Amount Of Estrogen Research Articles

Estrogen and progesterone receptors in gynecomastia.

The etiology of gynecomastia is unknown. There seems to be no increased incidence of malignancies in patients with idiopathic gynecomastia; however, patients with Klinefelter syndrome exhibit an increased incidence of malignancy. The authors reviewed the results of 34 patients with gynecomastia diagnosed in adolescence who, following initial evaluation, had a mastectomy. The estrogen and progesterone receptors were analyzed in these patients. Three of the patients were diagnosed with Klinefelter syndrome. These three patients exhibited elevated amounts of estrogen and progesterone receptors. None of the patients who were not diagnosed with this syndrome demonstrated significant elevation of their estrogen or progesterone receptors. The presence of elevated estrogen and progesterone receptors in patients with Klinefelter syndrome provides a potential mechanism by which these patients may develop breast neoplasms. The absence of elevated estrogen and progesterone receptors in patients with idiopathic gynecomastia may serve to clarify why these patients' disease rarely degenerates into malignancy.

Aromatase inhibitor and 17alpha-methyltestosterone cause sex-reversal from genetical females to phenotypic males and suppression of P450 aromatase gene expression in Japanese flounder (Paralichthys olivaceus).

The sex of Japanese flounder (Paralichthys olivaceus) is easily altered by water temperature or sex steroid hormone treatment during the period of sex determination. We have previously shown that rearing the genetically female larvae at high water temperature caused the suppression of P450 aromatase (P450arom) gene expression in the gonad and phenotypic sex-reversal of the individuals to males (Kitano et al. 1999. J Mol Endocrinol 23:167-176). In the present study, we show that treatment of genetically female larvae with fadrozole (aromatase inhibitor) or 17alpha-methyltestosterone induces sex-reversal as well as suppression of P450arom gene expression. The effect of fadrozole was counteracted by co-administration of estradiol-17beta. Effective periods for fadrozole treatment to induce sex-reversal were similar to those for high water temperature treatment. RT-PCR did not detect P450arom mRNA in gonad of the sex-reversed, phenotypic males. These results indicate that sex-reversal of the genetically female larvae by aromatase inhibitor (or 17alpha-methyltestosterone) may be due to the suppression of P450arom gene expression and the resultant decrease in the amount of estrogen.

Biology of aromatase in the mammary gland.

While the ovaries are the principal source of systemic estrogen in the premenopausal nonpregnant woman, other sites of estrogen biosynthesis are present throughout the body and these become the major sources of estrogen beyond menopause. These sites include the mesenchymal cells of the adipose tissue and skin, osteoblasts, and perhaps chondrocytes in bone, vascular endothelial and aortic smooth muscle cells, as well as a number of sites in the brain including the medial preoptic/anterior hypothalamus, the medial basal hypothalamus and the amygdala. These extragonadal sites of estrogen biosynthesis possess several fundamental features which differ from those of the ovaries. Principally, the estrogen synthesized within these compartments is probably only biologically active at a local tissue level in a paracrine or 'intracrine' fashion. Thus the total amount of estrogen synthesized by these extragonadal sites may be small, but the local tissue concentrations achieved are probably quite high, and exert significant biological influence locally. Thus these sources of estrogen play an important but hitherto largely unrecognized, physiological and pathophysiological role.

