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1.
BMC Prim Care ; 25(1): 241, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38970006

ABSTRACT

BACKGROUND: The Collaborative Care Model (CoCM) increases access to mental health treatment and improves outcomes among patients with mild to moderate psychopathology; however, it is unclear how effective CoCM is for patients with elevated suicide risk. METHODS: We examined data from the Penn Integrated Care program, a CoCM program including an intake and referral management center plus traditional CoCM services implemented in primary care clinics within a large, diverse academic medical system. In this community setting, we examined: (1) characteristics of patients with and without suicidal ideation who initiated CoCM, (2) changes in suicidal ideation (Patient Health Questionnaire-9 [PHQ-9] item 9), depression (PHQ-9 total scores), and anxiety (Generalized Anxiety Disorder Scale-7 scores) from the first to last CoCM visit overall and across demographic subgroups, and (3) the relationship between amount of CoCM services provided and degree of symptom reduction. RESULTS: From 2018 to 2022, 3,487 patients were referred to CoCM, initiated treatment for at least 15 days, and had completed symptom measures at the first and last visit. Patients were 74% female, 45% Black/African American, and 45% White. The percentage of patients reporting suicidal ideation declined 11%-7% from the first to last visit. Suicidal ideation severity typically improved, and very rarely worsened, during CoCM. Depression and anxiety declined significantly among patients with and without suicidal ideation and across demographic subgroups; however, the magnitude of these declines differed across race, ethnicity, and age. Patients with suicidal ideation at the start of CoCM had higher depression scores than patients without suicidal ideation at the start and end of treatment. Longer CoCM episodes were associated with greater reductions in depression severity. CONCLUSIONS: Suicidal ideation, depression, and anxiety declined following CoCM among individuals with suicidal ideation in a community setting. Findings are consistent with emerging evidence from clinical trials suggesting CoCM's potential for increasing access to mental healthcare and improving outcomes among patients at risk for suicide.


Subject(s)
Anxiety , Depression , Suicidal Ideation , Humans , Female , Male , Middle Aged , Adult , Depression/epidemiology , Depression/therapy , Depression/psychology , Anxiety/epidemiology , Anxiety/therapy , Anxiety/psychology , Primary Health Care , Young Adult , Delivery of Health Care, Integrated
2.
Suicide Life Threat Behav ; 54(1): 15-23, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37916734

ABSTRACT

INTRODUCTION: The Collaborative Care Model (CoCM) is an evidence-based approach which embeds behavioral health providers (BHPs) into primary care. Whether patients with suicidal ideation (SI) are willing to engage in CoCM is unclear. METHODS: Using Patient Health Questionnaire-9 (PHQ-9) administrative data from primary care practices within an urban academic health system, we identified patients with and without SI who were referred to a CoCM BHP. We compared engagement, defined as attendance at ≥1 CoCM visit, across groups. RESULTS: Between 2018 and 2022, 7391 primary care patients were referred to a CoCM BHP. Eight hundred and ninety-two of these patients reported SI on the PHQ-9 (754 on "several days" during the previous 2 weeks and 138 on "more than half or most days"). Across groups, most patients engaged in CoCM. Patients reporting SI on several days engaged at a lower rate (61.4%) than those reporting SI on more than half or most days (65.9%). Both SI groups engaged at a lower rate than the 6499 patients who did not report SI (67.5%). CONCLUSION: Most patients referred to a CoCM BHP engaged in ≥1 visit. Rates were lower for patients with SI, with the lowest rate among those reporting SI on several days.


Subject(s)
Psychiatry , Suicidal Ideation , Humans , Follow-Up Studies , Primary Health Care
3.
Prev Med ; 172: 107538, 2023 07.
Article in English | MEDLINE | ID: mdl-37156430

