Ovaries In Postmenopausal Women Research Articles

DDX04+ Stem Cells in the Ovaries of Postmenopausal Women: Existence and Differentiation Potential.

Ovarian aging is a pacemaker with multiple organ dysfunction. Recently, stem cells with the ability to generate new oocytes have been identified, which provides the possibility of stem cell therapy for ovarian aging. Several studies have revealed the existence of stem cells in the human postmenopausal ovary. In this study, we describe a new method using magnetic-activated cell sorting combined with differential adhesion to isolate DDX4+ stem cells from ovaries of postmenopausal women and show that the cells exhibit similar gene expression profiles and growth characteristics with primitive germ cells. Furthermore, the DDX4+ stem cells could enter the meiosis stage and differentiation into oocytes. The RNA-seq data of the differentiated oocytes shows that mitochondrial metabolism may play an important role in the oogenesis process of the DDX4+ stem cells. Through using the human ovarian cortical fragments transplantation model, we indicated that the GFP-DDX4+ stem cells differentiated into some GFP positive oocyte-like structure in vivo. Our study provided a new method for the isolation of DDX4+ stem cells from the ovaries of postmenopausal women and confirmed the ability of these stem cells to differentiate into oocytes.

Quantification of Leydig cells and stromal hyperplasia in the postmenopausal ovary of women with endometrial carcinoma

Endometrioid endometrial carcinomas (EECs) are correlated with high serum levels of androgens and estrogen. We hypothesized that Leydig cells and ovarian stromal hyperplasia contribute to postmenopausal ovarian androgen production and are observed more frequently in EEC patients. Ovaries of postmenopausal women with EEC (n = 36) or non-endometrioid endometrial carcinoma (NEEC; n = 19) were examined for the presence of hilar Leydig cells and compared with ovaries resected for benign conditions (n = 22). Leydig cells were counted manually, and a Leydig cell density was calculated per millimeter squared hilar surface. Ovarian stromal hyperplasia was scored as atrophic, moderate hyperplastic, or marked hyperplastic. In all endometrial carcinomas, these findings were correlated with the serum levels of sex steroids and hormone receptor expression in their endometrial carcinomas. In EEC patients, mean number of Leydig cells was 282.8 cells compared with 76.3 cells in NEEC patients and 66.4 cells in controls. Leydig cells, marked stromal hyperplasia, and combined presence were observed more frequently in EEC patients compared with NEEC and controls. Combined presence was associated with higher serum sex steroid levels and increased tumor expression of estrogen and progesterone receptor. A cutoff value for Leydig cell hyperplasia could be proposed at a total of 300 Leydig cells bilaterally, examining a representative cross section of both hili. Concluding, we have quantified hilar Leydig cells and demonstrated that Leydig cells may contribute to the development of EEC by increased androgen production in postmenopausal women. The correlation between sex hormone levels and Leydig cell hyperplasia may support endometrial pathology screening in these women.

Serum glucose and insulin and risk of cancers of the breast, endometrium, and ovary in postmenopausal women.

Limited evidence suggests that hyperinsulinemia may contribute to the risk of breast, endometrial, and, possibly, ovarian cancer. The aim of this study was to assess the association of serum glucose and insulin with risk of these cancers in postmenopausal women, while taking into account potential confounding and modifying factors. We studied 21 103 women with fasting baseline insulin and glucose measurements in a subsample of the Women's Health Initiative. The subsample was composed of four studies within Women's Health Initiative with different selection and sampling strategies. Over a mean of 14.7 years of follow-up, 1185 breast cancer cases, 156 endometrial cancer cases, and 130 ovarian cancer cases were diagnosed. We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) by quartile of glucose or insulin. Serum insulin was positively associated with breast cancer risk (multivariable-adjusted HR for highest vs. lowest quartile 1.41, 95% CI: 1.16-1.72, Ptrend<0.0003), and glucose and insulin were associated with roughly a doubling of endometrial cancer risk (for glucose: HR: 2.00, 95% CI: 1.203.35, Ptrend=0.01; for insulin: HR: 2.39, 95% CI: 1.32-4.33, Ptrend=0.008). These associations remained unchanged or were slightly attenuated after mutual adjustment, adjustment for serum lipids, and assessment of possible reverse causation. Glucose and insulin showed no association with ovarian cancer. Our findings provide support for a role of insulin-related pathways in the etiology of cancers of the breast and endometrium. However, because of the unrepresentative nature of the sample, our results need confirmation in other populations.

