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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.

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.

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

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.

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.

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.

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.

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.

Hereditary leiomyomatosis and renal cell carcinoma syndrome (HLRCC) is a rare autosomal dominant syndrome associated with heterozygous germline mutations of the fumarate hydratase ( FH ) gene on chromosome 1q42.3-43. Common clinical manifestations include cutaneous and uterine leiomyomas (LMs) and renal cancer. While rare/solitary cases of uterine leiomyosarcomas, bilateral macronodular adrenocortical disease (BMAD), Leydig cell tumors of testis, and ovarian cystadenomas have …

The concept that adrenal androgen production gradually declines with age has changed following the analysis of the longitudinal data collected in the Study of Women’s Health Across the Nation (SWAN). It is now recognized that four adrenal androgens (3-beta hydroxy-5-androsten-17-one or dehydroepiandrosterone--DHEA, its sulfate, dehydroepiandrosterone sulfate--DHEAS; androst-4-ene, 3,17-dione or androstenedione; and androst-5-ene-3-beta, 17-beta diol, also known as androstenediol or Adiol) rise during the menopausal transition in most women. Ethnic and individual differences in sex steroids are more apparent in circulating adrenal steroids than in either estradiol or cyclic ovarian steroid hormone profiles, particularly during the early and late perimenopause. Thus, adrenal steroid production may play a larger role in the occurrence of symptoms and the potential for healthier aging than previously recognized.

Objectives—Magnetic resonance imaging (MRI) studies report hippocampal (HC) volume reductions in depression. Despite observations in the HC of functional heterogeneity and ovarian steroid influence, few studies report regional volume alterations or control for menstrual cycle phase. Using in vitro methods, we recently observed reduced anterior HC volume in antidepressant-naive, ovarian-intact, behaviorally depressed adult female monkeys. The purpose of this study was to confirm these findings in vivo and examine whether lack of ovarian steroids affects the relationship between depression and HC volume. Methods—MRI was used to measure whole, anterior, and posterior HC volumes in a matched sample of antidepressant-naive, surgically-postmenopausal, adult female cynomolgus macaques characterized for behavioral depression (n=6 depressed, 6 nondepressed). High resolution structural MRIs were acquired, and HC regions of interest were manually segmented. HC volumes were normalized to whole brain volumes prior to analysis. Results—Similar to the previous in vitro study, HC volume measured in vivo was associated with depression. In contrast to the previous study of ovarian-intact females, whole, anterior and posterior volumes of both left and right HC were significantly smaller in depressed compared to nondepressed surgically postmenopausal females. Conclusions—These findings confirm and extend previous observations of smaller HC volumes in behaviorally depressed female monkeys, and suggest a possible role for ovarian steroids in HC protection in depression. Further studies of the potential modulating effects of ovarian function on the relationship between depression and HC volume are warranted.

Ovarian steroid cell tumours (not otherwise specified) are rare neoplasms of the ovary and are classified under lipid cell tumours. Their diagnosis can be considered as one of exclusion. Histopathologically, the tumour should carefully be evaluated for microscopic features of malignancy, but it is essential for the clinician and the pathologist to remember that in these tumours, pathologically benign histomorphology does not exclude the possibility of clinically malignant behaviour. Our case study focuses on the comparative findings in a postmenopausal female diagnosed with an ovarian steroid tumour (not otherwise specified). A careful correlation between clinical and surgical evaluation and microscopic analysis is necessary, as is a regular followup.

OBJECTIVE To investigate the effects of drospirenone on nasal respiratory epithelium in postmenopausal women who are treated with hormone therapy (HT). DESIGN Thirty-five naturally postmenopausal women participated in the prospective study. Women received continuous-combined HT containing 1 mg 17beta-estradiol and 2 mg drospirenone. Cytological changes of nasal middle and inferior turbinate respiratory epithelium were evaluated by using the maturation index, performed at baseline and on the sixth cycle of HT. RESULTS Hematoxylin-eosin staining for the maturation index of the epithelial nasal cells of women reached better trophic aspects during 17beta-estradiol/drospirenone intake with respect to those observed at baseline (P < 0.001). The smears during HT emphasized the superficial and the intermediate types of cells, with a ratio index greater than 2. The parabasal cell content was less than 20%, and the karyopyknotic index showed degenerative changes in superficial and intermediate cells. CONCLUSIONS Our study confirmed that the nasal respiratory epithelium is an ovarian steroid target. Drospirenone acts on nasal cells similarly to other progestogens.

