Exogenous Estrogen Administration Research Articles

Chronic 17β-estradiol pretreatment and ischemia-induced hippocampal degeneration and memory impairments: A 6-month survival study

Exogenous administration of estrogen has been shown to significantly reduce ischemia-induced neuronal degeneration. However, the long-term impact of such treatment on neuronal protection and functional recovery remain largely unknown. The present study assessed the effects of a 15-day pretreatment with 17β-estradiol on memory deficits and neuronal damage up to 6 months following a 10-min global ischemia in rats. Four groups of ovariectomized female rats [sham-operated and ischemic rats receiving a 15-day pretreatment of either the vehicle or 17β-estradiol (100 μg/kg)] were tested. The 8-arm radial maze and object recognition tests served to evaluate the impact of 17β-estradiol treatment on ischemia-induced spatial and recognition memory impairments, respectively. Testing in the radial maze was initiated at two distinct time intervals following reperfusion (7 and 120 days) to evaluate changes in memory functions over time. Our findings revealed long-lasting neuroprotective effects of 17β-estradiol treatment on hippocampal CA1 pyramidal cells in ovariectomized ischemic rats (43.5% greater neuronal survival than observed in vehicle-treated ischemic animals). Importantly, this neuronal protection translated into significant improvements of recognition and spatial memory functions in estradiol-treated ischemic rats.

Androgen Modulates Thymopoiesis by Regulating Thymocyte Precursor Immigration.

Impaired thymopoiesis contributes to immune deficiency in aging, AIDS, and following allogeneic bone marrow transplantation. However, little is known of the mechanisms of thymic regulation and the determinants of thymic function. Exogenous administration of testosterone and estrogen has been shown to accelerate thymic involution. Conversely, studies have demonstrated that castration of male mice resulted in increased thymic size and thymocyte number. We present data that thymic enlargement in castrated male mice is due to enhanced thymopoiesis. Comparing castrated post-pubertal male mice with age-matched control littermates, we found a statistically significant doubling of thymic weight, thymocyte number, and double-positive CD4+CD8+ thymocytes as early as eight days post-orchiectomy. Major thymocyte subsets defined as CD4− CD8−, CD4+CD8−, CD8+CD4− were also increased post castration and the ratio of subsets was unchanged suggesting that castration augmented overall thymic activity. This was further corroborated by a concomitant 4–6 fold increase in thymic T cell-receptor excision circles (TREC). Significantly, at one month post-castration, early thymic progenitors (Lin- CKIT hi CD44 hi) were increased threefold in the castrated cohort. The increase in thymic productivity led to a subsequent increase in peripheral cell populations, with a significant increase in splenic CD4+ and CD8+ T cells. The greatest proportion of this increase was due to naïve splenic CD4 and CD8 T cells total numbers as defined by CD44lo expression. Memory splenocytes, CD44hi CD4+ and CD8+ cells, were slightly increased as well. Additionally, there was an increase in the number of splenic recent thymic emigrants (RTE) as enumerated by TREC. Our data suggest that androgen withdrawal leads to an increase in thymopoiesis, as enumerated by a significant influx of ETPs, increased total thymic TREC, subsequent increases in single positive thymocytes, and increased peripheral recent thymic emigrants. Furthermore, the data suggest that a mechanism by which this occurs is through increased immigration of thymocyte precursors from the bone marrow into the thymus identifying this as a central point in thymic regulation.

Localization of Eutr2, a locus controlling susceptibility to DES-induced uterine inflammation and pyometritis, to RNO5 using a congenic rat strain

In some rat strains chronic administration of exogenous estrogens induces pyometritis, an inflammation of the uterus associated with infection, suggesting that there is genetic variation in susceptibility to estrogen-induced inflammation and pyometritis. In this article we report that following 10 weeks of treatment with the synthetic estrogen diethylstilbestrol (DES), Fisher 344 (F344) rats exhibit modest uterine inflammation and a 0% incidence of pyometritis. By contrast, under identical experimental conditions, Brown Norway (BN) rats exhibit significant inflammation and a 100% incidence of pyometritis. Similarly, we also observed profound uterine inflammation and a 100% incidence of pyometritis in a congenic rat strain in which a segment of RNO5 from the BN strain is carried on the F344 strain. These data suggest that a locus on RNO5 controls both the magnitude of DES-induced uterine inflammation and susceptibility to DES-induced pyometritis. This locus, designated Eutr2, resides within the same segment of RNO5 as the Eutr1 locus, which confers susceptibility to E2-induced pyometritis in an F2 population generated in a cross between the BN and August x Copenhagen 9935, Irish (ACI) strains.

