Sex-Specific Characteristics of the Microcirculation.

The requirements of metabolizing tissue are both continuous and variable; accordingly, the microvasculature serving that tissue must be similarly dynamic. Just as it is recognized that males and females of the same species have differing metabolic requirements, is it not likely that the microvasculature serving these tissues will differ by sex? This section focusing on the constituents of the microcirculation identifies what is known presently about the role sex plays in matching metabolic demand with microvascular function and areas requiring additional study. Many of the identified sex differences are subtle and easily ignored. In the aggregate, though, they can profoundly alter phenotype, especially under stressful conditions including pregnancy, exercise, and disease states ranging from diabetes to heart failure. Although the features presently identified to "have sex" range from differences in growth, morphology, protein expression, and intracellular signaling, males and females alike achieve homeostasis, likely by different means. Studies of microvascular sexual dimorphism are also identifying age as an independent but interacting factor requiring additional attention. Overall, attempting to ignore either sex and/or age is inappropriate and will prevent the design and implementation of appropriate interventions to present, ameliorate, or correct microvascular dysfunction.

Assessment of serum HE4 levels throughout the normal menstrual cycle.

BACKGROUND: Human epididymis protein 4 is a serum biomarker to aid in differentiating benign and malignant disease in women with a pelvic mass. Interpretation of human epididymis protein 4 results relies on robust normative data. OBJECTIVE: The purpose of this study was to evaluate whether human epididymis protein 4 levels are variable in women during the normal menstrual cycle. STUDY DESIGN: Healthy women, 18-45 years old, with regular menstrual cycles were recruited from community gynecologic practices in Rhode Island. Women consented to enroll and to participate by the donation of blood and urine samples at 5 specific times over the course of each cycle. Levels of reproductive hormones and human epididymis protein 4 were determined. Data were analyzed with the use of linear regression after log transformation. RESULTS: Among 74 enrolled cycles, 53 women had confirmed ovulation during the menstrual cycle and completed all 5 sample collections. Levels of estradiol, progesterone, and luteinizing hormone displayed the expected menstrual cycle patterns. Levels of human epididymis protein 4 in serum were relatively stable across the menstrual cycle, except for a small ovulatory (median, 37.0 pM) increase. Levels of human epididymis protein 4 in urine, after correction for creatinine, displayed the same pattern of secretion observed in serum. CONCLUSION: Serum human epididymis protein 4 levels are relatively stable across the menstrual cycle of reproductive-aged women and can be determined on any day to evaluate risk of ovarian malignancy. A slight increase is expected at ovulation; but even with this higher human epididymis protein 4 level, results are well within the healthy reference range for women (<120 pM). Levels of human epididymis protein 4 in urine warrant further investigation for use in clinical practice as a simple and convenient sample.

Assessment of bronchial responsiveness on exposure to isometric exercise during different phases of menstrual cycle: a pilot study.

OBJECTIVES: The present study was planned to assess the effects of gonadal steroids (estrogen and progesterone) on bronchial responsiveness, before and after handgrip exercise, during different phases of menstrual cycle. MATERIALS AND METHODS: In this study, 30 healthy (25-40 years), non-athletic, adult female volunteers were studied. The various pulmonary function parameters (FVC, FEV1, PEFR, FEF 25-75%) were recorded with a spirometer under resting conditions and then within five minutes of cessation of isometric exercise. Recordings were taken during the Menstrual phase (MP), Proliferative phase (PP), and Luteal phase (LP) of menstrual cycle and were confirmed by plasma levels of estrogen and progesterone. The oral temperature was recorded during each phase of the menstrual cycle. RESULTS: Under resting conditions, the above-mentioned parameters did not reveal significant differences during the three phases. A significant fall was observed only in the Peak Expiratory Flow Rate (PEFR) during all the phases after handgrip, but there was a non-significant decline in the other parameters. CONCLUSION: By this study we conclude that the physiological changes in hormone levels during the menstrual cycle are not in themselves associated with changes in airway responsiveness before and after the handgrip test. The general fall seen in the pulmonary parameters could be due to fatigue or psychic factors.

