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The prognostic value of serum inhibin, 17 beta-estradiol and progesterone in cases of hydatidiform mole.

The purpose of this study was to provide a diagnostic and a prognostic variable that could easily be measured in the laboratory, and that would predict the need for future therapy of persistent gestational trophoblastic disease. There would no longer be a need to treat all cases of hydatidiform mole prophylactically, to improve the outcome in only about 20% predicted to develop malignant gestational trophoblastic tumors. Circulating beta-human chorionic gonadotropin (beta-hCG), progesterone, 17 beta-estradiol and inhibin levels were measured using standard radioimmunoassays in 60 patients with complete hydatidiform mole and in 20 normal pregnant women of a corresponding duration of pregnancy and having a maternal indication for therapeutic abortion. There were no significant statistical differences between the two groups as regards gravidity, parity and gestational age. There was a significant statistical difference between patients with a molar pregnancy who developed gestational trophoblastic tumors (GTT) and those who did not develop GTT as regards pre-evacuation and follow-up mean serum beta-hCG, mean serum progesterone and mean serum 17 beta-estradiol levels. These findings together with the persistently elevated mean serum progesterone and mean serum 17 beta-estradiol levels at 6 weeks after evacuation in all cases who developed GTT suggested that progesterone as well as 17 beta-estradiol serum levels might be of prognostic value in cases of molar pregnancy. However, larger numbers of cases are required to correlate findings to beta-hCG serum level. Although mean serum inhibin level was significantly higher in women with hydatidiform mole than in normal pregnant women, it lacks any prognostic value for detection of subsequent gestational trophoblastic tumors.

Adult↗

Transdermal 17β-Estradiol for the Treatment of COVID-19: Protocol of an Early Terminated Phase 2 Randomized Controlled Trial.

BACKGROUND: Early epidemiological studies suggested that pre- and postmenopausal women receiving estrogen therapy were less likely to develop severe disease or die from COVID-19 infection. Potential mechanisms include estrogen-mediated immunomodulation and 17β-estradiol-induced downregulation of angiotensin-converting enzyme type 2 (ACE2), the cellular receptor for SARS-CoV-2. OBJECTIVE: This study aimed to evaluate the feasibility, safety, and preliminary efficacy of transdermal 17β-estradiol as an adjunctive treatment for COVID-19 in men and postmenopausal women. METHODS: We designed and conducted a randomized controlled trial comparing 17β-estradiol transdermal gel plus standard care with standard care alone in adults with confirmed COVID-19. Initial ethics and funding approvals were obtained in March 2021. Owing to changes in the epidemiology of COVID-19 in Qatar and revisions to national quarantine policies, protocol amendments were required before recruitment commenced in February 2022. The treatment duration was reduced from 10 to 7 days due to changes in national quarantine guidelines. Recruitment and follow-up were conducted between February 2022 and June 2022. RESULTS: Recruitment was substantially lower than anticipated because widespread COVID-19 vaccination, declining disease severity, and revised national quarantine policies markedly reduced the number of eligible hospitalized patients. Consequently, the planned sample size was not achieved, and the study was terminated in June 2022. A total of 29 men with mild COVID-19 were enrolled, with 44.8% (n=13) randomized to standard care and 55.2% (n=16) to transdermal 17β-estradiol plus standard care. The intervention was well tolerated, with no adverse safety signals or thromboembolic events reported. CONCLUSIONS: Although the study was underpowered to assess efficacy because recruitment targets were not achieved, it showed that transdermal 17β-estradiol was well tolerated, with no major safety concerns among enrolled participants. The experience also provided important operational lessons for conducting clinical trials during rapidly evolving pandemics. Adequately powered studies are required to determine whether transdermal estrogen has therapeutic potential against COVID-19, other ACE2-mediated coronavirus infections, or potentially other severe viral illnesses.

Humans↗

Pharmacology and toxicology of ethinyl estradiol and norethindrone acetate in experimental animals.