Estrogenic effects of 17β-aminoestrogens assessed in uteri of rats and mice

Administration of exogenous estrogens has been associated with an increase of thromboembolic events. The 17β-aminoestrogens produce anticoagulant effects contrasting with the procoagulant effects of the natural occurring estradiol in rodents. This work compares the estrogenic effects induced by 17β-aminoestrogens prolame, butolame, pentolame, and estradiol in vivo models. Dose–response curves were performed using immature CD1 mice and Wistar rats. The animals were injected with estradiol or 17β-aminoestrogens (0.01 to 1000 μg/kg), or vehicle. The uterine wet and dry weights were determined. The 17β-aminoestrogens increased uterine weight in a dose-dependent manner. The uterotrophic effect produced by estradiol induced lower ED 50 (6.5 and 4 μg/kg) and higher E max values (+523–350%) in mice as compared with those from the rat, indicating more susceptibility of the mice model. The 17β-aminoestrogens are partial estrogenic agonists with a relative uterotrophic effect of estradiol (100%) from 9–86%. Only the ED 50 values of 17β-aminoestrogens in CD1 mice showed a direct correlation to the length of the amine group substitution in C-17 since their efficacy and potency were in the order: prolame>butolame>pentolame.

Simultaneous Increases of Leptin and Gonadotropin-Releasing Hormone Following Exogenous Estrogen Administration in Women with Normally Menstrual Cycle

The aim of this study was to investigate whether administration of exogenous estrogen affects the changes of leptin and GnRH levels in women with normal menstrual cycle. A total of 18 women received a bolus intravenous injection of 20 mg conjugated estrogen (premarin group) at 0800 during the fifth day of menstrual cycle, while another 18 women were administered 20 mL of normal saline as the control group. Fasting blood samples were collected at 0, 4, 8, 24, 28, 32, 48, 56, 72 and 96 hours after injection for analyses of leptin, GnRH, estrone (E(1)), estradiol (E(2)), LH and FSH. Both the mean plasma levels of E(1) and E(2) were significantly increased from 4 hours and significantly sustained elevated levels up to 72 hours after injection of premarin. Simultaneous significant increases of leptin and GnRH levels were observed at 28, 32 and 48 hours after injection, while the controls remained constant. The mean LH and FSH levels were initially suppressed and then significantly increased at 56 and 72 hours after premarin administration. Leptin appears to be involved in the regulation of positive feedback mechanism of estrogen by conveyance of metabolic signal to affect the release of GnRH in hypothalamus, while its participation in the modulation of negative feedback remains unknown.

