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Purpose Controlled ovarian stimulation significantly amplifies the number of maturing and ovulated follicles as well as ovarian steroid production. The ovarian hyperstimulation syndrome (OHSS) increases capillary permeability and fluid extravasation. Vascular integrity intensely is regulated by an endothelial glycocalyx (EGX) and we have shown that ovulatory cycles are associated with shedding of EGX components. This study investigates if controlled ovarian stimulation impacts on the integrity of the endothelial glycocalyx as this might explain key pathomechanisms of the OHSS. Methods Serum levels of endothelial glycocalyx components of infertility patients (n=18) undergoing controlled ovarian stimulation were compared to a control group of healthy women with regular ovulatory cycles (n=17). Results Patients during luteal phases of controlled ovarian stimulation cycles as compared to normal ovulatory cycles showed significantly increased Syndecan-1 serum concentrations (12.6 ng/ml 6.1125th–19.1375th to 13.9 ng/ml 9.625th–28.975th; p=0.026), indicating shedding and degradation of the EGX. Conclusion A shedding of EGX components during ovarian stimulation has not yet been described. Our study suggests that ovarian stimulation may affect the integrity of the endothelial surface layer and increasing vascular permeability. This could explain key features of the OHSS and provide new ways of prevention of this serious condition of assisted reproduction.

Steroid cell tumors not otherwise specified are one of the rare virilizing ovarian tumors. Most of the tumors are benign. This case report illustrates the challenge in managing steroid cell tumor not otherwise specified, which starts from determining its malignant potential, surveillance, and adjuvant treatment option.

This paper is dedicated to the memory of the first professor of Behavioral Endocrinology in the Faculty of Psychology at the University of Granada, Prof. Filomena Molina. We are grateful to Daniel Robert Caldera Jr. for his assistance with the English. This study was supported by the Spanish Ministry of Economy, Industry and Competitiveness (National I + D Plan: PSI2017-89324-C2-1-P and PSI2017-89324C2-2-P). Funding for open access charge: Universidad de Granada/CBUA., Estradiol is an ovarian steroid hormone that peaks shortly before ovulation and significantly affects various brain regions and neurotransmitter systems, with similar and differential effects with progesterone, another ovarian hormone. Studies investigating the neurocognitive processes during the menstrual cycle have focused on the early follicular phase (EFP) characterized by low estradiol and progesterone levels and the mid-luteal phase (MLP) with high estradiol and progesterone levels. However, most studies have failed to include the ovulatory phase, characterized by high estradiol and low progesterone levels. Given the various hormonal changes in the menstrual cycle, we revisited studies suggesting that the menstrual cycle did not affect verbal and spatial abilities and observed that many contain mixed results. Comparing these studies makes it possible to identify relevant modulating factors, such as sample size, participant age, accurate selection of days for testing, asymmetrical practice effects, genetic polymorphisms, and task difficulty. More robust findings are related to improved mental rotation capacity during EFP with challenging tasks and differences in brain activation among menstrual cycle phases during the execution of spatial and verbal tasks. During MLP, less robust findings were observed, possibly modulated by the complex effects of the two hormones on the brain. In conclusion, we propose that it is crucial to include all three menstrual cycle phases and consider these modulating factors to avoid confounding findings., Spanish Ministry of Economy, Industry and Competitiveness PSI2017-89324-C2-1-P PSI2017-89324C2-2-P, Universidad de Granada/CBUA