Abstract B061: Association of leukocyte inhibitory immunoglobulin-like transcript 3 (ILT3) with ovarian cancer and prevention of its expression by dietary supplementation of Ashwagandha (Withania somnifera)

Abstract Background: Tumor-induced immunosuppression may be a reason for aggressive metastasis of ovarian cancer (OVCA). OVCA is a fatal malignancy of women with the highest case to death ratio among gynecological cancers. Most of the OVCA patients are postmenopausal women affected severely by the toxicity of current chemotherapeutics and danger of radiotherapy. Thus immunotherapy may be an alternative option for OVCA patients. Because OVCA mainly disseminates in the peritoneal cavity, immune functions in the tumor environment plays a crucial role in its progression. However, the mechanism(s) of immunosuppression by ovarian tumors are not well understood. Expression of leukocyte inhibitory immunoglobulin-like transcript 3 (ILT3, a member of inhibitory receptor family) by the tumors is one of the mechanisms in tumor-induced immunosuppression. Prevention or blocking of ILT3 expression may enhance anti-tumor immune responses. Information on ILT3 expression in OVCA and its prevention is not available. Herbs have long been used in traditional medicine against many human diseases including cancers. Ashwagandha or Winter Cherry (ASH, Withania somnifera), a herb known for its anti-tumor property, may enhance anti-tumor immunity by reducing ILT3 expression. Objectives: The goal of this study was to determine whether ovarian malignant tumors express ILT3 and whether dietary supplementation of ASH root powder reduces ILT3 expression in OVCA. Methods: Two experiments were performed. In the first one, archived specimen from normal ovaries of postmenopausal women (n=10), benign tumors (cystadenomas/adenofibromas, n=10) and ovarian malignant tumors (papillary serous) at early (n=7) and late stages (n=10) were examined for ILT3 expression. In the second group, laying hens, a preclinical model of spontaneous OVCA, were used. Healthy hens with normal ovaries or hens with early stage OVCA (selected by transvaginal ultrasound scanning) were divided into 3 groups and provided with basal diet (control) or diet supplemented with either 1% or 2% ASH root powder for 90 days. Each group had 20 hens (15 healthy, 5 with early stage OVCA). Hens were euthanized thereafter and gross morphology including normal and tumor stages were recorded, serum, ovarian tissues with or without cancer were collected and processed for ILT3 expression by immunohistochemistry (IHC), Western blotting or gene expression analysis. Differences in ILT3 expression among different pathological or supplemented groups were analyzed by one-way ANOVA and paired t-test for group-wise comparison. Results: Strong expression of ILT3 was detected in ovarian malignant tumors at early stage. A very weak or no expression of ILT3 was observed in normal ovaries, while it was weak to moderate for benign tumors. The expression was stronger as the OVCA progressed to late stages. Immunoblotting detected a band of approximately 55kDa. Similarities in the patterns of ILT3 expression was observed between OVCA hens and patients. As compared with untreated and 1% ASH-treated hens, tumor incidence and progression as well as ILT3 expression was decreased significantly in hens supplemented with 2% dietary ASH. Conclusions: The present study suggests that ILT3 is expressed by ovarian papillary serous cancers, and the expression of ILT3 increases with the progression of OVCA to late stages. Dietary supplementation of OVCA hens with 2% ASH reduced ILT3 expression and decreased the rate of tumor progression. Decrease in tumor progression was associated with the decrease in ILT3 expression. Thus ILT3 represents a potential target for enhancing the anti-tumor immune function in OVCA patients.ASH may be used to reduce ILT3 expression and prevention of OVCA progression. Support: Swim across America. Citation Format: Natasha Gupta, Sameer Sharma, Seby L. Edassery, Janice M. Bahr, Lindsey Franklin, Erika Paulsen, Pincas Bitterman, Animesh Barua. Association of leukocyte inhibitory immunoglobulin-like transcript 3 (ILT3) with ovarian cancer and prevention of its expression by dietary supplementation of Ashwagandha (Withania somnifera). [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B061.