Estrogen Attenuates Early Carotid Artery Injury-Induced Inflammation

Background Inflammation plays an important role in the response to endoluminal vascular injury. Estrogen (17B-estradiol, E2) inhibits neointima formation in animal models and the progestin medroxyprogesterone acetate (MPA) blocks this effect. Hypothesis: Perivascular inflammation as measured by leukocyte infiltration and expression of adhesion molecules/chemokines/ cytokines is modulated by exogenous estrogen administration in the balloon injury model of the rat carotid artery. Methods and Results Ovariectomized (OVX) rats were randomly divided into subgroups and treated with E2, medroxyprogesterone acetate (MPA), E2+MPA, or vehicle (V) and subjected to balloon injury of the right carotid artery. After 24 hours, rats were euthanized and carotid arteries (injured and control) were analyzed for inflammatory cells by flow cytometry. Granulocytes and monocyte/macrophages were increased 26-fold and 12-fold, respectively, in injured compared to contralateral control arteries of vehicle treated rats. E2 reduced the granulocyte and monocyte/ macrophage populations of injured vessels by ~ 50% and increased T-lymphocytes, while MPA had no independent effect on inflammatory cells but completely blocked the E2 effect. Immunohistochemical examination verified these findings and localized inflammatory cells to the adventitial and periadventitial domains of injured vessels. To evaluate the early effects of estrogen on targets of inflammatory signaling, carotid arteries from both OVX+V and OVX+E2 rats were homogenized 2 hours after injury and RNA was isolated. Quantitative real-time RT-PCR revealed marked injury-induced mRNA expression upregulation of adhesion molecules (P-selectin, VCAM-1, ICAM-1), chemoattractants (MCP-1, CINC-2) and cytokines (IL-1, IL-6 and TNF- α ) with estrogenic attenuation of this injury effect. ELISA and protein array studies from homogenized OVX+V and OVX+E2 rat carotid arteries 6 hours after injury confirm upregulation of inflammatory mediators with estrogen blunting this injury-induced response. Conclusion Estrogen attenuates neointimal formation after vascular injury, at least in part, by modulating pro-inflammatory mediator expression and by limiting leukocyte entry from adventitial tissues into injured vessels early in the injury response.

Stroke-induced changes in estrogen release and neuronal activity in the parabrachial nucleus of the male rat

Recent investigations have provided evidence to suggest exogenous estrogen administration into autonomic nuclei prevents or reverses the autonomic dysfunction observed after middle cerebral artery occlusion (MCAO) in male rats. Because estrogen seems to be a potent neuroprotectant against autonomic dysfunction, it is our hypothesis that endogenous estrogen levels within autonomic nuclei will increase in response to stroke. Therefore, in this investigation, in vivo microdialysis was used to simultaneously measure the concentration of estrogen in the plasma and in the parabrachial nucleus (PBN) of male Sprague-Dawley rats after MCAO. Analysis of dialysate samples before MCAO and in sham-operated controls revealed a baseline concentration of estrogen in the PBN (38 ± 3 pg/mL; n = 36), which was significantly greater than that found in plasma (22 ± 6 pg/mL; n = 6; P < .05). The concentration of estrogen in the PBN was significantly increased immediately after MCAO (85 ± 4 pg/mL; n = 7; P < .05) but then decreased to below pre-MCAO values (12 ± 2 pg/mL; n = 7; P < .05) by 90 minutes after MCAO and remained below baseline levels until the end of the experiment (240 minutes post-MCAO). No changes in plasma estrogen levels were detected at any time point after MCAO. In addition, extracellular electrophysiological recordings from PBN neurons revealed that MCAO resulted in an immediate decrease in the activity of PBN neurons, which was completely blocked after systemic estrogen injection. These results suggest that estrogen is released into the PBN in response to MCAO and that the source of estrogen seems to be primarily caused by terminal release as opposed to increased local synthesis.

Enhancing the fertility of poor responders by treatment with estrogen rebound combined with a short protocol.

Aim: To assess the efficacy of estrogen rebound (ER) plus flare-up by gonadotropin releasing hormone agonist (GnRH-a) in poor responders who failed to become pregnant prior to a long protocol treatment. Methods: The patients comprised of thirty-one infertile patients with oocyte retrieval levels of less than five, who had undergone several long protocol treatment cycles. The efficacy of treatment with the ER plus flare-up from GnRH-a was compared with the prior long protocol treatment. The main outcome measures are: confirmation of ER, maximal serum E2 levels prior to human chorionic gonadotropin (hCG) administration, follicular development, dose, and duration of gonadotrophins in a clinical setting. Results: The ER was confirmed by estrogen levels; FSH increased with ER plus flare-up from GnRH-a. Although the 31 patients included in the study had undergone frequent prior treatment cycles, including the long protocol, the pregnancy rate per embryo transfer following ER plus flare-up by GnRH-a was 37.5% (nine of 24). The number of follicles, number of oocytes retrieved, and the E2 level was higher than those found in prior treatment cycles. Conclusion: Exogenous estrogen administration with PremarinR plus flare-up by GnRH-a may represent an alternative and effective protocol for poor responder patients who had previously undergone several prior long protocol treatments. (Reprod Med Biol 2003; 2: 127-131).