Modus Operandi of an Infamous Drug

First, do no harm. Physicians try to adhere religiously to this creed, but sometimes the best of intentions go awry. In the 1940s, physicians began giving diethylstilbestrol (DES) to pregnant women, several million of them in the United States alone. The first synthetic version of the hormone estrogen, DES was available as a pill, making it an eagerly welcomed drug for the physicians of the time who believed that insufficient amounts of estrogen led to a miscarriage. DES grew so popular that it was even prescribed for pregnant women not at high risk of a miscarriage and for treating conditions such as acne and cancer. Although a study in 1953 concluded that DES didn't reduce the miscarriage rate, and actually seemed to increase it slightly, physicians continued to give the hormone to pregnant women until 1971. That year, another study linked several young women's development of a rare cancer of the vagina and cervix to their DES exposure while in the womb. Seven months after the study's publication, the Food and Drug Administration warned physicians not to prescribe DES to pregnant women. Subsequently, hundreds of cases of the cancer have been attributed to DES exposure. As researchers have followed up on the side effects of the drug, they also have found that women exposed as embryos, the so-called DES daughters, may have abnormally developed reproductive tracts, causing such problems as infertility and miscarriages. Although the evidence isn't as definitive, males exposed to DES in the womb may not have escaped the drug's wrath, either. Some research has indicated that DES sons have a higher-than-normal frequency of reproductive-tract abnormalities but no decreased fertility (SN: 5/27/95, p. 324). Much like thalidomide, another drug that caused unexpected birth defects when given to pregnant women (see sidebar), DES has provided a sobering lesson on the importance of thoroughly testing a drug's safety. Yet, despite realizing that DES exposes the fetus to an unintended flood of estrogen, scientists have remained at a loss to explain exactly how the compound brings about its tragic effects. In the past decade, however, developmental biologists have made great strides

13C]Aminopyrine breath test detects altered liver metabolism caused by low-dose oral contraceptives

The [13C]aminopyrine breath test measures hepatic mixed function oxidase activity. The cumulative percent dose recovered over 2 hr is a sensitive indicator of hepatic dysfunction; values < or = 7.0% have been shown to indicate severe liver disease. Previous studies have suggested that the test results may be influenced by the use of oral contraceptives steroids. We compared the results from five non-oral contraceptive-using women with those from 31 women whose duration of oral contraceptive steroid usage ranged from 4 to 204 months. The women were taking one of four oral contraceptive formulations that differed in the amounts of estrogen (20, 35, or 50 micrograms with 1 mg progesterone) and progesterone (35 micrograms estrogen with stepped levels of progesterone of 0.5, 0.75, and 1.0 mg). The [13C]aminopyrine breath test was performed on days 21 and 28 of the menstrual cycle. Cumulative percent dose recovery values among the normal menstrual cycle of non-oral contraceptive steroid-using women were 12.1 +/- 1.6 and 11.8 +/- 1.5% (mean +/- SD). In contrast, oral contraceptive steroid users showed a marked reduction in cumulative percent dose recovery at 21 days, averaging 6.1 +/- 2.3% (P < 0.001), and returned to normal values (10.2 +/- 3.5%) at 28 days in most women(seven days after oral contraceptive steroid usage was paused). The adverse impact on hepatic mixed function oxidase by oral contraceptive formulations did not differ on the basis of estrogen or progesterone content. The adverse impact of oral contraceptive usage on the mixed function oxidase activity measured by the [13C]aminopyrine breath test must be considered for women of childbearing potential.

Acoustic schwannoma and pregnancy: a DNA flow cytometric, steroid hormone receptor, and proliferation marker study.

For a long time, it has been speculated that pregnancy stimulates the growth of acoustic schwannomas. To test this hypothesis, immunohistochemical stains for estrogen receptor, progesterone receptor, and proliferating cell nuclear antigen (PCNA) were performed. Flow cytometric studies for DNA ploidy and S-phase fraction determinations were also performed. The study subjects included 6 female patients with unilateral acoustic tumors; at the time of tumor removal, 1 woman was pregnant and the other 5 women were 2 to 10 months postpartum. The age-sex-matched control group consisted of 6 men and 12 nonpregnant women, all with acoustic schwannomas similar in size to those of the study group. The study found no statistically significant association between the presence or quantity of estrogen or progesterone receptors and pregnancy, DNA ploidy, proliferation indices, or clinical data. Based on PCNA indices, large tumors tended to be less "biologically active" than small lesions (P < .01). The authors concluded that pregnancy does not significantly stimulate the cellular growth of acoustic schwannomas.