Sclerosing Stromal Tumor of the Ovary in Postmenopausal Women: A Report of Two Cases

Sclerosing Stromal Tumor of the Ovary in Postmenopausal Women: A Report of Two Cases

Expression of gonadal steroid receptors in the ovaries of post-menopausal women with malignant or benign endometrial pathology: a pilot study

This pilot study aimed to investigate the expression of estrogen (ER) and progesterone receptors (PR), as well as their subtypes [alpha (ERα), beta (ERβ)], in the ovaries of postmenopausal women with benign or malignant endometrial pathology. Twenty postmenopausal women (age 66.2 ± 7.4 years) were included, diagnosed with benign (n = 10) or malignant [(serous/papillary (n = 4), endometrioid (n = 6)] endometrial lesions. Higher ERβ and PR ovarian expressions were observed comparing women with endometrioid versus non-endometrioid endometrial carcinoma (p = 0.022 and p = 0.029, respectively). Age, age at menarche and presence of hypertension were negatively associated with ERs and PR expression. The expression of ERα and ERβ was inversely correlated with menopausal age, which was not verified for PR. No significant association was observed between ERs or PR expression and benign or malignant endometrial pathology. Higher expression of ERβ and PR in the postmenopausal ovary is associated with the presence of a less aggressive type of endometrial cancer, comparing women with endometrioid versus non-endometrioid lesions. The expression pattern of ovarian receptors did not differ regarding the development of benign or malignant endometrial lesions. Larger observational studies are necessary to confirm the significance of our findings.

Sclerosing Sromal Tumor of the Ovary in Postmenopausal Women: A Report of Two Cases

Sclerosing stromal tumor (SST) was first delineated as a distinct ovarian sex cord stromal tumor in 1973 by Chalvardjian and Scully. It is a benign neoplasm, distinguished from other ovarian stromal tumors by the production of collagen and a pseudolobular pattern, and it tends to occur in the second and third decades of life in diagnosed patients. We discovered two rare cases of SST in post-menopausal women which are the topic of this report. These case studies are accompanied by a brief review of the literature.

Postmenopausal patients with endometrial cancer of type 1 have elevated serum estradiol levels in the ovarian vein.

Type 1 endometrial cancer (EC) is typically sex hormone sensitive; however, most women diagnosed with EC have already gone through menopause. Several studies have reported that the postmenopausal ovary is hormonally active, and estradiol (E2) production from the ovaries persists for as much as 10 years beyond menopause. The aim of this study was to evaluate whether sex steroid production from the ovaries contributes to the pathogenesis of type 1 EC. This was a prospective study of 53 women treated for EC (28 cases of type 1 disease and 25 cases of type 2 disease). Serum specimens were collected from the peripheral and ovarian veins of participants undergoing bilateral oophorectomy. The sex steroid hormone levels and hormonal milieu on cervical cytology were evaluated as maturation value (MV). In addition, the degree of stromal hyperplasia of the ovary was evaluated histologically. Although the E2 levels of the peripheral veins did not show any significant differences [8.2 (5.1-12.4) vs 7.4 (5.1-11.7) pg/mL, respectively; P < 0.05], the patients with type 1 EC had a higher E2 level in the ovarian vein than those with type 2 EC [25 (13.8-42.5) vs 15 (10.0-23.0) pg/mL, respectively; P < 0.05]. There were also no significant differences in the rate of moderate to marked hyperplasia of the ovarian stroma between the groups; however, the thickness of the ovarian cortex demonstrated a correlation with the ovarian E2 level. In addition, the MV displayed a strong correlation with the ovarian E2 level, but not the peripheral E2 level. The postmenopausal ovary is hormonally active, especially in patients with type 1 EC. The degree of ovarian stromal hyperplasia may (at least in part) contribute to the progression of type 1 EC, and MV may predict the level of E2 production from the ovaries in postmenopausal women.