Hormone replacement therapy: current controversies.

Postmenopausal hormonal therapy is used to manage the climacteric symptoms that impair the quality of life of a substantial number of women. The difficulty is achieving the desired effects with minimal side-effects and no adverse health risks. Fundamental to this is understanding the physiology of oestrogen in women and the metabolism of the therapeutic compounds. Although the effects of oral oestrogen therapy have been studied extensively, there is insufficient evidence to assess adequately the independent effects of progestin use, other oestrogen compounds, differing doses and duration of treatment. We have reviewed some basic concepts of oestrogen physiology and how these relate to exogenous oestrogen administration, the risks of greatest concern, and the role of androgens and newer treatment alternatives.

Vasomotor and vascular effects of hormone replacement therapy

Cardiovascular risk factors impair endothelium-dependent vasodilation as well as other functions of the endothelium, thereby predisposing the patient to atherosclerosis and its overt clinical manifestations. Loss of endogenous estrogen also leads to reduced bioavailability of endothelium-derived nitric oxide. In premenopausal women, the impairment of endothelial function develops within 1 month of surgical ovariectomy and is reversed by the administration of exogenous 17β-estradiol. Exogenous estrogen administration restores endothelial function by enhancing nitric oxide synthesis through genomic and nongenomic mechanisms and by reducing oxidative stress and nitric oxide breakdown. The effect of progesterone on endothelial function is still under investigation. In animal studies, medroxyprogesterone acetate (MPA) counteracts estrogen’s beneficial effects on endothelial function and on coronary plaque size. In humans, however, the addition of progesterone to estradiol does not appreciably attenuate estrogen-associated endothelium-dependent vasodilation. Secondary prevention trials with conjugated equine estrogen plus MPA have no proven benefit in reducing coronary events, progression of angiographic coronary atherosclerosis, or incidence of cerebrovascular events. This suggests that beneficial effects of estrogen on endothelial function are counterbalanced by detrimental effects, perhaps because of proinflammatory and prothrombotic actions. The selective estrogen receptor modulators are currently under investigation as agents that might retain the favorable, without possessing the unfavorable, effects of estrogen on the vascular system.

Overview of gender aspects of cardiac syndrome X.

Cardiac syndrome X, a condition defined by the presence of angina-like chest pain, a positive response to stress testing and normal coronary arteriograms, has been shown to occur in approximately 20--30% of angina patients undergoing coronary arteriography. The prevalence of syndrome X is significantly higher in women compared to men. In the majority of patients with chest pain and normal coronary arteriograms, symptoms are likely to be non-cardiac in origin. However, myocardial ischaemia may be the pathogenic mechanism in a proportion of syndrome X patients. Indeed, the clinical characteristics, the ischaemic electrocardiographic findings and the presence of myocardial perfusion defects during stress testing are similar in syndrome X and coronary artery disease patients. Moreover, coronary sinus oxygen saturation abnormalities and pH changes, as well as myocardial lactate production and alterations of cardiac high energy phosphate are seen during stress testing in patients with syndrome X and appear to endorse an ischaemic origin of symptoms in at least a proportion of these individuals. Patients with chest pain and normal coronary arteries have abnormal vasodilatory coronary blood flow responses and an increased sensitivity of the coronary microcirculation to vasoconstrictor stimuli (microvascular angina). Microvascular endothelial dysfunction appears to be responsible for these coronary microcirculation abnormalities. Given the high prevalence of peri- and post-menopausal women in cardiac syndrome X, it has been hypothesized that oestrogen deficiency may play a major role in the pathogenesis of this condition. Oestrogen vasoactive properties involve endothelium-dependent effects and, in postmenopausal women, forearm vasodilatation induced by acetylcholine is potentiated by the acute local administration of intravenous oestradiol. This suggests that endothelium-dependent responses in the peripheral circulation may be modulated by steroid hormones. Impairment of endothelial function in post-menopausal women with syndrome X has been reported by various groups and it could be hypothesized that oestrogen deficiency may contribute to the development of microvascular angina through endothelial dysfunction and that exogenous oestrogen administration may have a beneficial effect in syndrome X patients. This article reviews current knowledge regarding the role of oestrogen deficiency in the pathogenesis of syndrome X and the potential therapeutic role of oestrogen replacement therapy in women with chest pain and normal coronary arteriograms