Identification and semiquantification of estrogen and progesterone receptors in pyogenic granulomas of pregnancy

Cases of pyogenic granuloma in pregnant women, nonpregnant women, and men were evaluated for the detection of estrogen and progesterone receptor proteins by immunoperoxidase staining. Immunostaining for estrogen receptors revealed a marked immunoreactivity of the endothelium within lesional tissue and in the overlying mucosal epithelium in many cases. Progesterone receptor immunoreactivity was only present within the epithelium, where it was much less than that of estrogen receptor immunoreactivity in both quantity (proportion of positive cells) and intensity. No characteristic staining pattern or significant quantitative difference among the three study groups could be discerned. These findings suggest that the quantity of estrogen or progesterone receptors in pyogenic granuloma is not the determining factor in the pathogenesis of this lesion. Rather, such a role may be attributed to the levels of circulating hormones. The levels of estrogen and progesterone are markedly increased in pregnancy and could therefore exert a greater effect on the endothelium of the pyogenic granuloma.

Oral Contraceptive Use Does Not Raise Breast Cancer Risk for Women Older Than 40, Canadian Data Show

A recent Canadian study found that a history of oral contraceptive (OC) use does not appear to increase the incidence of breast cancer in women aged 40-69 years old. 607 women with histologically confirmed first occurrences of breast cancer were matched according to age group and neighborhood with 1214 controls. Data on risk factors for breast cancer and on use of OCs noncontraceptive estrogens and other drugs were collected during home interviews during 1982-86. Conditional logistic regression found that longterm use of OCs did not increase the risk of breast cancer in women aged 40 years and over. The under 40 age group consisted of only 80 cases and 160 controls. There were no statistically significant relative risks but the small sample size led the authors to consider their findings in this age group to be inconclusive. The risk of developing breast cancer was not influenced by use of OCs in the recent or distant past. In fact the data suggest that OC may have provided protection against developing breast cancer among older women. The relative risk for women who used OCs for 5 or more years more than 15 years ago was a statistically significant 0.5. There was no correlation between use of OCs before the birth of a first child and breast cancer risk. Nor was there a correlation between the amount of estrogen in the OCs and breast cancer. The validity of these results may have been influenced by a low (65%) participation rate among controls which may have created a selection bias. Also the publicity about OC use and the incidence of breast cancer may have prodded breast cancer patients to remember even a short-term use of OCs.

Oral contraceptive use and risk of benign breast disease in a French case-control study of young women.

We report the results of a French hospital-based case-control study designed to analyse the relation between the use of oral contraceptives (OC) and the risk of benign breast disease (BBD). The cases were 286 women, each less than 46 years old, with BBD histologically verified between 1982 and 1985. Controls were 382 patients, matched to cases on year of birth and month of interview, and who were hospitalized for a non-malignant disease other than BBD. Odds ratios were estimated by multivariate regression, taking into account level of education, place of residence, family history of breast cancer, age at menarche, number of children, age at first full-term pregnancy and Quetelet index. The risk of BBD was found to decrease significantly with a longer use of OC before the first full-term pregnancy (FFTP), but there was no association between the risk of BBD and the duration of OC use after FFTP. OC use before FFTP reduced the risk of non-proliferative disease, but did not significantly affect the risk of proliferative disease. These results did not depend on the amount of oestrogen (0.05 mg or more vs < 0.05 mg) contained in OC.

Comparisons of steroid production and density of LH binding sites in guinea pig ovarian follicles destined to ovulate and destined to become atretic

Two waves of follicular recruitment exist in the 16-day estrous cycle of the guinea pig. One lasts from days 2 to 10 and contains follicles that are all destined to become atretic, while another lasts from days 7 to 16 and includes several follicles destined to ovulate. Healthy-appearing follicles of greater than 0.6 mm were isolated on days 6, 9, and 15 of the cycle to investigate specific characteristics of the two consecutive waves of follicles. Follicles were compared on the bases of LH binding site density and steroid synthetic capacity. Large day-9 and day-15 follicles were shown to have similar densities of LH binding sites and also were capable of synthesizing and secreting large amounts of estrogen following incubation in media supplemented with hCG or testosterone. However, only day-15 large follicles were able to produce large amounts of estrogen in unsupplemented media, which suggests that they had already been exposed to endogenous LH prior to their removal from the ovary. Estrogen production by the large day-9 follicles was negligible when they were incubated in unsupplemented media. These follicles of the first wave of folliculogenesis would not have experienced a similar exposure to endogenous LH in vivo, since it is known that serum concentrations of LH are low during days 6–10 of the cycle. It is postulated that the lower estrogen production by large day-9 follicles may also be associated with the inability to undergo other maturational events essential for ovulation.