ABSTRACT

Financial incentives are a controversial strategy for increasing vaccination. In this systematic review, we evaluated: 1) the effects of incentives on COVID-19 vaccinations; 2) whether effects differed based on study outcome, study design, incentive type and timing, or sample sociodemographic characteristics; and 3) the cost of incentives per additional vaccine administered. We searched PubMed, EMBASE, Scopus, and Econlit up to March 2022 for terms related to COVID, vaccines, and financial incentives, and identified 38 peer-reviewed, quantitative studies. Independent raters extracted study data and evaluated study quality. Studies examined the impact of financial incentives on COVID-19 vaccine uptake (k = 18), related psychological outcomes (e.g., vaccine intentions, k = 19), or both types of outcomes. For studies of vaccine uptake, none found that financial incentives had a negative effect on uptake, and most rigorous studies found that incentives had a positive effect on uptake. By contrast, studies of vaccine intentions were inconclusive. While three studies concluded that incentives may negatively impact vaccine intentions for some individuals, they had methodological limitations. Study outcomes (uptake versus intentions) and study design (experimental versus observational frameworks) appeared to influence results more than incentive type or timing. Additionally, income and political affiliation may moderate responses to incentives. Most studies evaluating cost per additional vaccine administered found that they ranged from $49-75. Overall, fears about financial incentives decreasing COVID-19 vaccine uptake are not supported by the evidence. Financial incentives likely increase COVID-19 vaccine uptake. While these increases appear to be small, they may be meaningful across populations. Registration: PROSPERO, CRD42022316086 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022316086).


Subject(s)
COVID-19 , Motivation , Humans , COVID-19 Vaccines , COVID-19/prevention & control , Vaccination , Research Design
4.
J Occup Environ Med ; 65(7): e478-e484, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37043399

ABSTRACT

OBJECTIVE: Faculty at academic medical institutions are at increased risk for burnout. This study aimed to assess faculty perceptions of wellness needs and identify strategies to optimize engagement with individualized wellness resources. METHODS: Semistructured interviews were conducted with 37 faculty members in one US academic medical center. RESULTS: Participants identified significant barriers to achieving emotional health and wellness goals. Areas where participants identified needing the most support included interpersonal relationships, accountability for wellness goals, career support, financial resources, and mentorship. Most participants were unaware of all wellness resources available at their institution. Participants recommended regular marketing and emphasizing confidentiality of employer-sponsored programs. They also provided feedback on specific dissemination and marketing methods. CONCLUSIONS: This research underscores the need for wellness resources for faculty and the importance of intentional dissemination of these resources to optimize uptake.


Subject(s)
Burnout, Professional , Faculty, Medical , Humans , Faculty, Medical/psychology , Interpersonal Relations , Burnout, Professional/psychology , Academic Medical Centers , Burnout, Psychological
5.
Pilot Feasibility Stud ; 8(1): 181, 2022 Aug 13.
Article in English | MEDLINE | ID: mdl-35964151

ABSTRACT

BACKGROUND: Primary care is an ideal setting to connect individuals at risk for suicide to follow-up care; however, only half of the patients referred from the primary care attend an initial mental health visit. We aim to develop acceptable, feasible, low-cost, and effective new strategies to increase treatment initiation among at-risk individuals identified in primary care. METHODS: We will conduct a multi-phase, mixed-methods study. First, we will conduct a chart review study by using administrative data, including medical records, to identify characteristics of primary care patients at risk for suicide who do or do not attend an initial mental health visit following a referral. Second, we will conduct a mixed methods study by using direct observations and qualitative interviews with key stakeholders (N = 65) to understand barriers and facilitators to mental health service initiation among at-risk individuals. Stakeholders will include patients with suicidal ideation referred from primary care who do and do not attend a first mental health visit, primary care and behavioral health providers, and individuals involved in the referral process. We also will collect preliminary self-report and behavioral data regarding potential mechanisms of behavior change (i.e., self-regulation and social support) from patients. Third, we will leverage these findings, relevant frameworks, and the extant literature to conduct a multi-arm, non-randomized feasibility trial. During this trial, we will rapidly prototype and test strategies to support attendance at initial mental health visits. Strategies will be developed with subject matter experts (N = 10) and iteratively pilot tested (~5 patients per strategy) and refined. Research will be completed in the Penn Integrated Care Program (PIC), which includes fourteen primary care clinics in Philadelphia that provide infrastructure for electronic referrals, patient communication, and data access. DISCUSSION: We will leverage frameworks and methods from behavioral economics and implementation science to develop strategies to increase mental health treatment initiation among individuals at risk for suicide identified in primary care. This project will lead to an evaluation of these strategies in a fully powered randomized trial and contribute to improvements in access to and engagement in mental health services for individuals at risk for suicide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05021224.