Influence of exogenous estrogen administration on serum CA-125 originating from the endometrium

Objectives: The purpose of the study is to assess the endometrial contribution of serum CA-125 using exogenous estrogen administration by ruling out ovarian activity. A randomized, controlled, prospective study was designed to assess the endometrial contribution of serum CA-125 and its influence from estrogen administration in menopausal women. Methods: Twenty menopausal women with intact uterus and ovaries (study group) and 10 cases with previous total hysterectomy with intact ovaries (control group) were included in the study. The mean age of subjects in the study and control groups were similar at 53±1.9 (S.D.) and 51±2.7 years. The length of menopause in the study and control groups were also similar at 61.0±18 and 52.6±26.5 months, respectively. Group 1 consisted of 10 randomly selected cases and five controls who received 15 days of 50 μg/day transdermal 17β-estradiol (TE). Group 2 consisted of the next randomly selected 10 cases and five controls who had 15 days of transdermal 100 μg/day 17β-estradiol (Estraderm-Ciba) administration. Serum CA-125 and estradiol were measured at day 0, 15 by radioimmunoassay (RIA). Results: Serum mean CA-125 levels increased significantly in endometrium intact menopausal women from day 0 to 15 of TE administration in group 2 and 1, 70% and 6%, respectively ( P=0.03 and P=0.05, respectively). Interestingly, the increase in serum estradiol levels accompanied this change only in group 2. Conclusions: These results suggest that endometrial CA-125 secretion to serum is dependent on the dose of administered exogenous estrogen.

Use of exogenous estrogens in systemic lupus erythematosus

Objective: To review the current literature on the safety of using exogenous estrogens in patients with systemic lupus erythematosus (SLE). Method: A MEDLINE search for articles published between 1970 and 2000 regarding the relationship between estrogens and SLE was performed. Emphasis was put on human studies, treatment trials, and epidemiologic surveys. Results: The use of exogenous estrogens in healthy women increases the risk of SLE development. For patients with established SLE, a hypoestrogenemic state appears to be protective against severe flares, whereas exogenous estrogen administration or hyperestrogenemia induced by hormonal manipulation may exacerbate the disease in certain individuals. Both the use of oral contraceptives and the use of hormonal replacement therapy (HRT) increase the chance of venous thromboembolism. The presence of antiphospholipid antibodies may aggravate the risk of thrombosis in SLE. In retrospective studies, HRT appears to be well tolerated in postmenopausal SLE patients. Conclusions: There are no prospective data that show a deleterious effect of exogenous estrogens on disease activity in human SLE. Oral contraceptives may be considered for patients with SLE in the absence of active nephritis or antiphospholipid antibodies. The slight increase in venous thromboembolic risk should not be the chief deterrent to the use of HRT in postmenopausal SLE patients, considering its various health benefits. Semin Arthritis Rheum 30:426-435. Copyright © 2001 by W.B. Saunders Company

Increase of leptin levels following exogenous administration of estrogen in women with normal menstruation.

To investigate the acute effect of exogenous estrogen on the changes of leptin production, the time sequence of changes in plasma leptin concentration were determined following i.v. administration of premarin, a conjugated estrogen, during the follicular phase (days 5-9) in women (n = 12) with normal menstruation. The mean circulating estradiol level abruptly (P < 0.0001) increased from 4 h to a level of 72-fold from baseline and was still significantly (P < 0.05) elevated at 72 h after injection of conjugated estrogen. The mean leptin level showed a significant (P < 0.05) gradual increase from 24 h (10.8 +/- 1.0 ng/mL) continuing on up to a peak at 32 h (11.6 +/- 0.9 ng/mL); significantly (P < 0.05) sustained to 48 h (10.7 +/- 0.7 ng/mL) and then slowly decreased at 56 h after injection of premarin, as compared with the preinjection level (7.8 +/- 0.7 ng/mL). However, there were no changes of leptin levels in women (n = 10) who received normal saline injection. These data clearly suggest that a higher level of estrogen could stimulate the increase of plasma leptin concentration during the follicular phase of normal cyclic women. This result provides evidence that supraphysiological level of estrogen may act on the adipocyte to modulate leptin production through the endocrine mechanism.