Regulation of steroidogenesis of infant and adult rhesus monkey granulosa cells in vitro.

The present studies have demonstrated that infant monkey granulosa cells, like the adult ones, have the potential of responding markedly in vitro to human FSH, cyclic-AMP and forskolin, resulting in the increase of progesterone and estrogen production. Exogenous hCG was also capable of increasing FSH-stimulated progesterone biosynthesis in both infant and adult granulosa cells, but did not stimulate the infant granulosa cells to secrete estrogen. Addition of a synthetic estrogen, diethylstilbestrol, to the culture of monkey granulosa cells enhanced the FSH-stimulated progesterone and estrogen production. The steroidogenesis of monkey granulosa cells was also dramatically stimulated by a gonadotropin-releasing hormone agonist. Monkey granulosa cells, unlike the other animal cells, secrete measurable amount of estrogen in the absence of androgen substrate. The findings reported here are significant in regard to understanding of the mechanism of hormonal regulation of primate ovarian function.

Cyproterone acetate/ethinyl estradiol in the treatment of acne. A comparative dose-response study of the estrogen component

The investigators compared 2 mg cyproterone acetate (CPA) in combination with either 0.035 mg or 0.050 mg ethinyl estradiol (EE 2) (Diane®-35 versus Diane®-50) in the treatment of acne. Both formulations of Diane® were highly effective in improving acne, even in women who had been refractory to other types of medication. Cycle control with both formulations was excellent and adverse effects were generally mild and confined to the first two cycles of treatment. Mean plasma lipid levels increased with both treatments, yet most individual values remained within normal limits after one year of therapy while the LDL-cholesterol/HDL-cholesterol ratio was stable throughout the study period. Plasma testosterone and DHEA-S levels paralleled the decline in the clinical severity of the acne. There was no loss of clinical effectiveness with Diane∗-35 and it provided the advantage of a 30% decrease in the amount of estrogen.

"The Relationship of Tubal Infertility to Barrier Method and Oral Contraceptive Use"

We studied past contraceptive use in 283 nulliparous infertile women who had a diagnosis of tubal adhesions or occlusion and in 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with barrier contraceptive use or oral contraceptive use was calculated using multivariate logistic regression to control for confounding by region, age, religion, education, smoking, number of sexual partners, time since menarche, and use of other contraceptive methods. Women who had ever used barrier methods of contraception were at a significantly decreased risk of tubal infertility (relative risk = 0.6; 95% confidence limits, 0.5 and 0.8). When type of barrier method used for the longest time was evaluated, those who used the diaphragm or condoms plus spermicides were at lower risk than those who used condoms or spermicides alone. Overall, past use of oral contraceptives neither increased nor decreased a woman's risk of tubal infertility, but there was evidence that the association between oral contraceptives and tubal infertility may vary by the amount of estrogen and type of progestogen in the oral contraceptive used. We conclude that contraceptive users who use barrier methods that combine both a mechanical and chemical barrier, such as diaphragms, cervical caps, and condoms plus spermicides, have the clearest protection against tubal damage. (JAMA1987;257:2446-2450)

Effect of massive weight loss on hypothalamic-pituitary-gonadal function in obese men.

