High levels of intrauterine corticotrophin-releasing hormone, urocortin, tryptase, and interleukin-8 in spontaneous abortions.
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Abortion, Spontaneous↗
Biomedical subjects
F Petraglia
Publications and source records attributed to F Petraglia.
Maternal serum inhibin A levels are a marker of a viable trophoblast in incomplete and complete miscarriage.
OBJECTIVE: From early gestation the human trophoblast secretes large amounts of inhibin A and activin A, and their measurement provides a value for predicting the outcome in women who become pregnant after assisted reproductive techniques. The aim of the study was to investigate the putative role of maternal serum inhibin A and activin A levels as markers of a viable trophoblast in women who miscarry. DESIGN: Controlled cross-sectional study. METHODS: One group consisted of 65 healthy pregnant women (controls), progressing to deliver a healthy singleton baby and another group consisted of 54 miscarriages (38 incomplete (27 non-viable, 11 anembryonic pregnancies) and 16 complete). Maternal blood samples were collected between 5 and 12 weeks of gestation. RESULTS: Serum human chorionic gonadotrophin concentrations in women with incomplete or complete miscarriages were significantly (both P<0.001) lower than in controls; activin A levels being lowest only in women with a complete miscarriage (P<0.001). On the other hand, inhibin A levels were significantly lower in incomplete or complete miscarriage than in controls (both P<0.0001). CONCLUSIONS: Maternal serum inhibin A, but not activin A, determination reflects the lack of a viable trophoblast in complete miscarriage.
Abortion, Spontaneous↗
Management of sexual dysfunctions in women.
The deeper understanding of female physiology changed the perspective used to evaluate sexual difficulties. Systems like: vascular, neurological, biochemical, and endocrine are investigated as their modifications for aging or medical conditions may alter the sexual responsivity of women. New data imply that pharmacological interventions may become suitable for women. Gonadal steroids influence mood, wellbeing, and genital physiology but evidence of actions is controversial. Hormone imbalance provokes symptoms that may also derive from other conditions. Clinicians must exclude dismetabolism, depression and family crisis before diagnosing gonadal problems. The female androgen insufficiency syndrome was defined in July 2001 as altered mood, memory and wellbeing, and loss of desire. Estrogen maintains wellbeing and healthy genitals, influencing mood and sexuality. Progesterone provokes tension and nervousness, causing premenstrual syndrome. Hormone replacement is indicated in the treatment of endocrine deficiency. In research projects women receiving one preparation containing androgen reported improvement of mood, and arousal. Sildenafil cures approximately 25% of sexually dysfunctional, menopausal patients; being more effective with hormone replacement therapy (HRT) and consistently active against the block of antidepressants on orgasm. Added to psychiatric regimens, sildenafil ameliorates excitement. Sex therapy helps patients change behavior, overcome anger, communicate needs and redefine sex. We strongly believe that such crucial aspects must be addressed in therapy, even when the etiology is organic.
Androgens↗
Combination of statins and hormone replacement therapy in postmenopausal women is associated with increased bone mineral density.
Recent studies have shown that statins might be potent inhibitors of bone resorption and osteoclast number, and there is evidence for their bone anabolic effects. Statin treatment seems to protect against non-pathological fractures in older women. However, contradictory findings have been obtained. In this retrospective study we found that postmenopausal women on statins and hormone replacement therapy (HRT) showed higher bone mineral density than women on HRT alone. This evidence provides further confirmation of the effect of statins on bone turnover and shows that the combination of HRT and statins reduces the risk of bone fracture by virtue of the antiresorptive effect of HRT and the anabolic and antiresorptive effects of statins.
Absorptiometry, Photon↗
Assessment of the QoL in Italian menopausal women: comparison between HRT users and non-users.
OBJECTIVES: The aim of this cross-sectional study was to describe QoL in a large sample of women attending menopause centres and compare untreated postmenopausal women and matched HRT users by employing the Women's Health Questionnaire (WHQ) and two generic instruments, the SF-36 and the EQ-5D. METHODS: Overall, 2906 women were recruited by 64 menopause centres throughout Italy, of whom 2160 filled in the questionnaire (1093 on HRT and 1067 not on HRT; response rate: 74%). RESULTS: HRT users tended to be younger, healthier and with shorter menopause duration as opposed to non users, while no major socio-economic differences were present. At multivariate analysis, the presence of chronic diseases, low socio-economic status and living in Southern Italy represented the most important predictors of poor QoL. Furthermore, HRT users showed a lower probability of reporting problems in usual activities and pain/discomfort (EQ-5D), role limitations due to emotional problems (SF-36) and anxiety/fears (WHQ). HRT users also showed highly significant better outcomes in those areas that are more directly attributable to hormonal changes of mid age, namely vasomotor symptoms and sexual problems. CONCLUSIONS: Although QoL is mainly influenced by socio-economic and cultural factors, HRT has the potential for improving not only symptoms, but also more general aspects of physical and psychological well-being of symptomatic postmenopausal women.