Safety of Hormonal Replacement Therapy in Postmenopausal Patients with Systemic Lupus Erythematosus

It remains controversial whether administration of exogenous estrogens is safe in systemic lupus erythematosus (SLE). The current study was undertaken to determine the effect of hormone replacement therapy (HRT) on the rate and magnitude of flares in a cohort of postmenopausal SLE patients. Thirty-four patients were prospectively followed. The frequency and severity of disease exacerbations in 11 patients who received HRT was compared with 23 patients who did not receive HRT. Our results showed that both users and non-users of HRT had a comparable age of disease onset, duration of disease, clinical manifestations, and duration of follow-up. No significant increase in the rate (0.12 relapses/patient-year in HRT group vs 0.16 relapses/patient-year in the non-HRT group, p=0.90) or magnitude (total SLEDAI score increase during flares/patient-year in the HRT and non-HRT groups were 0.55 and 1.22, respectively, p=0.57) of flares could be demonstrated in patients who received HRT over a median follow-up period of 35 months. We concluded that HRT appeared to be well tolerated and safe in postmenopausal SLE patients. Its potential beneficial effect may outweigh its deleterious effect on disease activity.

R-233. Discrepancy in the correlation between circulating oestrone sulphate and oestradiol concentrations during ovarian hyperstimulation and exogenous oestrogen administration in women

R-233. Discrepancy in the correlation between circulating oestrone sulphate and oestradiol concentrations during ovarian hyperstimulation and exogenous oestrogen administration in women

Endogenous estrogen and acetylcholine-induced vasodilation in normotensive women.

Acute exogenous estrogen administration enhances endothelial function in postmenopausal women. To evaluate the effect of endogenous estrogen on endothelium-dependent vasodilation, in 10 fertile normotensive women (age range 45 to 51 years) we studied the changes in forearm blood flow (strain-gauge plethysmography) induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, 1.5 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, or sodium nitroprusside (1, 2, 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator, in basal conditions and within 1 month after ovariectomy. As control subjects, 10 matched healthy women were also evaluated. In basal condition, vasodilation to acetylcholine and sodium nitroprusside was similar in patients and control subjects. Ovariectomy was followed by endogenous estrogen deprivation (from 71.6 +/- 31.3 to < 12 pg/mL) and was associated with a significant (P < .01) reduction in acetylcholine-induced vasodilation compared with baseline (maximum percent increase in forearm blood flow: baseline 568.2 +/- 47.1%; ovariectomy 309.5 +/- 37.4%); the response to sodium nitroprusside was unaffected by ovariectomy (maximum percent increase in forearm blood flow: baseline 526.4 +/- 36.5%; ovariectomy 454.7 +/- 47.2%; P = NS). In 6 of 10 patients, the study was repeated after 3 months of estrogen replacement therapy (17 beta-estradiol, 50 micrograms/d by transdermal patches). Exogenous estrogen restored acetylcholine-induced vasodilation (maximum percent increase in forearm blood flow: 548.9 +/- 43.1%; P < .01 versus ovariectomy), which was no longer different from baseline, whereas the response to sodium nitroprusside was not affected (maximum percent increase in forearm blood flow: 480.2 +/- 39.3%; P = NS). These results suggest a protective role of endogenous estrogen on endothelium-dependent vasodilation in the forearm vascular bed of normotensive women.

Short-term gonadotropin suppression with oral contraceptives benefits poor responders prior to controlled ovarian hyperstimulation.