Characteristics of menstrual cycle in shift workers.

BACKGROUND: In this study, the characteristics of menstrual cycle in shift workers employed in the pharmaceutical industry are investigated. METHOD: This study was conducted in a pharmaceutical industrial complex in Tehran in 2012. 406 female workers in packaging units were studied on the menstrual cycle characteristics. The studied workers were divided into two groups of shift workers and non-shift workers and were compared in terms of the frequency of menstrual disorder (short-term cycle, long-term cycle, irregular cycle and bleeding during menstrual cycle) as well as hormonal values (FSH, LH, TSH, and Prolactin). RESULTS: The odds ratio (OR) for menstrual disorder in the shift workers was 5.54 (95% CI=2.78-11.02) compared to the non-shift workers. The mean difference of hormonal values (except prolactin) between shift workers and non-shift workers was not significant (P>0.05). CONCLUSION: This study suggests that shift work may disrupt the menstrual cycle.

[Assessment of the results of determination of the blood level of dehydroepiandrosterone sulfate by using various commercial reagents].

The results of determination of the blood levels of dehydroepiandrosterone (DHEA) sulfate (DHEA-S) were comparatively assessed, by using the test systems "Steroid-IEA-DHEA-sulfate" (ZAO "Alkor Bio" (Saint Petersburg, Russia)) and "DHEA-S ELISA ("DRG Instruments GmbH (Germany)). The studies were conducted in apparently healthy 19-59-year-old women living in the middle belt of Western Siberia. They revealed the high sensitivity of the study test systems to age-related changes in the blood concentration of DHEA-S. The normal blood DHEA-S concentrations levels given in the instruction to the "DHEA-S ELISA" test systems were found to be decreased in they are used to measure the content of the above analyzed parameter in women aged 19-39 years.

Pituitary-ovarian axis during lactational amenorrhoea. II. Longitudinal assessment of serum FSH polymorphism before and after recovery of menstrual cycles.

BACKGROUND: The association of normal serum levels of immunoassayable gonadotrophins with anovulation during lactational amenorrhoea (LA) has not been fully explained. METHODS: Serum FSH polymorphism was analysed in 10 women during LA between days 60 and 70 post-partum and again, in the mid-follicular phase (MFP), after resuming menstrual cyclicity. FSH microheterogeneity was characterized according to charge, using preparative isoelectric focusing, and according to the inner structure of carbohydrate chains, using lectin chromatography. RESULTS: A significantly higher proportion of FSH charge isoforms isolated below pH 4.10 and a lower proportion of FSH isoforms bearing highly branched oligosaccharides were observed during LA when compared to MFP. Further analysis with higher resolution showed that FSH charge isoforms, isolated in the lower pH range in LA, corresponded to FSH molecules bearing highly branched and biantennary oligosaccharides. FSH isoforms bearing hybrid-type oligosaccharides were only present during LA. The circulating FSH isoform mix was significantly less bioactive in LA than in MFP. LA is characterized by a more acidic mix of FSH isoforms, containing hormone bearing less processed oligosaccharides, with decreased biopotency in comparison with the follicular phase. CONCLUSIONS: This FSH microheterogeneity may be one of the critical factors contributing to incomplete follicular development and anovulation during LA.

Pituitary-ovarian axis during lactational amenorrhoea. I. Longitudinal assessment of follicular growth, gonadotrophins, sex steroids and inhibin levels before and after recovery of menstrual cyclicity.