Purpose: Since, during the menstrual cycle, changes in neuronal activity and in auditory, olfactory, and taste thresholds were found, visual evoked potentials were investigated. Materials & Methods: In 50 healthy women the latency and the amplitude of P100 wave of pattern reversal visual evoked potentials were measured during the different menstrual phases (follicular, periovular, and luteal), as determined by sonography and serum progesterone level. Results: Compared with the follicular phase, during the luteal phase significant reduction in latency (101.29 ± 4.42 vs. 104.76 ± 5.02 ms, P < 0.01) and increase in amplitude (10.44 ± 3.15 vs. 8.62 ± 3.09 μ V, P < 0.05) were recorded. Conclusions: Fluctuations in ovarian steroid hormones affect the excitability of the visual system.

It is evident that complex biochemical interactions are involved in the regulation of myoma growth, and ovarian steroid hormones have significant influence on this process. Current myoma therapies manipulate the hormonal environment to achieve myoma regression and control of bleeding. Although several of these therapies achieve some level of success, further studies are necessary to evaluate the current and long-term effects of these therapies. In clinical medicine each patient must be evaluated thoroughly, and the decision for medical therapy or surgery--and for which medical therapy--needs to be individualized. If one medical therapy does not work, several other effective therapies are available.

Vasomotor symptoms (VMS), including hot flushes and night sweats, are the most common symptoms associated with menopause. Although the physiology of hot flushes is not fully defined, understanding the complex thermoregulatory circuitry that underlies VMS is important for the development of new therapies. This circuitry is composed of three distinct, yet interconnected, components: core body temperature, neurochemical messaging and peripheral vasculature. Evidence suggests that multiple physiological systems, including the neuroendocrine system, are important in the maintenance of thermoregulatory control. Causative roles of declining ovarian steroid levels in initiating thermoregulatory dysfunction are well documented. This paper reviews the physiology involved in the underlying thermoregulatory dysfunction that presumably causes VMS and discusses how this physiology relates to current and future VMS treatment options.

Die genetischen Hintergrunde des PCOS sind noch weitgehend ungeklart. Familienanalysen lassen uberwiegend einen autosomal-dominanten Hintergrund vermuten. Vor allem Gene der adrenalen und ovariellen Steroidbiosynthese sowie des Insulinstoffwechsels sind bezuglich ihres Zusammenhanges mit der Pathogenese des PCOS untersucht worden. Polymorphismen des CYP11A-Gens sind am ehesten mit PCOS assoziiert. Bei 20–30% der PCOS-Patientinnen mit pathologischem ACTH-Test finden sich Mutationen im CYP21B-Gen. Im Insulinstoffwechsel finden sich Varianten im Insulinrezeptorgen und im Gen des TNF-Rezeptors 2 mit dem PCOS assoziiert. Zusammenfassend liesen sich jedoch bisher keine eindeutigen und in unabhangigen Kollektiven reproduzierbare Befunde nachweisen, die fur den sicheren pathogenetischen Zusammenhang eines Kandidatengens mit dem PCOS sprechen. The genetic background of PCOS is still a matter of debate and widely unknown. Family studies show some correlation with an autosomal dominant pattern of inheritance. In particular, genes of adrenal and ovarian steroid biosynthesis and insulin metabolism have been extensively examined. There is good evidence for an association of polymorphisms of the CYP11A gene with PCOS. Furthermore, 20–30% of PCOS patients with a pathological ACTH test show mutations of the CYP21B gene. Concerning insulin metabolism, variations of the insulin receptor gene and the TNF receptor 2 gene have been described. However, today there is no definite proof for the existence of candidate genes for PCOS in groups of exactly defined and carefully analyzed PCOS patients.

To analyze the effects of treatments with GH and cyclic estrogen/progesterone (E/P) replacement on bone mineralization in patients with Turner's syndrome (TS), bone mineral density (BMD) was measured longitudinally. BMDs of the whole body and the lumbar spine in 16 adult female patients with TS (17-38 year old; 0-20 years by length of E/P treatment) were assessed using dual energy X-ray absorptiometry one to 5 times over a treatment period of up to 7 years maximum. GH treatment was performed in 9 cases (GH group), but not in the remaining 7 (non-GH group). E/P replacement therapy was initiated in all patients after they finished GH administration. The BMDs of both the whole body and the lumbar spine in the patients with TS were significantly less than those in age-matched normal subjects, and did not improve with E/P treatment. Although there were no differences in final body height and age at the beginning of E/P administration between the GH and non-GH groups, whole body BMD in the GH group was significantly lower than that in the non-GH group. These results indicate that GH administration in childhood and adolescence and E/P treatment in adulthood did not increase bone mineralization in the TS patients. Therefore, we can conclude that the optimal protocol of hormonal replacement therapy with GH and E/P during childhood and adolescence should be established as soon as possible.