6.
J Minim Access Surg ; 15(1): 56-62, 2019.
Article in English | MEDLINE | ID: mdl-29483381

ABSTRACT

BACKGROUND: Bedside diagnostic laparoscopy could be helpful in extremely critically ill patients. The aim of this retrospective study is to evaluate the safety and diagnostic accuracy of bedside diagnostic laparoscopy in the identification of intra-abdominal pathology in critically ill patients and to compare its accuracy and outcomes with the ones of laparotomy. PATIENTS AND METHODS: A retrospective review was conducted on the medical records of patients admitted to the Intensive Care Unit (ICU) of Careggi University Hospital and submitted to bedside diagnostic laparoscopy between January 2006 and May 2017. This group of patients was compared with a group of patients that were admitted to the ICU and submitted directly to explorative laparotomy for suspected intra-abdominal pathologies. RESULTS: One hundred and twenty-nine patients (M/F = 81/48, mean age = 71.64 years) underwent bedside diagnostic laparoscopy in ICU. 154 patients instead were submitted directly to explorative laparotomy in operatory room (mean age 75.70 years, M/F = 94/60). Among the 129 patients submitted to bedside laparoscopy, 53.49% were positive for intra-abdominal pathologies whereas 46.51% were negative, while among the 154 patients submitted directly to laparotomy, 76.62% were positive for intra-abdominal pathologies whereas 23.38% were negative. In 55.03% of all patients submitted to bedside laparoscopy, a non-therapeutic laparotomy was avoided, while the 33.76% of patients submitted directly to laparotomy had a non-therapeutic laparotomy that could be avoidable. CONCLUSIONS: Our results pinpoint the advantages of performing bedside diagnostic laparoscopy in the ICU setting, which can be considered an option every time there is the suspicion of an intra-abdominal pathology.

7.
Menopause ; 14(1): 63-73, 2007.
Article in English | MEDLINE | ID: mdl-17075429

ABSTRACT

OBJECTIVE: Drospirenone is the unique progestin derived from 17-spironolactone used for contraception and hormone therapy. Few data are available concerning the effects of drospirenone on the central nervous system and neuroendocrine milieu. The opioid beta-endorphin and the neurosteroid allopregnanolone are considered markers of neuroendocrine functions, and their synthesis and activity are regulated by gonadal steroids. The aim of the present study was to evaluate the effect of a 2-week oral treatment with drospirenone, estradiol valerate, and combined therapy of drospirenone + estradiol valerate on central and peripheral beta-endorphin and allopregnanolone levels in ovariectomized female rats. DESIGN: Seven groups of Wistar ovariectomized rats received oral drospirenone (0.1, 0.5, and 1.0 mg/kg per day), estradiol valerate (0.05 mg/kg per day), or drospirenone (0.1, 0.5, and 1.0 mg/kg per day) + estradiol valerate (0.05 mg/kg per day). One group of fertile and one group of ovariectomized rats were used as controls. beta-endorphin levels were measured in frontal and parietal lobes, hippocampus, hypothalamus, anterior and neurointermediate pituitary, and plasma, and allopregnanolone content was assessed in frontal and parietal lobes, hippocampus, hypothalamus, anterior pituitary, adrenal glands, and serum. RESULTS: Ovariectomy induced a significant decrease in beta-endorphin and allopregnanolone content in all brain areas analyzed and in circulating levels, whereas it increased allopregnanolone content in the adrenal gland. Estradiol valerate replacement increased beta-endorphin and allopregnanolone levels in all brain areas analyzed and in plasma/serum. Drospirenone treatment significantly increased beta-endorphin levels in all brain areas analyzed (with the only exception being the parietal lobe), whereas it produced no effect on allopregnanolone levels. The addition of drospirenone to estradiol valerate did not modify the effects of estradiol valerate on beta-endorphin or allopregnanolone levels. Drospirenone showed an additive and synergistic effect with estradiol in the neurointermediate lobe on beta-endorphin synthesis. CONCLUSIONS: Drospirenone significantly increases central and circulating beta-endorphin levels and does not seem to interfere with allopregnanolone production.


