High Estrogen Environment Research Articles

Estrogen–progestagen pre-treatment before HMG induction in hypogonadotropic patients

Hypogonadotropic patients are candidates for ovulation induction when they desire fertility. This study aims to evaluate the effect of estrogen-progestagen combination pretreatment before ovulation induction by human menopausal gonadotropins. 30 infertile hypogonadotropic patients with no other pathological findings that might cause infertility except for anovulation participated in the study. After 3 months of pretreatment patients were given hMG monthly for at least four cycles unless pregnancy was achieved. 8 patients were lost to follow-up during the study period; the remaining 22 subjects who were pretreated with the estrogen-progestagen combination underwent a total of 63 cycles of hMG-hCG induction and all achieved pregnancy by the fourth cycle. It was observed that estrogen-progestagen pretreatment before hMG induction may result in higher ovulatory and pregnancy rates in hypogonadotropic patients probably due to a high estrogenic environment and new steroid receptor formation.

Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumorigenesis in female rat offspring.

A high estrogenic environment in utero may increase subsequent breast cancer risk. It was therefore determined whether a maternal exposure during pregnancy to the phytoestrogen genistein or zearalenone, both of which exhibit estrogenic activities in vitro and in vivo, alters breast cancer risk among female offspring. Pregnant rat dams were treated daily with subcutaneous injections of 20, 100 or 300 microgram genistein, 20 microgram zearalenone, or vehicle between days 15 and 20 of gestation. The offspring were given 7, 12-dimethylbenz(a)anthracene (DMBA) at the age of 2 months to induce mammary tumors. The results indicate that in utero exposure to genistein, but not to zearalenone, dose-dependently increased the incidence of DMBA-induced mammary tumors, when compared with the controls. Tumor growth characteristics were not altered. Prior to the carcinogen administration, the number of estrogen receptor (ER) binding sites, determined using a ligand binding assay, were significantly elevated in the mammary glands of genistein offspring. In contrast, the mammary protein kinase C (PKC) activity was significantly reduced in the genistein offspring. Our results suggest that a maternal exposure to subcutaneous administration of genistein can increase mammary tumorigenesis in the offspring, mimicking the effects of in utero estrogenic exposures. Further, increased ER protein levels and reduced PKC activity in the mammary gland may be involved in increasing susceptibility to carcinogen-induced mammary tumorigenesis in rats exposed to genistein in utero.

The influence of maternal diet on breast cancer risk among female offspring.

The induction of breast cancer is a long process, containing a series of biological events that drive a normal mammary cell towards malignant growth. However, it is not known when the initiation of breast cancer occurs. One hypothesis is that a high estrogenic environment during the perinatal period increases subsequent breast cancer risk. There are many sources of extragonadal estrogens, particularly in the diet. The purpose of this paper is to review the evidence that a high maternal intake of dietary fats increases serum estrogens during pregnancy and increases breast cancer risk in daughters. Our animal studies show that a high maternal consumption of corn oil consisting mainly of linoleic acid (omega-6 polyunsaturated fatty acid, PUFA), increases both circulating estradiol (E2) levels during pregnancy and the risk of developing carcinogen-induced mammary tumors among the female rat offspring. A similar increase in breast cancer risk occurs in female offspring exposed to injections of E2 through their pregnant mother. Our data suggest that the mechanisms by which an early exposure to dietary fat and/or estrogens increases breast cancer risk is related to reduced differentiation of the mammary epithelial tree and increased number of mammary epithelial cell structures that are known to the sites of neoplastic transformation. These findings may reflect our data of the reduced estrogen receptor protein levels and protein kinase C activity in the developing mammary glands of female rats exposed to a high-fat diet in utero. In summary, a high dietary linoleic acid intake can elevate pregnancy estrogen levels and this, possibly by altering mammary gland morphology and expression of fat- and/or estrogen-regulated genes, can increase breast cancer risk in the offspring. If true for women, breast cancer prevention in daughters may include modulating the mother's pregnancy intake of some dietary fats.