BACKGROUND: Comparisons of follicular development and hormonal profile in the same women during and after lactational amenorrhoea (LA) are scarce. We report follicular growth, pituitary and ovarian hormone serum levels in the same women during LA and in follicular phases after resumption of menstrual cyclicity. METHODS: Serum samples were obtained from 10 women during LA between days 60 and 89 post-partum and between days 1 and 4 (early follicular phase; EFP) and 7 and 10 (mid-follicular phase; MFP) of the second and third cycles after LA. RESULTS: The number of follicles >3 mm and diameter of the largest follicle were significantly higher during LA when compared to EFP and MFP. Serum levels of inhibin B were similar in LA and EFP and increased significantly in MFP. Pro-alphaC was significantly higher in EFP than in LA and MFP. Estradiol was similar during all stages. In comparison with EFP and MFP, LA is associated with higher prolactin levels, normal or slightly elevated gonadotrophins and increased number and size of follicles without a parallel increase in estradiol, inhibin B and Pro-alphaC. CONCLUSIONS: During LA, there is a profound dissociation between follicular growth and follicular endocrine activity, which suggests an alteration in the stimulus-response relationship at the follicular level.

Hormonal assessment of women submitted to tubal ligation.

Sixteen fertile women aged 30-35 years with regular menstruations were studied before and 6 months after tubal ligation (TL). The diagnosis of ovulation was based on clinical ultrasonographic and hormonal parameters [follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2 and P4]. The menstrual pattern did not vary before and after surgery. Follicular or luteal phase FSH and E2 levels did not differ between the pre- and post-TL period. Luteinizing hormone levels on days -2 and 0 of the follicular phase were significantly higher during the post-TL period, while no difference was observed for the luteal phase. P4 levels during the follicular phase did not differ between the two periods, except for day -4, while they were lower during the post-TL luteal phase. The results of the study suggest that in the present patient group, no modifications in the menstrual pattern could be observed 6 months after TL, and TL appears not to interfere with ovulation. Luteinizing hormone levels showed an increase during the ovulatory period after TL, and progesterone secretion decreased during the post-TL luteal phase.

Fine tuning cycle day 3 hormonal assessment of ovarian reserve improves in vitro fertilization outcome in gonadotropin-releasing hormone antagonist cycles.

OBJECTIVE: To identify the cut-off values of the baseline (cycle day 3) levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E(2)) for improving the outcome prediction of GnRH antagonist in vitro fertilization (IVF) cycles and to determine whether the predictive accuracy of these values is affected by the patient's clinical prognosis. DESIGN: Retrospective analysis. SETTING: An IVF clinic in a tertiary medical center. Women undergoing 230 consecutive IVF cycles using a GnRH antagonist protocol. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Outcome of IVF, measured by ovarian response and pregnancy rates. RESULT(S): Lower baseline levels of FSH and E(2), but not LH, correlated with improved ovarian response and pregnancy rates in IVF cycles using a GnRH antagonist. Compared with our currently used criteria, the cut-off values of FSH <10 IU/L and E(2) <56 pg/mL would have significantly improved the IVF outcome in a population of patients with normal prognosis. However, a stricter baseline FSH cut-off value of 8 IU/L would have been required to improve the IVF outcome in a population of patients with a poor prognosis. CONCLUSION(S): The outcome of IVF may be improved by modifying the hormonal starting criteria to take into account individual patient characteristics such as clinical prognosis.

The optimal timing of blood collection during the menstrual cycle for the assessment of endogenous sex hormones: can interindividual differences in levels over the whole cycle be assessed on a single day?

The objective of this study was to identify the optimal timing of sampling during the menstrual cycle for assessment of interindividual variation in exposure to endogenous sex hormones, including estradiol, progesterone, and the free androgen index. Twenty-four healthy premenopausal women with regular periods were recruited, and alternate day venous blood samples were taken in the morning throughout one menstrual cycle. Spearman rank correlation coefficients were calculated for the estimates of average hormone levels (based on area under the curve) over one menstrual cycle against values on single days within that cycle. Days within the menstrual cycle were identified that provided the best assessment of interindividual differences. The most consistent correlation for estradiol was seen between days 9 and 11 (e.g., r = 0.53 and P = 0.01, day 10), the most consistent correlation for progesterone was seen between days 17 and 21 (e.g., r = 0.80 and P < 0.001, day 20), and the most consistent correlation for free androgen index was seen between days 12 and 15 (e.g., r = 0.90 and P < 0.001, day 15). Post hoc analysis of estradiol and progesterone levels on days counted back from the start of the next menstrual cycle identified marginally stronger associations. On repeat hormone measurements (not done for progesterone) on days 10 and 15, two to five menstrual cycles later, correlation coefficients with the original hormone levels remained reasonable (> or =0.55) for most. In conclusion, a reasonable characterization of interindividual differences in premenopausal estradiol, androgen, and progesterone levels may be achieved with single blood samples taken on specific days. This provides a useful approach for future epidemiological studies.

