched adolescents as controls. INTERVENTION(S): Physical evaluations, fasting blood samples for measuring endocrine and metabolic parameters, and an oral glucose tolerance test. MAIN OUTCOMES MEASURE(S): Physical, endocrine, and metabolic features. RESULT(S): The birth weights of adolescents with PCOS as well as those with hyperinsulinemic or insulin resistance were similar to those of the control group. The PCOS SGA adolescents had basal insulin (15.93 ± 7.16 µU/mL vs. 10.97 ± 5.79 µU/mL) and homeostasis model assessment of insulin resistance values (3.2 ± 1.54 vs. 2.19 ± 1.28) that were statistically significantly higher than in the control group. The mean levels of total testosterone in the SGA adolescents with PCOS were above the upper limit of the normal range (0.80 ng/mL). CONCLUSION(S): Low birth weight may influence the appearance of hyperandrogenism and insulin resistance in a portion of adolescents with PCOS, but only 9% of the adolescents with PCOS in this study were SGA. In the majority of adolescents with PCOS, hyperinsulinemia and hyperandrogenism are related to factors other than birth weight alone.

Effect of a new oral contraceptive with estradiol valerate/dienogest on carbohydrate metabolism.

BACKGROUND: Insulin resistance may be induced by both the estrogen and progestin component in hormonal contraception. When estrogen dose is reduced from 50 to 20 mcg, the extent of hyperinsulinemia decreases. Recently, the oral combination contraceptive (COC) containing estradiol valerate (E2V) in combination with dienogest (DNG) was developed in a new estrogen step-down, progesterone step-up dosing strategy (Qlaira, Bayer Healthcare Pharmaceuticals). This study was conducted to evaluate of the effect of a 3-month treatment with E2V/DNG on carbohydrate metabolism in women with polycystic ovarian syndrome (PCOS) and insulin resistance. STUDY DESIGN: Study consisted of subjects attending the gynecological clinic of Siena or Pisa, with PCOS and insulin resistance, and without contraindications for the use of COCs. PCOS females (n=20) aged 18 to 33 years were treated with a contraceptive formulation containing E2V/DNG for 3 months. Before treatment and during the third month of therapy, body mass index (BMI) measurement and an oral glucose tolerance test (OGTT) were performed. RESULTS: Median values of insulin after treatment were lower than median values before treatment. In particular, the median value of insulin at T0 was reduced by 54.6% (p<.001), and the mean difference between time 0 and 30 min was significantly reduced [42.96 (9.99) mU/mL vs 38.00 (15.10) mU/mL; p<.05]. Homeostasis model assessment of insulin resistance levels were significantly decreased following treatment. OGTT after treatment revealed median fasting glucose levels to be stable (p=.895) at T0. At T30, T60, T120 and T180 min, glucose median values were moderately reduced in comparison to median values before treatment. No significant difference was observed between median BMI values before [26 (4.8) kg/m(2)] and after treatment [26 (3.7) kg/m(2)]. CONCLUSIONS: Median insulin levels at T0 and the mean difference between time 0 and 30 of insulin following OGTT were significantly reduced than values before treatment with E2V/DNG for 3 months. Median BMI and glucose levels were not significantly modified. Natural estradiol and nonandrogenic progestogen in the Qlaira formulation could be recommended as an oral contraceptive in women with PCOS who are insulin resistant or who are overweight.