Subject(s)
Androstenes/pharmacology , Central Nervous System/drug effects , Estradiol/analogs & derivatives , Mineralocorticoid Receptor Antagonists/pharmacology , Pregnanolone/metabolism , beta-Endorphin/metabolism , Administration, Oral , Animals , Central Nervous System/metabolism , Dose-Response Relationship, Drug , Drug Combinations , Estradiol/pharmacology , Female , Ovariectomy , Pregnanolone/blood , Rats , Rats, Wistar , beta-Endorphin/blood
8.
Gynecol Endocrinol ; 22(11): 627-35, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17145649

ABSTRACT

OBJECTIVE: The aging process is associated with a decline in the circulating Delta5-androgen dehydroepiandrosterone (DHEA) and its sulfate ester, dehydroepiandrosterone sulfate (DHEAS). The present study aimed to evaluate the effects of a long-term (12 months) oral DHEA administration (25 mg/day) on adrenal function, before and after 3, 6 and 12 months of treatment. METHOD: Postmenopausal women belonging to two age groups, 50-55 years (n = 10) and 60-65 years (n = 10), were studied. Adrenal function was assessed in basal conditions, after suppression with dexamethasone (DXM) and following a stimulation test with adrenocorticotropic hormone (ACTH) (10 microg bolus). Serum levels of DHEA, DHEAS, androstenedione (Delta4-A), allopregnanolone, 17-hydroxyprogesterone (17-OHP) and cortisol were measured and the effects of DHEA supplementation on specific adrenal enzymatic pathways were evaluated by calculating precursor/product ratios (17-OHP/cortisol, 17-OHP/Delta4-A, DHEA/Delta4-A and DHEA/DHEAS). RESULTS: DHEA supplementation annulled the age-related differences in DHEA and DHEAS levels and induced a marked increase in all steroids, except for cortisol, after 3-6 months of treatment. Serum cortisol levels decreased from the 3rd month, both in younger and older subjects. DHEA supplementation did not affect DXM-induced suppression of adrenal steroidogenesis. During the treatment period all adrenal androgens and progestins showed a significant increase in their response to ACTH, while the cortisol response decreased significantly. The results suggest a significant DHEA-induced change in adrenal enzymatic activities, as also evidenced by the change in precursor/product ratios during therapy. CONCLUSION: Chronic DHEA administration is capable of modifying circulating levels of androgens and progestins in both early and late postmenopausal women by modulating the age-related changes in adrenal function.


Subject(s)
Adjuvants, Immunologic/administration & dosage , Adrenal Glands/drug effects , Adrenocorticotropic Hormone/pharmacology , Dehydroepiandrosterone/administration & dosage , Dehydroepiandrosterone/pharmacology , Postmenopause/drug effects , Administration, Oral , Adrenal Glands/enzymology , Aged , Dexamethasone/pharmacology , Drug Interactions , Female , Humans , Middle Aged , Steroids/blood , Time Factors
9.
Neuroendocrinology ; 83(5-6): 348-59, 2006.
Article in English | MEDLINE | ID: mdl-16931878

ABSTRACT

The increased use of hormonal therapies has led to the study of the properties of different progestin molecules and their effects on the central nervous system. The central and peripheral levels of neurosteroid allopregnanolone and the opioid peptide beta-endorphin (beta-END) are regulated by estrogens. The aim of the present study was to investigate the effects of a 2-week oral treatment with micronized progesterone or medroxyprogesterone acetate (MPA) alone or in addition to estradiol valerate (E2V) on central and peripheral allopregnanolone and beta-END levels in ovariectomized (OVX) female rats. Thirteen groups of Wistar OVX rats received one of the following treatments: oral progesterone (2, 4 or 8 mg/kg/day); oral MPA (0.05, 0.1 or 0.2 mg/kg/day); E2V (0.05 mg/kg/day); E2V + progesterone (0.05 mg/kg/day + 2, 4 or 8 mg/kg/day), or E2V + MPA (0.05 mg/kg/day + 0.05, 0.1 or 0.2 mg/kg/day) for 14 days. One group of fertile and one group of OVX rats were used as controls. The concentration of allopregnanolone was assessed in the frontal and parietal lobes, hypothalamus, hippocampus, anterior pituitary, adrenals and serum, while the beta-END content was assessed in the frontal and parietal lobes, hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma. E2V administration reverted the ovariectomy-induced reduction in allopregnanolone and beta-END. Progesterone and MPA increased allopregnanolone levels in all tissues except in the adrenal gland. The combined administration of progesterone or MPA and E2V determined a further increase in allopregnanolone levels with respect to E2V alone except in the adrenal gland and hippocampus only after MPA treatment. Progesterone did not affect beta-END levels in the frontal and parietal lobes, hippocampus and anterior pituitary, while it caused an increase plasma, hypothalamic and neurointermediate pituitary beta-END levels. MPA only affected beta-END levels in the hippocampus and in the neurointermediate lobe. The combined administration of progesterone or MPA and E2V did not alter the effect of estradiol or it determined a further dose-dependent increase in beta-END levels. In conclusion, this study demonstrates that progesterone and MPA have a similar but not identical effect on central and peripheral allopregnanolone and beta-END levels. Their association with an estrogenic compound does not interfere with the positive effects produced by estrogen on allopregnanolone and beta-END brain content.