Immunoexpression of aromatase cytochrome P450 and 17β-hydroxysteroid dehydrogenase in women's ovaries after menopause.

BackgroundMenopause results in a lack of regular menstrual cycles, leading to the reduction of estrogen production. On the other hand, ovarian androgen synthesis is still present at reduced levels and requires expression of several steroidogenic enzymes.MethodsThis study was performed on 104 postmenopausal women hospitalized due to uterine leiomyomas, endometriosis, and/or a prolapsed uterus. Patients were divided into three groups depending on the time from menopause. Group A patients experienced menopause 1–5 years before enrollment in the study (42 women). Group B included women who had their last menstruation 5–10 years before the study (40 women). Group C consisted of 22 women who were more than 10 years past menopause. Hysterectomy or removal of the uterine corpus with adnexa was performed during laparotomy. We evaluated the expression of aromatase cytochrome P450 (CYP 19) and 17β-hydroxysteroid dehydrogenase (17β HSD) by employing immunohistochemistry.ResultsActivity of 17β-HSD and CYP19 was demonstrated in the cytoplasm of stromal cells of postmenopausal ovaries, epithelium cells coating the ovaries, vascular endothelial cells, and epithelial inclusion cysts. However, overall expression of both 17β-HSD and CYP 19 decreased with time after menopause.ConclusionDemonstration of the activity of the key enzymes of ovarian steroidogenesis, CYP 19 and 17β-HSD, confirms steroidogenic activity in the ovaries of postmenopausal women. Nevertheless, ovarian steroidogenic activity decreases with time, and its significant decrease occurs 10 years after menopause.

CD24 and Nanog identify stem cells signature of ovarian epithelium and cysts that may develop to ovarian cancer

Ovarian cancer is the most lethal gynecological cancer. There is a general debate whether ovarian cancer is an intrinsic or an imported disease. We investigated whether in normal morphological appearance and in early stages of ovarian tumorgenesis typical cancer cell markers such as CD24 and Nanog are expressed. In 25% of normal appearing ovaries of post-menopausal women there was co-localization of CD24 and Nanog in the walls of the ovarian cysts, leaving the epithelial cells on the surface of these ovaries free of Nanog or CD24 expression. In benign ovarian tumors 37% of specimens were positive to CD24 and Nanog labeling while 26% of them were localized in the cyst walls. In contrast, in serous borderline tumors 79% specimens were labeled with CD24, 42% of them were localized in cysts and in 32% of them showed co-localization with CD24 and Nanog was evident: the rest were labeled in the ovarian epithelial cells. In serous ovarian carcinomas 81% specimens were labeled with CD24 antibodies. In 45% of them co-localization with Nanog was evident in the bulk of the cancerous tissue. In mucinous carcinomas no labeling with CD24 or Nanog was evident. In view of the synergistic effect of CD24 and Nanog expressed in malignant cancer development in other systems, it is suggested that such an analysis can be valuable for early detection of ovarian cancer. Moreover, the abundance of these markers in cysts in the development of ovarian cancer may suggest that they present an intrinsic source of the development of the highly malignant disease. Finally, since CD24 is exposed on the surface of the cancer cells, it may be highly beneficial to target these cells with antibodies to CD24 conjugated to cytotoxic drugs for more efficient treatment of this malignant disease.