The climacteric and menopause are characterized by erratic fluctuations and decline in ovarian steroid hormones that have broad impact on physical and psychological phenomena leading to a number of clinical syndromes encountered in primary care settings. This endocrine transition is abrupt in women and is not often adequately assessed using objective measures, leading to potential overuse of various medications to treat the physiological and psychological consequences of decline in ovarian hormones. This article reviews such issues and explains how primary care physicians may incorporate the endocrine changes more effectively in their evaluation and treatment of midlife women.

The risk factors, treatment regimens, and prognoses of many neurological diseases and injuries differ enormously between the sexes. Men and women differ in the timing of onset, severity, manifestation, and prognosis of a broad range of neurological and psychiatric disorders including neurodegenerative diseases, autism, attention deficit hyperactivity disorder (ADHD), schizophrenia, depressive disorders, Alzheimer's disease, and others. A combination of genetic, hormonal, and environmental factors undoubtedly contributes to these sex differences. This entry focuses on the roles of ovarian steroid hormones, especially estrogens and progesterone, and their contributions to women's neurological health. Sex steroids have widespread effects on normal neurobiological development and behavior, and they play roles in the manifestation and treatment of neurological dysfunctions. How hormones can have an impact on the physiology and behavior and change the responses to neurological injury and disease is becoming increasingly well understood and accepted through basic research and is applied to clinical practice.

A woman’s reproductive years are characterized by finely tuned waves of circulating sex hormones which are dictated by her menstrual cycle and in turn, influence many, if not all, of her physiological functions.

Introduction Primary amenorrhoea is rarely caused by androgen-producing tumours. Ovarian steroid cell tumour (SCT), not otherwise specified (NOS), is a rare type of sex cord-stromal tumour, accounting for less than 0.06% of all ovarian tumours (Hayes and Scully 1987). These tumours can produce steroids – especially testosterone – and may cause amenorrhoea, oligomenorrhoea and/or virilisation. Here we report the case of primary amenorrhoea caused by an androgen-producing SCT, NOS.

The goal of the gynecologist is to detect ovarian tumors in their earliest stages. Small virilizing tumors, which barely affect the size of the ovaries, are such lesions. Since the introduction of transvaginal sonography it is technically possible to detect small intraovarian neoplasms. Three cases of virilizing steroid cell tumors in postmenopausal women with ovarian volumes just exceeding the normal sizes for age are presented. High-frequency transvaginal ultrasound and color Doppler studies to measure flow parameters were used. These small tumors had different echogenicity from the surrounding ovarian tissue and two had low impedance-to-flow values. Gray-scale transvaginal sonography combined with color Doppler studies can make the diagnosis of small steroid cell tumors easier and, at times, better than other, more costly imaging modalities.

Ovarian steroid cell tumors, not otherwise specified (OSCTs), are extremely rare and present a diagnostic challenge when evaluating an ovarian mass. We present a case of such a tumor in a patient with known Congenital Adrenal Hyperplasia (CAH), secondary to 21-hydroxylase deficiency, who was noncompliant with her medications. The workup, diagnosis, and treatment of this rare condition are described.

Gynecology clinic-based studies have consistently demonstrated that induced hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced hypogonadism nor estradiol replacement influenced cognitive performance. Thus, the effects of induced hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman’s symptomatic experience during menopause. In this study, we examined the effects of induced hypogonadism and ovarian steroid replacement on cognitive performance in healthy premenopausal women. Ovarian suppression was induced with a GnRH agonist (Lupron) and then physiologic levels of estradiol and progesterone were reintroduced in 23 women. Cognitive tests were administered during each hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. With the exception of an improved performance on mental rotation during estradiol, we observed no significant effects of estradiol or progesterone on measures of attention, concentration, or memory compared with hypogonadism. In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short-term changes in gonadal steroids have a limited effect on cognition in young, healthy women. Differences in the clinical characteristics of the women receiving GnRH agonists could predict a risk for ovarian steroid-related changes in cognitive performance during induced, and possibly, natural menopause.

Radioimmunoassays were used to measure interictal levels of ovarian steroids (oestradiol, total oestrogens and progesterone) in migraine patients at the onset of menses and coincident with the luteinizing hormone surge preceding ovulation. Results of these verified bio-chemically-contrasting points of the ovarian cycle were used to compare 13 migraine patients without aura and 6 migraine patients with aura with 17 non-migraine women. No group differences were found for physiological basal levels of ovarian steroids measured at menses. Preceding ovulation elevation in oestradiol levels relative to normal was found in migraine patients with aura but not in migraine patients without aura. These results suggest that a variation in oestradiol levels is an important factor in the different clinical expressions of migraine.