Subject(s)
Estradiol/analogs & derivatives , Medroxyprogesterone Acetate/administration & dosage , Pregnanolone/metabolism , Progesterone/administration & dosage , beta-Endorphin/metabolism , Administration, Oral , Adrenal Glands/drug effects , Adrenal Glands/metabolism , Animals , Brain/drug effects , Brain/metabolism , Dose-Response Relationship, Drug , Drug Therapy, Combination , Estradiol/administration & dosage , Estrogens, Conjugated (USP)/administration & dosage , Female , Hormone Replacement Therapy , Hormones/administration & dosage , Models, Animal , Neurosecretory Systems/drug effects , Ovariectomy , Pregnanolone/blood , Progesterone/physiology , Rats , Rats, Wistar , beta-Endorphin/blood
10.
Fertil Steril ; 80(6): 1495-501, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14667889

ABSTRACT

OBJECTIVE: To evaluate the effects of a low-dose DHEA supplementation on hormonal parameters in early and late postmenopausal women. DESIGN: Prospective case study. SETTING: Postmenopausal women in a clinical research environment. PATIENT(S): Twenty postmenopausal women were divided in two groups according to age (50-55 and 60-65 years). INTERVENTION(S): All patients underwent hormonal evaluation before and at 3, 6, 9, and 12 months of therapy (25 mg/d of DHEA orally). Pelvic ultrasound examination and Kupperman score were performed before and after 3, 6, and 12 months of therapy. MAIN OUTCOME MEASURE(S): Plasma DHEA, DHEAS, estrone (E1), E2, P, androstenedione (A), T, dihydrotestosterone, 17alpha-hydroxyprogesterone (17-OHP), cortisol (F), allopregnanolone, beta-endorphin, sexual hormone-binding globulin (SHBG), LH, FSH, growth hormone (GH), and insulin-like growth factor-1 (IGF-1) concentrations. RESULT(S): The levels of all the steroids that derive from DHEA metabolism increased in plasma with DHEA administration. Also neurosteroids (namely allopregnanolone) and endorphin showed increased plasma levels, whereas both gonadotropins were significantly reduced. Endometrial thickness did not change throughout the study period. CONCLUSION(S): Administration of low doses (25 mg) of DHEA positively modulates several endocrine parameters in early and late postmenopausal women, inducing the increase of the androgenic, estrogenic, and progestogenic milieu and reducing the climateric symptoms, similarly to estroprogestin replacement therapy. These data suggest that DHEA supplementation is a more effective replacement therapy than a simple "dietary supplement."


Subject(s)
Androgens/blood , Dehydroepiandrosterone/therapeutic use , Dietary Supplements , Estrogens/blood , Postmenopause/physiology , Age Factors , Aged , Dehydroepiandrosterone/administration & dosage , Dehydroepiandrosterone/blood , Dehydroepiandrosterone Sulfate/blood , Female , Follicle Stimulating Hormone/blood , Follow-Up Studies , Human Growth Hormone/blood , Humans , Luteinizing Hormone/blood , Middle Aged , Postmenopause/blood , Postmenopause/drug effects , Sex Hormone-Binding Globulin/analysis , Time Factors
11.
Maturitas ; 43(3): 195-206, 2002 Nov 20.
Article in English | MEDLINE | ID: mdl-12443836