Hormone concentrations in the homogenates of ovarian tissue and blood serum in postmenopausal women not using hormone therapy

Ovaries in postmenopausal women synthesize steroids, mostly androgens. Removal of the ovaries after menopause may be reflected by menopausal symptoms and arterial hypertension observed during postoperative period, along with a significantly increased risk of death due to cardiovascular complications. It is not understood if the clinical consequences of gonad removal at different time points after menopause are similar. The aim of this study was to evaluate ovarian steroidogenesis and consequently to define the role of the ovaries in postmenopausal women depending on the time after menopause. Concentrations of hormones were determined in ovarian homogenates and serum of postmenopausal women. This study included 207 postmenopausal women. They were divided into groups depending on the time after menopause. All participants had laparotomic removal of the ovaries. Concentrations of estradiol, testosterone and androstenedione were measured in ovarian homogenate and serum. The study revealed that ovarian homogenate and serum concentrations of estradiol, testosterone and androstenedione were the highest in women up to 5 years after menopause and since then significantly decreased. This study showed that testosterone, androstenedione and estradiol are synthesized in the postmenopausal ovaries. The peak synthesis of these hormones occurs up to 5 years after menopause and significantly decreases thereafter.

The RANZCOG College Statement on prophylactic oophorectomy in older women undergoing hysterectomy for benign disease: Is the evidence sufficient to change practice?

In 2009, the Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) published College Statement C-Gyn 25: "Prophylactic oophorectomy at the time of hysterectomy for benign gynaecological disease, which recommended that caution should be exercised in performing bilateral salpingo-oophorectomy (BSO) at the time of hysterectomy for benign disease in women younger than 65 years of age." The aims of the study were to assess current practice with regard to prophylactic oophorectomy in this setting and to assess knowledge about the College Statement. We also sought to review the evidence behind the Statement. An anonymous email survey of all consultant gynaecologists and gynaecology registrars in Sydney West Area Health Service (SWAHS) was conducted. The response rate was 52%. The survey found that there was an increasing tendency to remove ovaries with increasing patient age, and over 60% of gynaecologists would routinely recommend removal of ovaries during a hysterectomy for benign disease in a 60 year old woman. The survey also revealed a lack of knowledge as to the existence or content of the College Statement. A review of the literature found that evidence suggesting benefit in retention of ovaries in postmenopausal women has been extrapolated from a modelling study, observational studies or from data on premenopausal oophorectomy. A survey of gynaecologists revealed that few currently appear to adhere to the College Statement regarding prophylactic oophorectomy at the time of hysterectomy for benign disease. High quality evidence regarding either harm or benefit following retention of ovaries after menopause is lacking. Nevertheless, dialogue between clinicians and patients on this topic is important.

Immunohistochemical analysis of steroid receptors in ovaries of postmenopausal women--effects of aging and hormone status.

Current knowledge on immunolocalization and immunoexpression of steroid hormone receptors, especially estrogen receptor alpha (ER-alpha), progesterone receptor (PR) and androgen receptor (AR) in normal ovaries in postmenopausal women is not complete. The recognition of localization of these receptors in postmenopausal women is crucial, as many of these women receive estro-progestagene therapy, and its participation in the pathogenesis of ovarian cancer should be carefully studied. In our paper we present the results of immunohistochemical studies performed on samples from 100 post-menopausal women (aged: 48 to 60 years) who did not use hormonal therapy. The ovaries were removed during elective operation due to uterine leiomyoma, endometriosis and/or prolapsed uterine. PR, ER-alpha and AR were detected in the normal ovaries of postmenopausal women in stroma and in ovarian surface epithelium, as well as in its invagination and in epithelial inclusion cysts. The expression of PR and AR did not change, while the expression of ER-alpha decreased in time from menopause, and it was also detected in patients more than 10 years after menopause. Women older than 60 were not included in the study. The concentration of selected hormones was measured in the serum. The immunohistochemical expression of PR and AR were similar in all examined patients and did not correlate with FSH, LH, T, A, DHEAS concentrations in serum, while immunohistochemical expression of ER-alpha correlated with FSH, LH, T, A, DHEAS concentrations in serum. The significant correlation of decreasing expression of ER-alpha in normal ovarian tissue and decreasing concentrations of T, A and DHEAS in serum were found, as well as increasing serum concentrations of FSH and LH.