Estrogen Replacement Therapy↗
Reversible increase of serum activin A levels in women with Graves' disease.
The aim of this study was to analyze the serum levels of activin A in hyperthyroid patients with Graves' disease. Serum activin A and FSH levels were measured in a total of 93 females (64 regularly cycling and 29 post-menopausal). Of these, 20 were hyperthyroid patients with Graves disease, 33 were euthyroid goitrous patients (20 had autoimmune thyroiditis AT and 13 only had goiter) representing the internal control group and 40 were healthy subjects representing the external control group. Serum levels of activin A were higher in goitrous patients with AT than in control subjects (p=0.0388). Activin A levels were almost doubled in the cycling and in post-menopausal hyperthyroid women (0.91+/-0.21 vs 0.43+/-0.07 microg/l; p<0.0001 and 0.92+/-0.22 vs 0.48+/-0.24 microg/l; p=0.0001, respectively). In 10 cycling hyperthyroid patients, studied even after methimazole treatment, that increase was substantially reversed, once euthyroidism was attained (p=0.002). These findings indicate that thyroid function and autoimmune processes significantly affect serum levels of activin A in patients with Graves' disease.
Activins↗
Corticotropin-releasing factor, urocortin and endothelin-1 stimulate activin A release from cultured human placental cells.
Human placenta produces activin A, a glycoprotein belonging to the transforming growth factor beta superfamily, which modulates several placental immune and endocrine functions. However, substances involved in controlling placental activin A production are not yet completely elucidated. The aim of the present study was to investigate the effects of placental products, corticotropin-releasing factor (CRF), urocortin, prostaglandin E(2) (PGE(2)) and endothelin-1 (ET-1) on activin A release from cultured human placental cells. Placental tissue was collected at term from normal pregnancies and a trophoblast-enriched cell preparation was cultured for 48 h. The test substances were applied (concentration from 10(-9)-10(-7)M) and the medium was harvested after 3 h incubation; vehicle-treated cells (controls) were present in each experiment. Activin A concentrations in culture medium were measured by using a specific two-site enzyme immunoassay. The addition of CRF resulted in a dose-related increase of activin A concentrations (P < 0.01). The stimulatory effect of CRF was significantly reversed by alpha-helical CRF(9-41), the CRF receptor antagonist. Urocortin showed a stimulating effect on activin A release from placental cells (P < 0.05) but not dose-related; the effect of urocortin was reversed by an equimolar dose of CRF antagonist, astressin. ET-1 significantly increased activin A concentrations in the culture medium only at the highest concentration, 10(-7)M (P < 0.05). No difference in activin A release was observed after incubating the cells with PGE(2). The evidence that CRF, urocortin and ET-1 stimulate activin A secretion from cultured placental cells suggests that these vasoactive factors may affect the changes of placental activin A secretion in pre-eclamptic woman.
Activins↗
Reduction of steps in the preparation of motile sperm for intrauterine insemination does not reduce efficacy of the procedure: simplified one-step swim-up method versus classic swim-up.
BACKGROUND: Intrauterine insemination (IUI) is a valid treatment for infertility with a cumulative pregnancy rate of >40-90% after 3-10 treatment cycles. We studied the efficacy of a simplified method for motile sperm preparation for IUI. METHODS: A prospective clinical trial was performed with 100 couples (male age 33-48 and female 28-37 years) with a 2-8 year history of primary infertility associated with slight oligozoospermia (16/100), oligomenorrhoea (32/100) or unknown (52/100). Motile sperm for IUI were prepared by: (A) the classic World Health Organization self-migration (swim-up) method which includes centrifugation, or (B) a simplified one-step swim-up procedure without centrifugation. Recombinant FSH was used for ovarian stimulation. Depending on the cause of infertility, patients were matched one-to-one at the time of IUI, so that when a total of 100 couples had been treated, 50/100 women received sperm prepared by method A and 50/100 by method B. RESULTS: A statistically significant correlation was found between the percentage motile sperm of the original semen sample and the percentage of motile sperm recovered by method A (r = 0.333, P < 0.01) and B (r = 0.400, P < 0.01). A highly significant correlation (r = 0.997, P < 0.001) was found between the two methods. CONCLUSIONS: The simplified one-step swim-up method was as effective as the classic swim-up method, but the former was easier and more economical.