Glucose metabolism during the menstrual cycle. Assessment with the euglycemic, hyperinsulinemic clamp.

To assess tissue sensitivity to insulin during the follicular and luteal phases of the menstrual cycle, two-step euglycemic, hyperinsulinemic clamp studies in combination with tritiated glucose infusion and indirect calorimetry were performed in regularly menstruating women in randomized order. There was no difference in the basal follicular and luteal phase levels of glucose, insulin or glucose turnover. A low-dose (0.25 mU/kg/min) insulin infusion suppressed endogenous hepatic glucose production. There was no difference in tissue insulin sensitivity during a high-dose insulin infusion (1.0 mU/kg/min). Nonoxidative glucose disposal also was similar in the basal and insulin infusion periods. Under euglycemic, hyperinsulinemic conditions, there is no difference in tissue sensitivity to insulin, and intracellular pathways of glucose disposal are not altered by the stage of the menstrual cycle.

A biochemical test for the direct assessment of endometrial function: measurement of the major secretory endometrial protein PP14 in serum during menstruation in relation to ovulation and luteal function.

Circulating PP14 was measured by radioimmunoassay in ovulating (n = 12) and anovulatory (n = 3) women throughout the menstrual cycle, the highest levels of serum PP14 being seen during menstruation and in the late luteal phase in ovulating women. Mean serum PP14 levels on days 1-7 and 24-28 of the menstrual cycle were significantly higher than those observed from days 8 to 23 (P less than 0.0005 and P = 0.005 respectively). There was no difference in mean PP14 levels observed in the menstrual and luteal phase. By contrast, serum PP14 was rarely detected in anovulatory cycles. During the luteal phase, mean serum PP14 levels were apparently not related to serum progesterone levels. However, mean PP14 levels during the menstrual phase were significantly higher in the group of women with the highest progesterone production (Pmax greater than 39 nmol/l) (P less than 0.002) in comparison with levels seen in ovulating women with lower progesterone production (Pmax less than 32 nmol/l). These findings suggest that the synthesis and secretion of PP14 is influenced by ovulation and luteal function. Serum PP14 measurements may provide useful information about the endometrium in relation to fertility, and that these measurements during the menstrual cycle may distinguish between ovulatory and anovulatory cycles.

Cyclic changes of the functional ovarian compartments: echographic assessment.

Using bidimensional echography, 25 normal ovulatory cycles were evaluated. The following parameters were assessed: 1) ovarian volume, 2) volume of the dominant follicle, 3) corpus luteum volume, 4) residual follicular volume, and 5) stromal volume. Ovarian volume and dominant follicle volumes reached their maximum on day -1: 11.68 +/- 2.87 ml and 3.60 +/- 1.20 ml respectively. The maximum stromal volume was seen during the follicular phase: 7.98 +/- 2.29 ml. In the dominant ovary the maximum corpus luteum volume was observed on day +1 and the maximum stromal volume on day +7 (8.64 +/- 2.53 ml). In the contralateral ovary, the stromal volume did not show significant changes. The residual follicular volume in both ovaries diminished gradually from the early follicular phase except for a slight postovulatory rise. In this study, normal values during the ovulatory cycle were obtained as indicated above. The use of bidimensional echography in the diagnosis of functional disorders of the ovary is stressed.