Androgen Co-therapy In Menopause

Menopause is associated with various hormonal changes, including androgen deficiency. This review discusses the place of androgen therapy in the management of menopause, including the pitfalls in diagnosis, the confusion surrounding androgen prescription, and the reasons behind this controversy. HORMONAL CHANGES IN MENOPAUSE Menopause is associated with a variety of endocrine changes (1). These lead to a reduction in sexuality and well-being (2). The changes include: Decline in growth hormone. This begins prior to 1. ovarian failure, and is a normal part of life. It is accelerated during peri-menopause, and itself may accelerate ovarian failure. Fibrosis of thyroid gland, and a decline in serum 2. T3 of 25% to 40%, though most post menopausal women remain clinically euthyroid. Reduction in estrogen levels, with the predominant 3. estrogen being the less potent estrone, derived from peripheral conversion of androstenedione in the liver, fat and some hypothalamic nuclei. Fall in serum DHEA and DHEAS levels, which are 4. greater in women than men, and may be due to the relative estrogen deprivation. Decline in androgen production. The production of 5. the predominant androgen, androstenedione, declines from 1500 to 800pg/ml, with only 20% being contributed by the ovary in post menopausal women. Post menopausal testosterone levels are also lower 6. than those in premenopausal women, with the decline beginning around age 30.Testosterone levels at age 40 are half those at age 21. At menopause, a 15% decline occurs in testosterone and androstenedione. Dihydrotestosterone, the most potent of 7. endogenous androgens, decreases by 44% between the third and eighth decade. This decline is associated with reductions in metabolic concentrations.

The presence and role of progesterone receptor in the ovaries of postmenopausal women who have not applied hormone replacement therapy.

At present, not much is known about progesterone receptor (PR) expression and localization in postmenopausal women ovaries. In the ovaries of reproductive age women, PR is localized in internal theca and granulosa cells, corpus luteum, ovary surface epithelium (OSE) and in stroma. PR expression depends on the serum concentration of progesterone, estrogen, gonadotropin and androgen. The goal of the conducted studies was to examine PR localization and expression in the ovaries of postmenopausal women who have not applied hormone replacement therapy so far. Also, the correlation was examined between PR expression and localization in the ovaries, steroid and gonadotropin hormone serum concentrations, and influence of the time from the last menstruation. The material came from 50 postmenopausal women who had their ovaries removed due to non-neoplastic diseases. The women were divided into 3 groups (A, B, C) depending on the time from the last menstruation. The follitropin (FSH), luteotropin (LH), estradiol (E2), testosterone (T), androstendione (A) and dehydroepiandrosterone sulphate (DHEAS) concentrations in blood plasma were measured. Monoclonal mouse anti-human PR antibody was used for immunohistochemical detection (examination involved 50 postmenopausal ovaries). Between particular groups, E2 serum concentrations did not differ, but FSH, LH, T, A, DHEAS serum concentrations were significantly different. Immunohistochemical nuclear localization of PR in postmenopausal women ovaries was observed. PR expression was similar in all three groups (A, B, C). PR expression was observed in OSE nuclei and invaginations cysts deriving from the isolation of invaginated epithelium and metaplastic columnar epithelium and in stroma. In the ovaries of postmenopausal women who have not applied hormone replacement therapy so far, PR was detected in all three groups. Its expression did not depend on the time from menopause and was similar in all examined groups. FSH, LH, T, A, DHEAS serum concentrations did not influence PR expression.

The presence and role of progesterone receptor in the ovaries of postmenopausal women who have not applied hormone replacement therapy.

The presence and role of progesterone receptor in the ovaries of postmenopausal women who have not applied hormone replacement therapy.