For over 30 years various combinations of synthetic estrogens and progestins have been used in oral contraceptive formulations. Ethinyl estradiol (EE) and norethindrone acetate (NA) are common synthetic hormones used in oral contraceptives such as Loestrin, Brevicon, Ortho-Novum, Norlestrin, and Norinyl. In recent years these oral contraceptives have been considered for development in other therapeutic indications. Given the use of these agents for other clinical indications with different and larger target populations, an updated comprehensive review of the toxicology literature of estrogens and progestins is warranted. This review will summarize available data on the pharmacology and toxicology of estrogens and progestins with an emphasis on the specific synthetic hormones EE and NA. Ethinyl estradiol and norethindrone acetate alone or in combination, possess low acute and chronic toxicity. In some studies, EE and/or NA increased the incidence of specific tumors in susceptible strains of rodents and dogs, but not monkeys. These agents are not teratogenic when given in combination. Alone EE and NA have clastogenic properties. Overall, the animal data demonstrates that long-term exposure to EE and NA formulations pose very little health risks to humans.

Animals↗

[Experimental study on regulatory effect of compound gengniankang on endocrine and immune functions in aged female rats with osteoporosis].

OBJECTIVE: To observe the effect of compound gengniankang (GNK) in regulating the endocrine and immune functions in aged female rats. METHODS: Aged female rats with osteoporosis were selected as the object for observation and healthy young rats were taken for control. Animals were administered by GNK and nilestriol respectively, through gastric perfusion, for 3 months to observe the therapeutic effect of drug treatment on osteoporosis and the regulatory effect on endocrine and immune function. Bone mineral density (BMD) was measured by double energy X-ray absorption technique, serum levels of estradiol (E2), follicule-stimulating hormone (FSH) and luteinizing hormone (LH) were determined by RIA, T-cell subsets and apoptosis in spleen were detected by flow cytometry. RESULTS: In aged rats with osteoporosis, the BMD decreased, serum level of E2 lowered, FSH and LH levels raised, splenic CD4+, CD4+/CD8+ significantly decreased and T-cell apoptosis rate significantly elevated. GNK could increase the BMD, lower the FSH and LH levels, but showed no significant effect on E2 level. It could increase the CD4+ and CD4+/CD8+ ratio to nearby the normal range, and reduce the apoptosis of T-cells. CONCLUSION: GNK has therapeutic effect on osteoporosis in aged rats, and is able to regulate the endocrine and enhance the immune function in organism.

Absorptiometry, Photon↗

Vascular endothelial growth factor production and regulation in rodent and human pituitary tumor cells in vitro.

Angiogenesis, the formation of a new blood supply, is an essential step in tumorigenesis. Although vascular endothelial growth factor (VEGF) is known to be a very potent angiogenic factor in most solid tumors, little is known about its production and regulation in pituitary adenomas. We have investigated basal and stimulated VEGF production by rodent pituitary tumor cells (mouse corticotrope AtT20, rat lactosomatotrope GH3, mouse gonadotrope alpha T3-1 and mouse folliculostellate TtT/GF cells), and by hormone-inactive (27), corticotrope (9), lactotrope (3) and somatotrope (21) human pituitary adenoma cell cultures. All 4 pituitary cell lines secreted VEGF, which in the case of AtT20, GH3 and TtT/GF cells was inhibited by approximately 50% by dexamethasone. TtT/GF cells were the most responsive to the different stimuli used since basal values were augmented by pituitary adenylate cyclase activating polypeptide-38 (PACAP-38), interleukin-6 (IL-6), transforming growth factor-alpha (TGF-alpha), IGF-I and the somatostatin analogue ocreotide. However, in GH3, AtT20 and alpha T3-1 cells, basal VEGF levels where not enhanced with any of the stimuli tested. The majority of the human adenomas tested (92%) basally secreted measurable VEGF which was inhibited by dexamethasone in most cases (84%). VEGF levels were increased in hormone inactive adenomas, somatotrope tumors and prolactinomas by TGF-alpha, PACAP-38, and 17 beta-estradiol, respectively. In conclusion, pituitary tumor cells are capable of producing VEGF which may be involved in tumoral angiogenesis. Our results concerning the suppression of VEGF by dexamethasone suggest that glucocorticoids may have anti-angiogenic properties and therefore therapeutic relevance for the treatment of pituitary adenomas.

Adenoma↗

Benefits of resveratrol in women's health.