ABSTRACT

OBJECTIVES: Several natural or synthetic estrogenic molecules are commonly used in oral hormone replacement therapy for the relief of menopausal complaints and for the primary prevention of cardiovascular disease and osteoporosis. Little information is available concerning the comparative efficacy of different compounds on neuroendocrine function. The opioid peptide beta-endorphin (beta-EP), and the neurosteroid allopregnanolone are considered markers of neuroendocrine function and their synthesis and action is regulated by gonadal steroids. The present study aimed to investigate the effects of a 2-week oral treatment with estradiol valerate (EV), estrone sulphate (ES), or conjugated equine estrogen (CEE) on central and peripheral beta-EP and allopregnanolone levels in ovariectomized (OVX) female rats. METHODS: Twelve groups of Wistar OVX rats received oral EV (0.05, 0.1, 0.5 and 1 mg/Kg/day) or ES (0.1, 0.5, 1 and 2 mg/Kg/day), or CEE (0.1, 0.5, 1 and 2 mg/Kg/day) for 14 days. One group of fertile and one group of OVX rats were used as controls. beta-EP content was assessed in hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma, while allopregnanolone content was assessed in hypothalamus, hippocampus, anterior pituitary, adrenals and serum. RESULTS: Ovariectomy induced a significant decrease in beta-EP and allopregnanolone content in hypothalamus, hippocampus, pituitary, and serum, while it increased allopregnanolone content in the adrenals. In OVX rats, the administration of each molecule reversed the ovariectomy-induced beta-EP and allopregnanolone changes in a dose-dependent fashion, therefore completely restoring their concentration. At higher doses, the estrogenic compounds induced significantly higher levels of allopregnanolone and beta-EP than in fertile rats. CEE induced higher allopregnanolone levels in hypothalamus, anterior pituitary and serum than the other estrogenic molecules, and in the hippocampus with respect to EV alone. CEE produced higher beta-EP levels in the hippocampus and hypothalamus with respect to EV and ES. CONCLUSION: In the examined tissue and serum estrogens restore the ovariectomy induced changes in allopregnanolone and beta-EP content in a dose-dependent manner; the magnitude of these effects is not uniform and it is related to the different tissues and the employed compounds.


Subject(s)
Estradiol/analogs & derivatives , Estradiol/pharmacology , Estrogens, Conjugated (USP)/pharmacology , Estrone/analogs & derivatives , Estrone/pharmacology , Pregnanolone/metabolism , beta-Endorphin/drug effects , Administration, Oral , Animals , Dose-Response Relationship, Drug , Estradiol/administration & dosage , Estrogen Replacement Therapy , Estrogens, Conjugated (USP)/administration & dosage , Estrone/administration & dosage , Female , Hippocampus/drug effects , Hypothalamus/drug effects , Ovariectomy , Pituitary Gland/drug effects , Pregnanolone/blood , Rats , Rats, Wistar , Uterus/drug effects , beta-Endorphin/blood , beta-Endorphin/metabolism
12.
Fertil Steril ; 77(5): 1018-27, 2002 May.
Article in English | MEDLINE | ID: mdl-12009361

ABSTRACT

OBJECTIVE: To investigate the effects of oral estradiol valerate (EV); EM-652, a new-generation selective estrogen receptor modulator; and both agents on central and peripheral beta-endorphin (beta-EP) and allopregnanolone levels in fertile and ovariectomized rats. DESIGN: Prospective study. SETTING: Animal laboratory in an academic research environment. ANIMALS: Thirteen groups of eight Wistar female rats received oral EV (0.01 or 0.05 mg/kg of body weight daily), EM-652 (0.1, 1, or 5 mg/kg daily), or EV (0.05 mg/kg daily) and EM-652 (0.1, 1, or 5 mg/kg/daily) for 14 days. INTERVENTION(S): beta-Endorphin levels content in the hypothalamus, hippocampus, anterior and neurointermediate pituitary, and plasma were measured. Allopregnanolone levels in the hypothalamus, hippocampus, anterior pituitary, adrenal glands, and serum were measured. MAIN OUTCOME MEASURE(S): beta-Endorphin and allopregnanolone levels. RESULT(S): In ovariectomized rats, administration of EV or EM-652 reverses changes in beta-EP and allopregnanolone levels induced by ovariectomy. Administration of EM-652 plus EV prevents the increase in beta-EP and allopregnanolone levels induced by EV in the hippocampus, hypothalamus, and pituitary but not in the adrenal glands and serum. CONCLUSIONS: In ovariectomized rats, EM-652 has an estrogen-like action that becomes antiestrogenic in the presence of EV administration. In fertile animals, EM-652 exerts estrogen-like or slight antiestrogenic effects.


Subject(s)
Adrenal Glands/metabolism , Brain/metabolism , Estradiol/analogs & derivatives , Estradiol/administration & dosage , Piperidines/pharmacology , Pregnanolone/blood , Selective Estrogen Receptor Modulators/pharmacology , beta-Endorphin/metabolism , Administration, Oral , Animals , Drug Synergism , Female , Fertility/physiology , Hippocampus/metabolism , Hypothalamus/metabolism , Ovariectomy , Pituitary Gland/metabolism , Rats , Rats, Wistar , beta-Endorphin/blood
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