To study the ability of weight loss to reverse the hyperestrogenemia-induced hypogonadotropic hypogonadism that occurs in obese men, we measured the 24-h mean plasma free and total estradiol (E2), total estrone, FSH, LH, and free and total testosterone concentrations in 11 healthy obese men (100-305% above desirable body weight) and again 5-39 months later after weight loss of 26-129 kg and restabilization at the new weight. Weight loss produced significant increases in mean plasma total testosterone [240 +/- 116 (+/- SD, 8.5 +/- 4.0) to 377 +/- 113 ng/dL (13.0 +/- 4.0 nmol/L); P less than 0.01], free testosterone [9.5 +/- 5.0 (329 +/- 173) to 13.4 +/- 4.3 ng/dL (464 +/- 149 pmol/L); P less than 0.025], and FSH (6.5 +/- 4.7 to 10.9 +/- 8.5 IU/L; P less than 0.025). Plasma LH was lower than levels in normal men before and after weight loss and did not change significantly (10.3 +/- 4.8 and 10.8 +/- 6.8 IU/L, respectively). There was no change in plasma total E2 [54 +/- 26 (196 +/- 94) to 50 +/- 13 pg/mL (180 +/- 50 pmol/L)], free E2 [1.48 +/- 0.7 (5.37 +/- 2.54) to 1.33 +/- 0.42 pg/mL (4.83 +/- 1.45 pmol/L)], or total estrone [75 +/- 38 (280 +/- 140) to 82 +/- 24 (300 +/- 90) pmol/L], and sex hormone-binding globulin rose from 9.2 +/- 3.2 to 12.9 +/- 5.4 nmol/L (P less than 0.005). The increases in plasma free and total testosterone and sex hormone-binding globulin were proportional to the degree of weight loss. Thus, the hypogonadotropic hypogonadism was largely reversed by the weight loss without any decrease in hyperestrogenemia, its presumed cause. We postulate a change in hypothalamic-pituitary function with weight loss, such that GnRH-gonadotropin secretion becomes less sensitive to suppression by a given amount of estrogen.

Oral contraceptives and venous thromboembolic disease: the effect of the oestrogen dose

Low-dose oral contraceptives when tested for vascular or thrombotic effects not only show no risk of venous thromboembolic disease, but this method could possibly reduce the chance of thromboembolic disease as compared with pills which have a higher estrogen dose. It has also been found that pills containing lower doses of estrogen have no effect on the coagulatory system. Concerns raised about the connection between oral contraceptive use and the risk of cardiovascular disease called for testing in the late 1960s. Epidemiological studies confirmed the risk of oral contraceptive use and cardiovascular disease especially venous thromboembolism. A further association was identified between the amount of estrogens contained in oral contraceptives and the risk of disease. Estrogens affect the hemostatic system; decreases in antithrombin III activity in addition to platelet adhesiveness and blood viscosity have been observed in oral contraceptive users. Although both a decreased influence on the hemostatic system and the risk of thromboembolic disease have been found in pills with lower doses of estrogen, further research on the effect of the clotting system by low-dose oral contraceptives is needed.

The Relationship of Tubal Infertility to Barrier Method and Oral Contraceptive Use

We studied past contraceptive use in 283 nulliparous infertile women who had a diagnosis of tubal adhesions or occlusion and in 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with barrier contraceptive use or oral contraceptive use was calculated using multivariate logistic regression to control for confounding by region, age, religion, education, smoking, number of sexual partners, time since menarche, and use of other contraceptive methods. Women who had ever used barrier methods of contraception were at a significantly decreased risk of tubal infertility (relative risk = 0.6; 95% confidence limits, 0.5 and 0.8). When type of barrier method used for the longest time was evaluated, those who used the diaphragm or condoms plus spermicides were at lower risk than those who used condoms or spermicides alone. Overall, past use of oral contraceptives neither increased nor decreased a woman's risk of tubal infertility, but there was evidence that the association between oral contraceptives and tubal infertility may vary by the amount of estrogen and type of progestogen in the oral contraceptive used. We conclude that contraceptive users who use barrier methods that combine both a mechanical and chemical barrier, such as diaphragms, cervical caps, and condoms plus spermicides, have the clearest protection against tubal damage.