The gap between the physician’s conviction that gonadal steroids mitigate the consequences of aging and the postmenopausal patient’s willingness to use hormonal replacement therapy (HRT) is widening. An explosion of information over the past decade indicates that estrogen is a growth and maintenance hormone which acts on virtually every organ and tissue in the body; among other things, it maintains the central nervous system’s plasticity, safeguards the stability of the coronary vasculature, and ensures the optimal mass and architecture of bone. Nevertheless, this information has had little impact on patients: only 15–20% of postmenopausal women use HRT [1]. Over 1/3 of patients who begin therapy discontinue it within a matter of months. Berman’s group surveyed over 2,000 women for two years and found that 20% had stopped their medication at 6 months, 38% by a year, 51% at 18 months and 59% by two years. Roughly 2.5–3.0 of women quit each month, in a steady rate of decline [2]. Reasons for this include a reluctance to continue menstrual periods, fear of cancer, and a reaction to the side effects of HRT, usually related to progestin rather than to estrogen.

Cocaine stimulates significant increases in luteinizing hormone (LH) and decreases prolactin levels in gonadally intact rhesus monkeys, but cocaine did not alter plasma levels of these anterior pituitary hormones in ovariectomized females. These findings suggested that ovarian steroid hormones may contribute to the endocrine effects of acute cocaine administration. To test this hypothesis, the acute effects of cocaine and placebo-cocaine on plasma LH and prolactin levels were examined in five ovariectomized rhesus females during three chronic hormone replacement conditions: 1) estradiol (E2beta) treatment (0.0015-0.006 mg/kg/day i.m.), 2) progesterone treatment (0.32 mg/kg/day i.m.), and 3) combinations of progesterone (0.32 mg/kg/day i.m.) and E2beta (0.002 and 0.004 mg/kg/day i.m.). Cocaine (0.8 mg/kg i.v.) did not alter prolactin or LH in ovariectomized monkeys without ovarian steroid replacement. During chronic estradiol treatment, cocaine produced an estradiol dose-dependent decrease in prolactin. Cocaine also decreased prolactin during treatment with progesterone alone and progesterone + E2beta (0.004 mg/kg/day i.m.). Cocaine stimulated a significant increase in LH during treatment with progesterone alone, but not during treatment with progesterone + E2beta, or three of four estradiol treatment doses. Cocaine pharmacokinetics did not differ as a function of hormone replacement conditions. Together, these data suggest that both E2beta and progesterone modulate cocaine's effects on prolactin, whereas E2beta alone and in combination with progesterone, do not facilitate LH release in response to cocaine in ovariectomized rhesus females.

Actions of estrogens in the walls of arteries have atherosclerotic-inhibiting and hemodynamic effects. Because others participating in this Symposium will be directly addressing the role of estrogens in preventing atherosclerotic cardiovascular disease, this presentation will focus on the hemodynamic effects of ovarian hormones.

The physiological role of catecholamines in the regulation of gonadotropin stimulated ovarian steroid secretion is unclear. This study was undertaken to investigate the influence of catecholamines on gonadotropin stimulated cultured human granulosa cells under serum-free conditions. Adrenaline and dopmine had no influence on LH stimulated estradiol production. Noradrenaline, however inhibited it (P