Resveratrol and trans-resveratrol are powerful phytoestrogens, present in the skins of grapes and other plant foods and wine, which demonstrate a broad spectrum of pharmacological and therapeutic health benefits. Phytoestrogens are naturally occurring plant-derived nonsteroidal compounds that are functionally and structurally similar to steroidal estrogens, such as estradiol, produced by the body. Various studies, reviewed herein, have demonstrated the health benefits of phytoestrogens in addressing climacteric syndrome including vasomotor symptoms and postmenopausal health risks, as well as their anticarcinogenic, neuroprotective and cardioprotective activities and prostate health and bone formation promoting properties. Conventional HRT drugs have been demonstrated to cause serious adverse effects including stroke and gallbladder disease, as well as endometrial, uterine and breast cancers. Recent research demonstrates that trans-resveratrol binds to human estrogen receptors and increases estrogenic activity in the body. We investigated the effects of protykin, a standardized extract of trans-resveratrol from Polygonum cuspidatum, on cardioprotective function, the incidence of reperfusion-induced arrhythmias and free radical production in isolated ischemic/reperfused rat hearts. The rats were orally treated with two different daily doses of protykin for 3 weeks. Coronary effluents were measured for oxygen free radical production by electron spin resonance (ESR) spectroscopy in treated and drug-free control groups. In rats treated with 50 and 100 mg/kg of protykin, the incidence of reperfusion-induced ventricular fibrillation was reduced from its control value of 83% to 75% (p < 0.05) and 33% (p < 0.05), respectively. Protykin was seen to possess cardioprotective effects against reperfusion-induced arrhythmias through its ability to reduce or remove the reactive oxygen species in ischemic/reperfused myocardium. Taken together, these data suggest that trans-resveratrol supplementation may be a potential alternative to conventional HRT for cardioprotection and osteoporosis prevention and may confer other potential health benefits in women.

Animals↗

Bromocryptin and epimestrol in MAP-negative secondary amenorrheas.

18 patients, between 18 and 24 years of age, affected by normoprolactinemic secondary amenorrhea and still MAP-negative after three successive Epimestrol cycles underwent five cycles of a combined treatment (Bromocryptin and Epimestrol). Before and after the first cycle of combined treatment, in all patients FSH, LH, E2 and PRL were measured. Progesterone was evaluated three days after the thermic rise. The basal temperature was measured daily. In all the examined patients the combined treatment produced the appearance of the menstrual flow after the third therapeutical cycle. In 13 out of the 18 examined patients ovulation was observed. The hormonal dosage highlighted a clear increase in Gonadotropins and Estradiol levels.

Adolescent↗

Formestane. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the management of breast cancer and prostatic cancer.

Formestane (4-hydroxyandrostenedione) is an effective and competitive inhibitor of aromatase, the enzyme responsible for the conversion of androgens to estrone and estradiol. Significant reductions in plasma estradiol levels are observed following intramuscular administration of formestane to postmenopausal women with advanced metastatic breast cancer. Overall response rates to intramuscular formestane in these patients are approximately 25 to 30% and a further 20 to 30% of patients experience disease stabilisation during treatment. Response rates are improved in patients with hormone responsive tumours and in those who have responded to previous endocrine therapy. Soft tissue metastases generally show the best response to formestane treatment while visceral metastases (in particular liver) show a poor response. The median duration of response is usually between 7 months and 1 year. Formestane has been generally well tolerated in the relatively small clinical trials conducted to date with adverse effects reported in approximately 13% of patients following intramuscular administration. The most frequent adverse effects are local reactions at the injection site and systemic effects mainly related to the effect of the drug on the hormonal milieu. Thus, formestane is effective as a second-line endocrine treatment for advanced metastatic breast cancer in women with natural or artificially induced menopause, with apparent tolerability advantages over older agents such as aminoglutethimide; with wider study and experience it may yet challenge tamoxifen as a first-line endocrine therapy in metastatic breast cancer.

Androstenedione↗

[Therapeutic use of a gonadotropin releasing hormone analogue in breast cancer].

Superagonistic analogues of Gn-RH given chronically produce a paradoxic inhibition of pituitary gonadotropin secretion and consequently decrease the peripheric hormones estradiol and progesterone to a postmenopausal level. For curative purposes buserelin (SuprefactR, Hoechst) treatment has been performed by the authors in two cases of breast cancer. The patients--one with NED (no evidence of disease) and the other with pulmonary and osseal metastases--in addition to low hormonal levels developed amenorrhoea. A group of climacteric complaints were observed without any toxic side effects, however. The treatment of premenopausal women suffering from breast cancer with chronic administration of Gn-RH analogues may constitute a valuable alternative to surgical oophorectomy.

Breast Neoplasms↗