A comparative study of four treatment regimens for women with a history of poor response to controlled ovarian hyperstimulation (COH) during attempts at in vitro fertilization (IVF) and embryo transfer suggested the feasibility of pretreatment with oral contraceptives (OCs). The 60 women enrolled in the study exhibited one or more of the following in an initial stimulated IVF cycle: three or fewer dominant follicles recruited serum estradiol levels of 300 pg/ml or below and/or a spontaneous luteinizing hormone (LH) surge prior to oocyte retrieval. Study subjects were assigned to one of four protocols: Group I--OCs for 3 weeks followed by COH; Group II--luteal phase leuprolide acetate with subsequent COH; Group III--short-flare Lupron with subsequent COH; and Group IV--COH alone. COH consisted of 150 IU/day of pure follicle-stimulating hormone (pFSH) and 150 IU/day of human menopausal gonadotropin (hMG). The mean age of women in each group ranged from 36.0 to 38.8 years. There were no significant differences among groups in terms of number of days of stimulation total ampoules of hMG and pFSH required peak serum estradiol and progesterone number of oocytes retrieved and fertilized and embryos transferred. However the pregnancy rate was significantly higher (p < 0.05) in Group I (9/30 30%) than in Group II (2/32 6%) Group III (0/11 0%) and Group IV (0/10 0%). The good outcome associated with OC pretreatment may reflect production or alterations of local ovarian growth factors and/or changes in endometrial expression. Administration of exogenous estrogen may be particularly beneficial for perimenopausal women in their forties with ovarian follicular depletion.

Estrogen Inhibits Sphincter of Oddi Motility

Gallstones and sphincter of Oddi dysfunction are both more common in women than men, suggesting that endogenous hormones may play an important role in these conditions. Female sex hormones are known to affect cholesterol metabolism and gallbladder motility. However, the effect of these hormones on the sphincter of Oddi has not previously been studied. We therefore tested the hypothesis that exogenous estrogen administration would inhibit sphincter of Oddi motility. Twenty-three male prairie dogs fed a nonlithogenic diet were studied. Under α-chloralose anesthesia, a side hole pressure-monitored perfusion catheter was positioned in the sphincter of Oddi and perfused with degassed water at 0.15 ml/min. Femoral arterial and venous catheters were placed. Sphincter of Oddi phasic wave frequency (F), amplitude (A), and motility index (MI = F × A), as well as arterial blood pressure (BP), were monitored for 10-min intervals before (control), during 20-min intravenous infusions of 0.1, 1, or 10 μg/kg β-estradiol, and for 20 min after estradiol infusion. No response was observed at the 0.1- or 1-μg doses. Sphincter of Oddi motility was significantly (P < 0.05) reduced during estrogen infusion at the higher dose of 10 μg, primarily due to decreased phasic wave frequency. Sphincter motility remained depressed for at least 20 min following estrogen infusion. We conclude that estrogen effects on the sphincter of Oddi may contribute to the higher incidence of gallstones and sphincter dysfunction seen in premenopausal women.

Vaginal Flora in Postmenopausal Women: The Effect of Estrogen Replacement

Objective:To determine the effect of estrogen replacement therapy (ERT) on the vaginal flora of postmenopausal women. Methods: Vaginal cultures were obtained from 15 postmenopausal women whose hormonal statuses were documented by serum follicle-stimulating hormone (FSH) and serum estrogen levels. After 8 weeks of ERT, consisting of 0.1 mg of estradiol delivered daily by dermal patch, the vaginal cultures were repeated, as were measurements of the vaginal pH, serum FSH, and serum estrogen levels. Results: Vaginal cultures revealed no significant change in the incidence of lactobacilli or of all aerobes. However, the incidence of anaerobic species fell after treatment from 47% to 13% (P = 0.05), and the incidence of anaerobic gram-negative rods declined after treatment from 40% prior to ERT to 7% (P = 0.035). Prior to ERT, the difference in mean vaginal pH between lactobacilli-positive and lactobacilli-negative subjects was not significant, but, following the administration of exogenous estrogen, the lactobacilli-positive subjects exhibited a significantly lower mean vaginal pH (4.4 ± 0.4) relative to the lactobacilli-negative population (5.2 ± 0.3) (P = 0.02). Conclusions: We conclude that women on ERT are less likely to have vaginal colonization with anaerobic bacteria when compared with women not using replacement therapy. Estrogen replacement may potentiate the effect of lactobacilli on vaginal pH.