Influence of Hormonal Events on Disease Expression in Patients with the Combination of Systemic Lupus Erythematosus and Rheumatoid Arthritis

The concurrent presence of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) ("rhupus" or "rufus") has been described in the literature. However, it has not been clear to what extent and under what circumstances clinical disease expresssion can undergo transitions from one disease to the other. We postulated that major hormonal events might have an influence on disease expression in such patients and conducted a retrospective study of 1507 patients with RA and 893 with SLE. In this population, 13 patients were identified as having convincing clinical diagnoses of both RA and SLE. Although 6 of these 13 patients had symptoms and signs of RA and SLE concurrently during their entire illness, 7 patients had clearly identifiable transitions from SLE to RA, and in one of these patients the reverse occurred as well. Of the 7 transitions from SLE to RA, 5 were associated with menopause (3 of these patients were receiving hormone replacement therapy) and the other 2 occurred in the postpartum period. The one change from RA to SLE in this series occurred during pregnancy. Thus, pregnancy, the postpartum period, and menopause can modulate disease expression in patients with both SLE and RA. It is speculated that, in patients with an autoimmune predilection, a high-estrogen environment (premenopause, pregnancy) favors the clinical expression of SLE, whereas a low-estrogen environment favors more RA-like disease, possibly because of the immunomodulatory effects of sex-steroids. The clinical implication is that in the management of patients with autoimmune diseases such as SLE and RA, hormonal alterations could result in changes in disease expression that might necessitate changes in treatment.

Puerperal and menstrual psychoses: The proposal of a unitary etiological hypothesis

Puerperal and menstrual psychoses are both uncommon disorders and the occurrence of both in individual patients suggest the possibility of a common underlying pathogenesis. In this paper two cases are reported, the literature is reviewed and a unifying etiological hypothesis is postulated in which precipitous reductions in the brain estrogen environment precipitate episodes of psychosis in predisposed individuals. In the case of puerperal psychosis, estrogen cascade follows a lengthy period of sustained high brain estrogen environment; in menstrual psychosis, it is postulated that the occurrence in at least some cases of anovulatory menstrual cycles, wherein high levels of relatively unopposed estrogens are maintained until the next ovulatory cycle, play a role in priming the central nervous system prior to premenstrual estrogen cascade. Further research in this area using more sensitive techniques to follow hormonal fluctuation and mental state is called for

The use of bovine anti-PMSG serum in beef cattle after PMSG-superovulation.

Thirteen beef cows were superovulated using 4,000 i.u. of pregnant mare serum gonadotrophin (PMSG) on days 9 to 14 of the estrous cycle, followed by two injections of 500 micrograms prostaglandin F2 alpha analogue (PGF2 alpha) 48 and 55 hrs later. Seven of them were injected intramuscularly with bovine anti-PMSG serum 12 hrs after the first signs of estrus. The remaining 6 cows were served as controls and received no antiserum. Peripheral blood concentrations of progesterone (P) and estradiol-17 beta (E2) were compared in relation to the superovulatory responses. The injection of anti-PMSG serum did not significantly affect the numbers of the corpora lutea (CL), the anovulatory follicles and the transferable embryos at 7 to 8 days after superovulatory estrus, but increased the ratio of embryos classified as excellent or good quality. Although the plasma P concentration showed no significant differences between the anti-PMSG-treated and control cows, the plasma E2 concentration displayed a characteristic difference, suppressing the second E2 peak in the anti-PMSG-treated cows. It is concluded that the use of bovine anti-PMSG serum for PMSG/PGF2 alpha-treated cows at 12 hrs after the beginning of the estrus improves the quality of embryos recovered, probably due to inhibition of high estrogenic environment following ovulation.

Stable prolactin level after enhanced estradiol production following dehydroepiandrosterone sulfate

To evaluate whether intravenous injection of dehydroepiandrosterone sulfate (DHEAS), by enhancing estradiol (E2) production, would stimulate prolactin (PRL) secretion in late pregnancy, maternal serum PRL was determined before and 1 to 5 hours after administration of 100 mg of DHEAS in a total of 41 women with normal or complicated late pregnancies (twin pregnancy, pre-eclampsia, intrahepatic cholestasis of pregnancy, diaetes). The basal serum PRL concentration in patients with diabetes was significantly lower than normal. The mean PRL level did not change significantly in any group in spite of the increase in serum E2 levels after the DHEAS injection. The lack of PRL response to a rapid rise in E2 may be due to the maximal inhibition of the PRL-inhibiting factor in the hypothalamus and/or maximal activation of the pituitary lactotrophs occasioned by the high estrogen environment during late pregnancy.