ANDROGENIC CAPACITY OF THE FOLLICLE-DEPLETED OVARY IN VCD-TREATED MICE

One unresolved question related to residual ovarian tissue in postmenopausal women is whether it retains steroidogenic capacity and produces androgens. Moreover, contributions of this tissue to the physiology of post-menopausal women have not been determined. An ovary-intact mouse model of natural menopause has been developed using the chemical 4-vinylcyclohexene diepoxide (VCD). Daily dosing of mice and rats with VCD selectively destroys ovarian primordial and primary follicles by accelerating the normal process of atresia. When given at a high dose, VCD causes early ovarian failure in mice. Because remaining larger follicles are not directly affected, the animal ovulates normally, progresses gradually into ovarian failure and retains residual ovarian tissue. Thus, the VCD-treated mouse is a relevant model for studying the follicle-depleted ovary and its potential impact on post-menopausal women's health. The purpose of this study was to characterize the capacity of residual ovarian tissue in the VCD-treated follicle-depleted mouse. Female B6C3F1 mice (28-days old) were dosed daily with either VCD or sesame oil (vehicle control) for 20 days. Vaginal cytology was performed daily to monitor estrous cyclicity of each animal and assign ovarian failure in the treatment group. Ovaries were collected on d120 or d181 after the onset of dosing. Expression of mRNA encoding low density lipoprotein receptor (LDLR), cholesterol side chain cleavage enzyme (Cyp11a) and 17alpha-hydroxylase (Cyp17) was determined by real-time PCR. Expression of oocyte-specific genes Zygote arrest 1 (Zar1) and Zona pellucida glycoprotein 3 (Zp3) was used as a negative control for follicledepleted ovaries. Relative to cycling controls, residual ovarian tissue in VCD-treated animals was highly enriched (ratio VCD-treated/cycling controls, P<0.05) in mRNA encoding LDLR (d120, 1.83 ± 0.03; d181 5.31 ± 0.11), Cyp11a (d120, 1.55 ± 0.29; d181, 2.48 ± 0.25) and Cyp17 (d120, 114.63 ± 0.30; d181, 147.71 ± 0.14). Conversely, mRNAs encoding the oocyte-specific genes Zar1 and Zp3 were undetectable in all follicledepleted ovaries. Circulating levels of androstenedione were measured at selected time points during the period following the onset of dosing. On most of the time points measured there was no difference (P>0.05) in circulating androstenedione between groups (range 0.15-1.16ng/ml). At the d120 time point circulating androstenedione levels were lower (P<0.05) in VCD-treated animals (0.30 ± 0.13 ng/ml); whereas, on d181 there was no difference (control, 0.15 ± 0.048; VCD, 0.32 ± 0.10 ng/ml). These data support that residual ovarian tissue in the follicle-depleted mouse retains the capacity to synthesize and secrete androgenic steroids. Further, this study demonstrates that the VCD-treated mouse model of menopause may be relevant for understanding physiological contributions of the ovary in post-menopausal women. (AG021948) (poster)

Transvaginal color Doppler sonographic assessment of uterus and ovaries in postmenopausal women: The effect of local estrogen treatment

Objective The objective was to evaluate the effect of local estrogen treatment on the uterus and ovaries using transvaginal color Doppler sonography. Materials and methods A 12-week randomized open-label study of postmenopausal women taking local estrogen treatment and controls was conducted. The study group was treated with either a 25-μm estradiol vaginal tablet or 1 g of conjugated estrogen cream intravaginally each day for 2 weeks followed by twice a week for 10 weeks. The control group did not receive any type of hormone replacement therapy. All women underwent transvaginal ultrasonography and color Doppler imaging of the uterine arteries both before starting local estrogen treatment and after treatment. The uterine volume, ovarian volume, endometrial thickness, and uterine arterial blood flow of the two groups were evaluated. Statistical analysis was performed using paired and unpaired Student's t-test. A p value of <0.05 was considered statistically significant. Results Of the 53 postmenopausal women recruited to this study, 26 women received local estrogen treatment for treatment of urogenital symptoms and 27 untreated women constituted the control group. The mean age was 54.85 ± 5.51 years. The uterine and ovarian volumes were not significantly different before and after treatment in either of the groups. The endometrial thickness did not change in the local estrogen treatment group (4.00 ± 1.60 and 4.30 ± 1.20 mm) or in the control group (3.90 ± 1.40 and 3.70 ± 1.50 mm). The mean resistance indices in the local estrogen treatment group before and after treatment (1.01 ± 0.10 and 0.96 ± 0.10) were not significantly different from those of the control group (0.96 ± 0.15 and 0.97 ± 0.10). The mean pulsatility index after 12 weeks of treatment was lower than before treatment, although not statistically significantly (3.69 ± 1.32 and 4.27 ± 1.49; p > 0.05), and the mean pulsatility indices did not differ between the study and the control groups. Conclusion The volumes of the uterus and the ovaries, including endometrial thickness, were not affected and did not show any significant influence of the 12-week local estrogen treatment. The uterine arterial blood flow did not significantly change after treatment.