Adult↗
High serum allopregnanolone levels in girls with precocious puberty.
Allopregnanolone, a circulating neuroactive steroid hormone, is involved in the modulation of behavioral functions, stress, and the neuroendocrine axis. The aim of this study was to evaluate serum allopregnanolone concentrations in girls with central precocious puberty (n = 12), girls with normal pubertal development at the same pubertal stage (n = 17), and prepubertal girls (age-matched; n = 16). Gonadotropin and steroid hormones (allopregnanolone, cortisol, dehydroepiandrosterone sulfate, and E2) were assessed in all patients. GnRH and ACTH stimulation tests were performed in all girls with central precocious puberty and in some pubertal controls. Basal allopregnanolone levels in girls with central precocious puberty were significantly higher than in normal controls (P < 0.01). Allopregnanolone levels increased significantly after GnRH and ACTH stimulation tests (P < 0.05) both in girls with central precocious puberty and in those with normal pubertal development. There was no difference found between the peak values. In conclusion, our study shows that allopregnanolone is hypersecreted in central precocious puberty, confirming a pubertal stage-related increase in its levels during normal pubertal development. The increase in serum allopregnanolone after GnRH and ACTH stimulation tests demonstrates that both adrenal cortex and gonads are sources of this neuroactive steroid.
Adrenocorticotropic Hormone↗
Identification of urocortin mRNA and peptide in the human endometrium.
Urocortin is a 40-amino acid peptide belonging to the corticotropin-releasing factor (CRF) family. In human reproductive tissues, urocortin expression has been previously demonstrated in the ovary, in the placenta and fetal membranes and in pregnant uterine tissues, while no data are available on the expression of the peptide in the nonpregnant uterus. In this study, urocortin expression was evaluated by both immunohistochemistry and reverse transcription-polymerase chain reaction, in human uterine tissues and cells at different phases of the menstrual cycle. Urocortin was immunolocalized in endometrial epithelial and stromal cells, as well as in the myometrium, and in vascular smooth muscle cells. No differences between proliferative and secretory phase were observed. These results were confirmed by reverse transcription-polymerase chain reaction analysis of isolated endometrial epithelial and stromal cells, and myometrial specimens. These findings open new questions on the roles played by urocortin in the human uterus.
Corticotropin-Releasing Hormone↗
Validation of Italian version of the Women's Health Questionnaire: assessment of quality of life of women from the general population and those attending menopause centers.
OBJECTIVES: The Women's Health Questionnaire has been developed and validated in Anglo-Saxon and Swedish populations. The purpose of this study was to evaluate the Italian version of the questionnaire to determine whether cross-cultural differences exist in the perception of quality of life, and to use it to compare the quality of life in women attending menopause centers with that of women in the general population. METHODS: An Italian version of the Women's Health Questionnaire (WHQ) was produced, using the forward-backward translation method to ensure conceptual equivalence, and approved by the originator. Women were recruited by random selection from the general population and from menopause centers, those taking hormone replacement therapy being ineligible. The questionnaire was completed anonymously at home and mailed to the co-ordinating center. Psychometric evaluation included tests of item convergent and discriminant validity, internal-consistency reliability, test-retest reliability, construct validity and the discriminative properties of the questionnaire. RESULTS: The completeness of the data was good, with missing-value rates consistently low for most items. Item-scale correlations, used to evaluate internal consistency, were also good and the scaling success rate, used to measure item discriminant validity, was high for all scales. Scale scores were reliable for seven out of nine scales and test-retest reliability was excellent. There were few significant differences between the two populations of women in most of the WHQ areas. A comparison of Italian data with published data on English women showed great similarity. CONCLUSION: The Italian version of the WHO is valid and reproducible. The subjective perception of the menopause and its related problems is similar in geographically and culturally different populations.
Affect↗
Indication of hysteroscopy in tamoxifen treated breast cancer patients.