STUDY QUESTION Is psychosocial stress associated with ovarian function in reproductive-aged survivors of cancer diagnosed as adolescents and young adults (AYA survivors)? SUMMARY ANSWER We observed no association between self-reported and biomarkers of psychosocial stress and ovarian function in AYA survivors. WHAT IS KNOWN ALREADY Psychosocial stress suppresses hypothalamic-pituitary-ovarian axis, resulting in ovulatory dysfunction, decreased sex steroidogenesis and lower fertility in reproductive-aged women. Many cancer survivors experience high psychosocial stress and hypothalamic-pituitary-adrenal axis dysregulation. The menstrual pattern disturbances and infertility they experience have been attributed to ovarian follicle destruction, but the contribution of psychosocial stress to these phenotypes is unknown. STUDY DESIGN, SIZE, DURATION A cross-sectional study was conducted estimating the association between perceived stress, measured by self-report and saliva cortisol, and ovarian function, measured by bleeding pattern, dried blood spot (DBS) FSH and LH, and saliva estradiol. We included 377 AYA survivor participants. PARTICIPANTS/MATERIALS, SETTING, METHODS AYA survivor participants were ages 15–35 at cancer diagnosis and ages 18–40 at study enrollment, had completed primary cancer treatment, had a uterus and at least one ovary, did not have uncontrolled endocrinopathy and were not on hormone therapy. Recruited from cancer registries, physician referrals and cancer advocacy groups, participants provided self-reported information on psychosocial stress (Perceived Stress Scale-10 (PSS-10)) and on cancer and reproductive (fertility, contraception, menstrual pattern) characteristics. DBS samples were collected timed to the early follicular phase (cycle Days 3–7) for menstruating individuals and on a random day for amenorrheic individuals; saliva samples were collected three time points within 1 day. FSH and LH were measured by DBS ELISAs, cortisol was measured by ELISA and estradiol was measured by liquid chromatography tandem mass spectrometry. MAIN RESULTS AND THE ROLE OF CHANCE The median age of participants was 34.0 years (range 19–41) at a median of 6.0 years since cancer diagnosis. The most common cancer was breast (32.1%). Median PSS-10 score was 15 (range 0–36), with 5.3% scoring ≥26, the cut point suggestive of severe stress. Cortisol levels followed a diurnal pattern and cortisol AUC was negatively correlated with PSS-10 scores (P = 0.03). Neither PSS-10 scores nor cortisol AUC were associated with FSH, LH, estradiol levels or menstrual pattern. Waking and evening cortisol and the cortisol awakening response also were not related to ovarian function measures. LIMITATIONS, REASONS FOR CAUTION Our analysis is limited by its cross-sectional nature, heterogeneity of cancer diagnosis and treatments and low prevalence of severe stress. WIDER IMPLICATIONS OF THE FINDINGS The lack of association between psychosocial stress and a variety of ovarian function measures in female AYA cancer survivors suggests that psychosocial stress does not have a significant impact on the reproductive axis of AYA survivors. This finding is important in counseling this population on their menstrual pattern and family building plans. STUDY FUNDING/COMPETING INTEREST(S) NIH HD080952, South Korea Health Industry Development Institute HI18C1837 (JK). Dr A.D. works for Bluebird Bio, Inc., Dr D.Z. works for ZRT Labs and Dr P.M.S. works for Ansh Labs, which did not sponsor, support or have oversight of this research. Other authors report no competing interests. TRIAL REGISTRATION NUMBER N/A

The role of reproductive steroids in the pathophysiology or treatment of traditional affective disorders remains unestablished. However, there is strong evidence documenting roles of ovarian steroids in reproductive endocrine-related mood disorders including Premenstrual Dysphoric Disorder (PMDD). Studies in PMDD have consistently demonstrated the absence of a deficiency or excess of circulating ovarian steroid hormones. Thus, if ovarian steroids play a role in PMDD, the pathophysiologic paradigm is that normal levels of ovarian steroids induce an abnormal behavioral state in those women with PMDD but not those without PMDD. Recent studies have demonstrated that it is the change in ovarian steroid levels rather than stable levels that trigger the altered affective state in PMDD. Neuroimaging studies have identified potential neural targets of ovarian steroids in women with PMDD within several large-scale brain networks, including the prefrontal cortex and regions involved in affect regulation. Finally, preliminary findings suggest that an intrinsic cellular difference confers a differential response to ovarian steroids in women with PMDD compared with those who do not experience this condition.

Ovarian steroid cell tumours are an uncommon cause of virilisation. They may originate from the stroma or sex cords; sometimes the tumour lineage is unknown, in which case the tumour is described as “not otherwise specified”. We report the case of a patient with signs of rapidly progressive virilisation, suggestive of ovarian origin. Imaging tests were negative. After surgical intervention, the presence of microscopic tumour markers positive for steroid cells was observed.

This study aimed to document the seasonal cycle of steroid levels in the plasma and ovary, including testosterone (T), estradiol-17&beta, (E2) and 17&alpha, 20&beta, dihydroxy-4-pregnen-3-one (DHP) in relation to ovarian development in wild populations of female blue tang fish. The gonadosomatic index (GSI%) maintained high values from April to July and increased from the II to IV ovarian stages and dropped in the V stage. Levels of plasma, ovary T and E2 and DHP were high from March to July. Plasma T and E2 levels were low in the II stage when most oocytes were previtellogenic, reaching a peak during spawning, and decreased in the V stages when fish were going to late spawning and termination. DHP was detected in all stages of the ovary with a higher level in spawning fish but decreased after spawning. These results revealed that T, E2 and DHP could be involved in ovarian development and DHP may play a significant role as a maturational inducing hormone in blue tang fish.