Hormonal function after ovarian transposition to the abdominal subcutaneous fat tissue

We previously reported a new technique for ovarian transposition to the abdominal subcutaneous fat tissue (OTAFT) following hysterectomy. The purpose of this study is to assess the hormonal function after OTAFT. From 1993 to 2000, OTAFT was performed in 27 patients (group A). Forty-two women underwent hysterectomy and retained ovaries without transposition (group B). In 19 cases, bilateral oophorectomy with hysterectomy was performed, and they received a hormone replacement therapy (HRT) (group C). Serum follicle-stimulating hormone (FSH) level of patients was monitored every 2-12 months, and the time of menopause (defined as FSH >40 mIU/mL two times consecutively) was determined in groups A and B. After a median follow-up of 65 months, cumulative ovarian survival did not show significant difference between group A and group B (HR = 0.52, 95% CI = 0.17-1.16; P= 0.10). In patients who were 40 years old or younger, ovarian function declined significantly in group A compared to group B (HR = 0.29, 95% CI = 0.02-0.91; P= 0.04). However, FSH level of postmenopausal patients in group A was not different from FSH level of patients in group C, but FSH level of postmenopausal patients in group B was significantly higher than FSH level of patients in group C (P= 0.002). Although the procedure of OTAFT may somewhat affect the ovarian function, the transposed ovary in postmenopausal women presumably still secrete a small amount of estrogen which is equivalent to an estrogen level by HRT.

FSH and LH responses to GnRH after ovariectomy in postmenopausal women.

Whether the postmenopausal ovary is still playing a role in the control of gonadotrophin secretion in response to GnRH has not been investigated. The aim of the present study was to test this hypothesis by examining changes in basal and GnRH-induced gonadotrophin secretion in postmenopausal women after bilateral ovariectomy. The responses of LH and FSH to GnRH [10 microg intravenously (i.v.)] were investigated in postmenopausal women from 2 days before to 8 days after total abdominal hysterectomy plus bilateral ovariectomy. Nine postmenopausal women aged 52-67 years and between 5 and 15 years after menopause. In all cases the ovaries were histologically normal. Pituitary responses to GnRH were calculated every 12-24 h as the net increases in LH (DeltaLH) and FSH (DeltaFSH) at 30 min above the basal values. Basal values of oestradiol (E2) and testosterone were also measured. Basal values of FSH showed a significant decrease on postoperative days 2 (P < 0.01) and 8 (P = 0.03) as compared to day 0, while at the same time points after the operation LH values were marginally lower than on day 2 (P = 0.05). Serum E2 values showed a gradual increase up to postoperative day 1 (P = 0.04) and a gradual decline thereafter. Basal testosterone concentrations decreased gradually and significantly after ovariectomy and were significantly lower on day 8 than on day 0 (P < 0.01). DeltaFSH and DeltaLH responses to GnRH did not change significantly with time. A temporary increase at 12 h after the operation was not significant. These results demonstrate for the first time that the removal of the ovaries in postmenopausal women does not affect GnRH-induced gonadotrophin secretion in the short term. It is suggested that the postmenopausal ovary is not a dominant regulator of hypothalamic-pituitary interactions.