In 9 normally menstruating women undergoing surgical sterilization by tubal ligation the levels of a dozen steroids were measured in the blood from the peripheral and both ovarian veins before and after the enucleation of the largest follicle. In addition, the peripheral levels of progesterone, 17-hydroxyprogesterone, oestradiol and oestrone were measured during 3 pre-operative and 3 post-operative days. Compared to their levels in peripheral blood, the levels of pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, androstenedione, testosterone and oestradiol were significantly higher in the blood draining both ovaries, while those of oestrone were higher only in the blood draining the 'active' ovary (containing the largest follicle) and those of dehydroepiandrosterone and cortisol only in the blood draining the contralateral 'inactive' ovary. No differences were found as far as the levels of 20α-dihydroprogesterone and dihydrotestosterone are concerned. Furthermore, a comparison of the steroid levels in the blood draining the two ovaries revealed that the levels of oestradiol and oestrone were higher in the venous blood draining the 'active' ovary and those of dehydroepiandrosterone in the blood draining the 'inactive' one. Enucleation of the largest follicle resulted in the following changes: 1) A significant drop in the peripheral oestradiol levels which was associated with a significant rise in the levels of the other steroids studied, except those of androstenedione, testosterone and oestrone, which remained unchanged. 2) Decreased levels of oestradiol and oestrone and increased levels of dihydrotestosterone and cortisol in the venous blood draining the ovary that previously contained the largest follicle. 3) No differences were any longer found in steroid levels between the blood draining the two ovaries, with the exception of cortisol levels, which were higher in the blood originating from the 'inactive' ovary. 4) The levels of 17-hydroxyprogesterone, androstenedione, testosterone, oestradiol and oestrone were higher in the blood draining both ovaries when compared to their peripheral levels. 5) The peripheral levels of 17-hydroxyprogesterone, oestradiol and oestrone dropped to early follicular phase values within 24 h and remained at that level for at least 3 days. The results are interpreted as indicating that the principal secretory products of the largest follicle in vivo are oestradiol and oestrone. Moreover, both ovaries secrete 17-hydroxyprogesterone, androstenedione and testosterone and additional amounts of oestradiol, and most probably also some pregnenolone, 17-hydroxypregnenolone and progesterone. The relative contribution to the peripheral levels of 17-hydroxyprogesterone by the largest follicle as compared to that of other ovarian structures requires further investigation. It is emphasized that the stress associated with surgery gradually increases the secretion of a number of adrenal steroids, that may reach the ovaries in considerable quantities. This may render difficult the assessment of the effect of the enucleation of the largest follicle on the secretion of some steroids by the ovaries.

Ovariectomized rats that were 3–4, 12 or 22 months old were injected s.c. with 4 mg, of testosterone propionate and 3 days later were injected s.c. with 2.8 mg. progesterone or the oil vehicle. Blood samples were collected by heart puncture 5 hrs. later. Serum levels of LH and FSH decreased significantly as age increased. Progesterone significantly increased serum LH and FSH levels regardless of age. The increase in serum LH concentration attributed to progesterone was greatest in the young and least in the old rats. To determine if age effects were due to differences in pituitary response to GnRH, ovariectomized rats that were 2.5 to 23 months old were injected i.v. with GnRH at doses of 100 ng or 40 ng/100 g body weight or were primed with 25 mg progesterone and 50 μg estradiol-benzoate 3 days before an injection of 2 ng GnRH/100 g body weight. Blood was obtained by heart puncture before and 20 min. after GnRH. In each experiment serum LH levels significantly decreased with increasing age but were significantly elevated by GnRH. This increase in serum LH level in response to GnRH declined with increasing age. The data suggest that the elevation in serum LH level in response to GnRH declines as a result of aging in female rats and that this effect is independent of circulating ovarian steroid levels.

Ovarian stromal blood flow was measured by 133 xenon-clearance technique in five women before and immediately after abdominal hysterectomy preserving the adnexae. The interval between the two measurements ranged from 35 to 76 minutes. The rate of xenon clearance was reduced by 52 to 89 percent in four of the women who were in the fertile age and by 29 percent in one postmenopausal subject. These findings indicate that acute reductions in ovarian blood flow may be responsible for the postoperative transient drop in ovarian steroid levels in peripheral plasma reported earlier.

Administration of human chorionic gonadotropin (hCG) to promote ovarian steroid secretion near the time of recognition of pregnancy was evaluated. Neither 500 or 1000 IU of hCG caused a significant increase in luteal function as determined by progesterone (P(4)) concentrations in peripheral blood following treatment on Day 12. Estradiol concentrations were elevated (P

Dysfunctional uterine bleeding is a disorder which presents problems for effective treatment and management. We have utilized the ability of chronic LRH agonist treatment to suppress ovarian steroid production to examine its effects on stumptailed macaques with a detailed history of excessive days of menstrual bleeding. Five monkeys were treated for 6 months with daily injections of D-Ser[But]6 LRH (1–9) nonapeptideethylamide. This was successful in suppressing ovarian steroid production in all monkeys as indicated by the maintenance of serum concentrations of oestradiol at < 100 pg/ml and progesterone at < 1 ng/ml. All monkeys menstruated for their typical time period during the first treatment cycle, but thereafter bleeding stopped in 2 monkeys and was considerably reduced in a further 2. In the remaining monkey, no significant improvement occurred. The results indicate that suppression of ovarian function in this way may have a significant role to play in the treatment of dysfunctional uterine bleeding.

The daily injection of the anti-androgen, cyproterone acetate, into regularly laying hens failed to prevent ovulation immediately. The delayed response suggested that testosterone is not part of the ovarian positive feedback stimulus resulting from the presence of an ovulable follicle and leading to ovulation. Ovarian changes in treated birds, and their unimpaired response to LH-RH, suggested that the drug might be acting by altering ovarian steroid metabolism.