The aim of this study was to indicate the patients treated with tamoxifen for breast cancer in which hysteroscopy with biopsy should be considered mandatory. 414 breast cancer patients who underwent hysteroscopy with bioptic evaluation were enrolled in the study. 334 subjects were treated with 20 mg of tamoxifen daily as adjuvant therapy for six up to a hundred months. Of the remaining 80 control patients, which had not received tamoxifen, 30 were in premenopause (Group IA) and 50, in postmenopause (Group IIA). The tamoxifen-treated patients were subdivided in premenopausal (Group IB = 72 patients) and in postmenopausal (Group IIB = 262 patients) groups. All patients were further classified in asymptomatic or symptomatic groups considering whether uterine bleeding was absent or present. The evaluation of the endometrial mucosa was performed by office hysteroscopy. In group IIB patients presenting uterine bleeding, malignant lesions were found in 7.8% of the cases. The incidence of premalignant and malignant lesions in IIB patients treated for longer than 3 years (11.7%) was higher than that observed in IIB patients treated for less than 3 years (1.3%). There was a significant difference in terms of endometrial pathology between Group IIB (32.8%) and Group IIA (8%) (p < 0.001); and between Group IIB (32.8%) and Group IB (13.9%) women (p = 0.003). Among IA and IIA patients there were no cases of endometrial hyperplasia or cancer; on the contrary, in IB and IIB women, 2 and 22 cases of atypical hyperplasia were observed, respectively. All cases of endometrial cancer were observed in Group IIB and had a diagnosis of poor prognosis. In conclusion the hysteroscopy with biopsy should be considered the first diagnostic procedure to perform in tamoxifen-treated postmenopausal patients presenting uterine bleeding and in postmenopausal women treated for longer than 3 years. In premenopause, hysteroscopy should be proposed to women with ultrasonographic abnormalities and/or with uterine bleeding to patients at high risk for endometrial cancer.
Antineoplastic Agents, Hormonal↗
Pre-eclampsia with fetal growth restriction: placental and serum activin A and inhibin A levels.
Activin A (beta A beta A) and inhibin A (alpha beta A) are dimeric glycoproteins secreted from early to term pregnancy in the maternal circulation. They circulate in higher amounts in women with gestational hypertension and/or pre-eclampsia, the most important gestational diseases also causing fetal growth restriction (FGR). Since no data are available in patients with pre-eclampsia and superimposed FGR, by using two-site immunoassays we evaluated serum activin A and inhibin A levels in serum samples collected from: healthy normotensive pregnant controls (n = 42); and women with pre-eclampsia with (n = 19) or without superimposed FGR (n = 21). In addition, by quantitative reverse transcriptase-polymerase chain reaction the changes of alpha- and beta A-subunit mRNA expression in placentas collected from healthy controls (n = 7) and pre-eclamptic pregnancies with (n = 6) or without (n = 6) superimposed FGR was also investigated. Activin A and inhibin A serum levels were significantly higher in pre-eclampsia, and the presence of FGR did not significantly modify these concentrations. Similarly, inhibin-subunit mRNA levels in placentas from pre-eclampsia were significantly higher than in controls, and FGR did not significantly affect this expression. The present data suggest that the increased placental expression of inhibin subunit mRNAs is part of the mechanism leading to increased serum activin A and inhibin A levels.
Activins↗
Ovarian hyperstimulation-like syndrome after administration of triptorelin to a woman with endometriosis.
Ovarian hyperstimulation after a single dose of gonadotropin-releasing hormone (GnRH) analog is a rare phenomenon. A case of ovarian hyperstimulation-like syndrome after sole administration of triptorelin (Decapeptyl 3.75 mg) is reported in a woman who had undergone surgery for an endometriotic cyst. After administration of the drug, abdominal pressure increased with nausea and diffuse pelvic pain. Ultrasound examination showed bilateral enlargement of the ovaries (right 74 x 62 mm, left 62 x 53 mm), more than 10 follicles ranging in diameter from 15-25 mm, proliferative endometrium 7 mm thick and fluid in the Douglas pouch up to 25 x 23 mm thick. Estradiol plasma level was in the normal range. The syndrome spontaneously resolved in the course of treatment and a spontaneous pregnancy occurred when the triptorelin effect disappeared.
Adult↗
Evaluation of combining kava extract with hormone replacement therapy in the treatment of postmenopausal anxiety.
OBJECTIVE: to evaluate the efficacy of combining kava extract with hormone replacement therapy in the treatment of menopausal anxiety. MATERIALS AND METHODS: HAMA score was evaluated before and after therapy in four groups of women in menopause (duration of menopause ranged from 1 to 12 years). The groups were treated with hormone replacement therapy (with and without progestogens) and kava extract or placebo for 6 months. RESULTS: A significant reduction in HAMA score was observed in all four groups of women. The reduction was more significant in groups taking kava extract than in groups on hormones only. DISCUSSION: The combined use of hormone replacement therapy and kava extract seems to be effective against menopausal anxiety. Kava extract accelerates resolution of psychological symptoms while hormone therapy safeguards against osteoporosis and cardiovascular disease.