Seminal oestrogens in the boar: Origin and functions in the sow

The boar produces considerable amounts of oestrogens in the Leydig-cells also occurring in semen. Very high oestrogen concentrations are measurable in the fluid of the tubuli, which contribute the main part of seminal oestrogens. Additionally, the accessory sex glands add 22% of the unconjugated oestrogens and 12% of conjugated oestrogens to the ejaculate. Concentrations vary considerably according to season and individuals. So far a maximum of 15.3 μg was measured in one ejaculate. Infusion of oestrogens (simulation of the oestrogen content of an ejaculate) at oestrus through a catheter into the uterus lumen leads to an increase of the myometrial contraction-frequency for 3 h. Additionally “inseminations” with oestradiol-17β (Oe 2), oestrone (Oe 1), and oestrone-sulfate (Oe 1-S) (naturally occurring in the ejaculate) in 10-μg amounts at oestrus may lead to an increase of PGF 2α concentrations in the uterine veins within a few minutes. This increase may be found after “insemination” with each of the three steroids but not after saline. A parallel rise of the “inseminated” oestrogen is measurable in the uterine vein plasma and may reach concentrations up to several thousand pg/ml. This rise also leads to significantly increased concentrations in peripheral plasma for about 30 min after the “insemination” of Oe 2 (increase of Oe 2 and Oe 1-S) and Oe 1 (Oe 1 and Oe 1-S). Consequences of seminal oestrogens for sperm transport and the timing of ovulation are discussed.

The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women

The relationship between diet and estrogens was studied in two groups of women with different dietary habits and breast cancer risks. Plasma estrogens and androgens and 24-h urinary and fecal excretion of estrogens were measured in premenopausal and postmenopausal Caucasians and recent Oriental immigrants from Southeast Asia to Hawaii. Premenopausal Caucasians had 30–75% higher plasma estrone and estradiol levels than their age-matched cohorts in Hawaii, and the postmenopausal Caucasians had 3-fold higher plasma levels of estradiol. The Oriental women excreted more than twice the amount of estrogen in their feces but they excreted significantly less in their urine. Thus, the ratio of urinary-to-fecal excretion was ∼3–5 times higher in young Caucasian women. Analysis of dietary components and plasma estrogens in premenopausal women showed a positive correlation between daily intake of total fat and saturated fat and plasma estrone and estradiol concentrations.

Pharmacokinetics of oral contraceptive steroids in Egyptian women: Studies with ovral, nordette and norminest

Plasma concentration profiles and pharmacokinetic parameters have been obtained following single dos administration of three commonly used oral contraceptive steroid preparations, Ovral, Nordette and Norminest to Egyptian women. The constituents of the preparations are as follows: Ovral (50μg ethinyloestradiol, EE 2 and 500 μg levonorgestrel, LNG); Nordette (30μg EE 2 and 150μg LNG); and Norminest (35μg EE 2 and 500 μg norethisterone, NOR). Peak plasma concentrations of EE 2 ranged between 116–160 pg ml −1 for Ovral, 55–78 pg ml −1 for Norminest and 30–70 pg ml −1 for Nordette. There was no significant difference in half-life ( t 1 2 ), oral clearance (CL) or apparent volume of distribution (Vd). The relative values of the area under the plasma concentration-time curve (AUC) reflected well the different amounts of oestrogen in each preparation. There was no significant difference in ( t 1 2 ), CL or Vd for LNG in the 2 preparations containing this progestogen. The mean AUC following Nordette (150 μg LNG) was 40% of that following Ovral (500 μg LNG; p ⩽ 0.001). Comparing pharmacokinetic parameters for the same dose of LNG (Ovral) and NOR (Norminest) showed the AUC to be decreased and CL and Vd increased in the latter group. The study indicates that the kinetic profile of the OCS in healthy Egyptian women are similar to other ethnic populations.

Comparison of histo- and biochemical methods for estrogen and progesterone receptor analysis in primary human breast carcinoma

One hundred and twenty-three primary breast carcinomas have been examined under optimal procedural conditions for presence and quantity of estrogen (ER) and progesterone (PgR) receptors by a histochemical method using hormones conjugated to fluoresceinated bovine serum albumin and by a conventional biochemical (dextran-coated charcoal) assay. The semiquantitative histochemical results for ER and PgR were strongly positively correlated, as were the corresponding quantitative biochemical results, but there was no significant correlation between histo- and biochemical results for ER, nor between the corresponding results for PgR. By generally accepted cut-off limits for positivity there was an equal frequency of ER- and PgR-positive tumors by the histochemical method ( 71 and 67% respectively), whereas there was a significantly higher frequency of ER- than PgR-positive tumors by the biochemical method ( 76 and 59%). The qualitative agreement between the two methods was 76% for ER and 61% for PgR, and there was a correspondingly inferior sensitivity and specificity of the histochemical method in comparison with the biochemical method, whose value is clinically validated.