The human endometrium is the main target organ for the ovarian steroidal hormones. The pivotal role of sex hormones in the development, growth and maintenance of the normal physiological endometrium is well established. Aberrations in the endometrial hormonal milieu due to endogenous or exogenous factors influence endometrial carcinogenesis and cancer progression. Emerging evidence suggests that other non-steroid hormones are involved in endometrial carcinogenesis via altering the tumour microenvironment and facilitating tumour progression. Understanding the intricate relationship between these hormones in endometrial carcinogenesis could improve the current therapeutic options and lead to the designing of new strategies for the prevention and treatment of endometrial cancer in the era of evolving hormone therapy. This chapter focuses on the influences of both ovarian steroid hormones and the other non-steroidal hormones in endometrial cancer.

Migraine is three times more prevalent in women than in men. The mechanisms behind the sex disparity in migraine are not completely understood, but it is thought to be mediated through changes in ovarian steroid hormones. Migraine pathophysiology is considered to involve an activation of the trigeminovascular system and the subsequent release of calcitonin gene-related peptide (CGRP); therefore, an interaction between ovarian steroid hormones, the trigeminovascular system, and CGRP has been suggested. Although studies are scarce, it has been shown that indeed there is a cross talk and that further studies could lead to the development of sex-specific treatments.

Oviductal motility is required for transport of oocyte and embryo resulting in successful fertilization and implantation in mammals. The oviduct consists of epithelial, stromal and smooth muscle layers. Oviductal motility is systemically and locally regulated by various factors including prostaglandin F2 alpha (PGF) and endothelins (EDNs), and relaxing factors including prostaglandin E2 (PGE2) and nitric oxide (NO). The objective of our research is to clarify the regulatory system of oviductal motility including the production mechanisms of these factors in cattle. First, the expressions of regulating factors of oviductal motility were examined throughout the estrous cycle in the bovine oviduct. Some of them showed cyclical changes, which suggested that they were controlled by some other factors. Second, the effects of ovarian steroids or oviductal local factors on the expressions of PGs, EDNs and NO synthases were investigated using cell culture method. Several factors such as estradiol‒17beta, progesterone and lysophosphatidic acid affected the expressions of regulating factors of smooth muscle motility. In addition, we found that these actions differed between the ampulla and isthmus in same types of cultured cell. Our studies suggest that regulatory factors of oviductal motility are produced during the optimal period and at proper location to transport the oocyte and early embryo in the bovine oviduct. Although the precise control of oviductal motility is essential for successful pregnancy, methods for diagnosing and treating of its functional abnormality have not been established yet not only in cows but also in other animals including human. Our studies should contribute to improving the fertility rates in mammals.

The aim of our study was to understand whether ovarian steroid hormones, and their response to the metabolic hormones leptin and IGF-I leptin, could be involved in the control of mink reproductive aging via changes in basal release of ovarian progesterone and estradiol. For this purpose, we compared the release of progesterone and estradiol by ovarian fragments isolated from young (yearlings) and old (3-5 years of age) minks cultured with and without leptin and IGF-I (0, 1, 10 or 100 ng/ml). We observed that isolated ovaries of older animals produced less progesterone but not less estradiol than the ovaries of young animals. Leptin addition stimulated estradiol release by the ovarian tissue of young animals but inhibited it in older females. Leptin did not influence progesterone output by the ovaries of either young or older animals. IGF-I inhibited estradiol output in young but not old animals, whereas progesterone release was inhibited by IGF-I irrespective of the animal age. Our observations demonstrate the involvement of both leptin and IGF-I in the control of mink ovarian steroid hormones release. Furthermore, our findings suggest that reproductive aging in minks can be due to (a) reduction in basal progesterone release and (b) alterations in the response of estradiol but not of progesterone to leptin and IGF-I., Summary: Both leptin and IGF-I are involved in the control of mink ovarian steroid hormone release. Reproductive aging can be due to (a) reduction in basal progesterone release and (b) alterations in the response of estradiol but not of progesterone to leptin and IGF-I.

The Fallopian tubes are parts of the female reproductive tract responsible for the gamete transport and are the site for fertilization and preimplantation embryo development. This article discusses the morphology, physiology, and cell biology of each segment in the Fallopian tubes. The responsiveness of the Fallopian tubes to ovarian steroid hormones (estrogen and progesterone) and health conditions related to defective Fallopian tubes are also discussed.

Embryo implantation involves the implantation-competent blastocyst and the uterus at the receptive state. As to the uterus, it must enter into the receptive state to accept the embryo. Uterine receptivity is defined as a limited period when the uterine environment is conducive to blastocyst acceptance and implantation. This article reviews the concept of uterine receptivity, the contributions of the uterus and blastocyst to the preparation of uterine receptivity, how the uterine receptivity is controlled by ovarian steroid hormones, and the ways to prolong the duration of uterine receptivity.