Anxiety↗
Changes in inhibins and activin secretion in healthy and pathological pregnancies.
Inhibin-related proteins are involved in the control of the feto-maternal communication required to maintain pregnancy. Human placenta, decidua, and fetal membranes are the major sites of production and secretion of activin A, inhibin A and inhibin B in maternal serum, amniotic fluid, and cord blood. The availability of suitable assays developed in the last years has enabled the measurement of inhibins and activin A in their dimeric forms, in order to investigate their role in physiological conditions of pregnancy. The studies conducted on inhibin-related proteins and human pregnancy suggested the possibility of an involvement of inhibin A and activin A in the pathogenesis of gestational diseases. In fact, several lines of evidence underline the potential role and the clinical usefulness of inhibin-related proteins measurement in the diagnosis, prevention, prognosis and follow-up of different gestational pathologies such as early pregnancy viability, Down's syndrome, fetal demise, pre-eclampsia, pregnancy-induced hypertension, preterm delivery and intrauterine growth restriction. The measurement of inhibin A and activin A into the biological fluids of pregnancy will offer in the future, further possibilities in the early diagnosis, prediction, and monitoring diseases of pregnancy.
Activins↗
Evaluation of plasma levels of renin-aldosterone and blood pressure in women over 35 years treated with new oral contraceptives.
Increases in blood pressure and weight are consequences of increased fluid retention following oral contraceptives administration. Hypertension and weight increase are particularly frequent in women over 35 years of age. The aim of the present study was to evaluate the clinical and hormonal effects of a new extra-low dose oral contraceptive [15 microg ethinyl estradiol (EE) and 60 microg gestodene (GSD)] on the renin-aldosterone system in a group of women aged 35-39 years treated for 3 months compared with a formulation containing the same hormones at a higher dose. Eighteen healthy women, age 35-39 years, were divided into two groups. The first group (10 women) used Arianna, Schering, 15 microg EE/60 microg GSD (EE15/GSD60); the second group (8 women) used Fedra, Schering, 20 microg EE/75 microg GSD (EE20/GSD75). Blood samples were obtained before the study and after 3 months of contraceptive use for assay of renin and aldosterone. Blood pressure was also measured on both occasions. No significant changes in plasma renin activity (PRA) or plasma concentrations of aldosterone were observed between the two groups after 3 months of contraceptive use. The mean increase in body weight after 3 months of contraceptive use was 350 +/- 100 g for EE20/GSD75 and 300 +/- 50 g for EE15/GSD60. There was a mean increase of 4 mm Hg for systolic pressure and 2 mm Hg for diastolic pressure in women on EE20/GSD75 and corresponding increases of 3 and 2 mm Hg in women on EE15/GSD60. The changes were not significant in any case. The results of the present study show that the formulations were well tolerated and provided good control of the menstrual cycle in all 18 women. The contraceptive formulations EE20/GSD75 and EE15/GSD60 have no clinical impact on blood pressure, PRA, or aldosterone in this age group.
Adult↗
Evidence for local production of inhibin A and activin A in patients with ovarian endometriosis.
OBJECTIVE: To evaluate the expression of inhibin A and activin A in ovarian endometriosis. DESIGN: Uncontrolled cross-sectional study and controlled prospective in vitro study. SETTING: Academic health centers in Siena, Udine, Sassari, and Milan, Italy. PATIENT(S): A group of women (n = 19) who underwent laparoscopic excision of ovarian endometriotic cysts. INTERVENTION(S): Specimens of serum, peritoneal fluid, and cystic fluid, ovarian tissue for immunohistochemistry, and endometriotic cells for primary culture were collected. Cell cultures were also prepared from proliferative endometrium of women without endometriosis. MAIN OUTCOME MEASURES: Dimeric inhibin A and activin A concentrations in biological fluids; immunostaining of alpha and betaA subunits in ovarian endometrioma; alpha and betaA gene expression in cultured endometriotic cells compared with normal endometrium. RESULT(S): Inhibin A and activin A concentrations in the cystic fluid were slightly higher than in peritoneal fluid and significantly higher than in serum (P<.05). Immunoreactive alpha and betaA subunits were strongly expressed both in the epithelial and stromal components of ovarian endometrioma. The relative abundance of betaA mRNA was significantly decreased in endometriotic cells compared with eutopic stromal cells. CONCLUSION(S): The results of the present study provide evidence for a local production and secretion of inhibin A and activin A in ovarian endometriotic cysts.
Activins↗