This study aimed at examining the secretion activity of steroid hormones progesterone and 17β-estradiol by porcine ovarian granulosa cells after addition of green tea extract. Granulosa cells were incubated with green tea extract (at doses of 0.01, 0.1, 1, 10 and 100 μg.ml-1). Another set of cells were incubated with green tea extract at the above doses along with additional supplementation of follicle stimulating hormone (FSH) at 10 μg.ml-1. Release of hormones by granulosa cells was assessed by EIA after 24 h exposure. Secretion of steroid hormones was not affected either by green tea extract alone or after FSH supplementation with green tea extract. Results indicate that ovarian steroidogenesis is not affected by green tea under conditions used in the experiment.

Ovarian steroid cell tumors are very rare but potentially life-threatening neoplasms. They represent less than 0.1% of all ovarian tumors, typically present in premenopausal women and frequently manifest with virilization. Signs of hyperandrogenism may appear in postmenopausal women due to tumorοus and non-tumorοus adrenal and ovarian causes as well due to the normal aging process. In any case, steroid cell tumor should be suspected in postmenopausal women who present with rapid progressive androgen excess symptoms. This report describes a case of a 67-year-old postmenopausal woman with signs of hyperandrogenism, where an ovarian steroid cell tumor was diagnosed and treated by laparoscopic bilateral salpingo-oophorectomy and synchronous hysterectomy.

Premenstrual dysphoric disorder (PMDD) symptoms are eliminated by ovarian suppression and stimulated by administration of ovarian steroids, yet they appear with ovarian steroid levels indistinguishable from those in women without PMDD. Thus, symptoms could be precipitated either by an acute change in ovarian steroid levels or by stable levels above a critical threshold playing a permissive role in expression of an underlying infradian affective "pacemaker." The authors attempted to determine which condition triggers PMDD symptoms.The study included 22 women with PMDD, ages 30 to 50 years. Twelve women who experienced symptom remission after 2-3 months of GnRH agonist-induced ovarian suppression (leuprolide) then received 1 month of single-blind (participant only) placebo and then 3 months of continuous combined estradiol/progesterone. Primary outcome measures were the Rating for Premenstrual Tension observer and self-ratings completed every 2 weeks during clinic visits. Multivariate repeated-measure ANOVA for mixed models was employed.Both self- and observer-rated scores on the Rating for Premenstrual Tension were significantly increased (more symptomatic) during the first month of combined estradiol/progesterone compared with the last month of leuprolide alone, the placebo month, and the second and third months of estradiol/progesterone. There were no significant differences in symptom severity between the last month of leuprolide alone, placebo month, or second and third months of estradiol/progesterone. Finally, the Rating for Premenstrual Tension scores in the second and third estradiol/progesterone months did not significantly differ.The findings demonstrate that the change in estradiol/progesterone levels from low to high, and not the steady-state level, was associated with onset of PMDD symptoms. Therapeutic efforts to modulate the change in steroid levels proximate to ovulation merit further study.

The purpose of this study was to investigate whether fertile or non-fertile inseminations (AI) in synchronized ewes are correlated with the electrical resistance of cervical mucus (ERCM) and the ovarian steroid concentration. AIs were performed either at fixed-time (group A) or after estrus detection (group B). Retrospective analysis revealed that at AI, pregnant ewes had lower ERCM values and progesterone concentrations than non-pregnant ones (p < 0.05). It appears that ERCM may be used as an additional index for fertility enhancement of inseminated ewes.

Background: Ovarian steroid cell tumors (SCTs) are rare and usually benign, although 25-43% are reportedly malignant. The cytologic findings of these rare ovarian tumors have almost never been reported. Case: We report a rare case of a malignant ovarian SCT with peritoneal dissemination and malignant ascites in a 40-year-old woman. Her tumor was classified as stage IIB (pT2bNoM0) according to the FIGO (International Federation of Gynecology and Obstetrics) classification system, and she was treated with adjuvant chemotherapy following staging laparotomy. Cytology of the ascitic fluid revealed large, polygonal-to-round cells and multinucleated cells with atypia, appearing in clusters with slight overlapping or as isolated tumor cells. Numerous tumor cells had small central round or eccentric nuclei with conspicuous nucleoli, and a moderate-to-abundant amount of cytoplasm, varying from granular and eosinophilic to pale and multivacuolated (foamy), with cannibalism formations. The nuclear chromatin was fine and granular, with irregular distribution and nuclear-membrane thickening. Conclusion: These may be the first reported cytology results for ascites with a malignant SCT. Our patient's cytological ascitic findings, rather than the histopathologic features of the original and disseminated tumors, represent the malignant features of the tumor.