dragonfire101 said:
I have seen in studies progesterone levels lower in subjects who used bromocriptine. Dont know if it was because it lowedred prolaction or what?
THREE SUBSTANCES THAT I HAVE SEEN LOWER PROGESTERONE IN STUDIESTwo are drugs
- Mifepristone(ru486)
- Trilostane
One Supplement
- Aqueous Winter Cherry Extract
Reported To Work
-Winstrol
- B6
Actually, most DHT-derived steroids probably act to inhibit progesterone in some way or another. In women, Anadrol (oxymetholone) has even been studied as a possible female contraceptive as well as possible abortion pill, because of it's ability to inhibit progesterone biosynthesis.
Res Front Fertil Regul. 1981 Feb;1(3):1-14.
Inhibition of progestational activity for fertility regulation.
Chatterton RT.
PIP: This review examines a number of areas of postconceptive fertility regulation, focusing on promising new antiprogestational agents. Pregnancy is dependent upon the availability of progesterone for the uterus and its withdrawal results in the breakdown of the secretory endometrium. Its availability can be interferred with at several levels and the new methods which allow for progesterone inhibition must be tested for possible defeminizing properties or for serious side effects. In the evaluation of contragestational agents, several areas must be taken into consideration--assessment of biological activities, dose requirements and mode of action, duration of effects, route of administration, and drug tolerance and side effects. The failure to maintain progesterone in the blood at levels required for pregnancy maintenance may be due to a decrease in progesterone secretion by the ovary or to an increased rate of metabolism and excretion of circulating progesterone. The various substances discussed do either 1 or the other; however even when a compound is known to result in a decrease in the rate of progesterone secretion, the process by which it does this may not be known. Prostaglandins seem to affect myometrial contraction, luteinizing hormone releasing hormones can inhibit steroid production or interfere with LH binding to its receptor, and immunization against hCG is a successful immunological approach to conception. Lithospermic acid is another substance which interferes with gonadotropin support of the ovary and has good potential.
Other compounds that interfere with progesterone secretion act to inhibit steroidogenesis in the ovary and placenta; such substances include aminoglutethimide, oxymetholone, trilostane, azastene, and danazol. Another progesterone-suppression method would remove a sufficient amount of progesterone from the body to cause endometrium involution and promote contractility of the myometrium. Progesterone antagonists include ORF 9361, R3434, Anordrin, ORF 3858, and other estrogens, triazole compounds, ORF 5513, trichosanthin, and zoapatanol.
In addition the following study gives ample evidence that Aromatase Inhibitors (Letrozole, Arimidex, etc...) will also combat progesterone:
J Steroid Biochem Mol Biol. 2005 May;95(1-5):83-9. Related Articles, Links
Aromatase inhibitors: cellular and molecular effects.
Miller WR, Anderson TJ, White S, Larionov A, Murray J, Evans D, Krause A, Dixon JM.
Breast Unit, Western General Hospital, Edinburgh, Scotland, UK.
[email protected]
Marked cellular and molecular changes may occur in breast cancers following treatment of postmenopausal breast cancer patients with aromatase inhibitors. Neoadjuvant protocols, in which treatment is given with the primary tumour still within the breast, are particularly illuminating. In Edinburgh, we have shown that 3 months treatment with either anastrozole, exemestane or letrozole produces pathological responses in the majority of oestrogen receptor (ER)-rich tumours (39/59) as manifested by reduced cellularity/increased fibrosis. Changes in histological grading may also take place, most notably a reduction in mitotic figures. This probably reflects an influence on proliferation as most tumours (82%) show a marked decrease in the proliferation marker, Ki67. These effects are generally more dramatic than seen with tamoxifen given in the same setting. Differences between aromatase inhibitors and tamoxifen are also apparent in changes in steroid hormone expression.
Thus, immuno-staining for progesterone receptor (PgR) is reduced in almost all cases by aromatase inhibitors, becoming undetectable in many. This contrasts with effects of tamoxifen in which the most common change on PgR is to increase expression. Changes in proliferation occur rapidly following the onset of exposure to aromatase inhibitors. Thus, neoadjuvant studies with letrozole in which tumour was sampled before and after 14 days and 3 months treatment show that decreased expression of Ki67 occur at 14 days and, in many cases, the effect is greater at 14 days than 3 months. These early changes precede evidence of clinical response but do not predict for it. However, this study design has allowed RNA analysis of sequential biopsies taken during the neoadjuvant therapy. Based on clustering techniques, it has been possible to subdivide tumours into groups showing distinct patterns of molecular changes. These changes in tumour gene expression may allow definition of tumour cohorts with differing sensitivity to aromatase inhibitors and permit early recognition of response and resistance.
PMID: 16002280 [PubMed - indexed for MEDLINE]
J Steroid Biochem Mol Biol. 2003 Sep;86(3-5):461-7.
Use of letrozole as a chemopreventive agent in aromatase overexpressing transgenic mice.
Luthra R, Kirma N, Jones J, Tekmal RR.
Department of Gynecology and Obstetrics, Emory University School of Medicine, 4217 Woodruff Memorial Building, Atlanta, GA 30322-4710, USA.
Our recent studies have shown that overexpression of aromatase results in increased tissue estrogenic activity and induction of hyperplastic and dysplastic lesions in mammary glands, and gynecomastia and testicular cancer in male aromatase transgenic mice. Our studies also have shown that aromatase overexpression-induced changes in mammary glands can be abrogated with very low concentrations of letrozole, an aromatase inhibitor without any effect on normal physiology. In the present study, we have examined the effect of prior low dose letrozole treatment on pregnancy and lactation. We have also investigated the effect of low dose letrozole treatment on subsequent mammary growth and biochemical changes in these animals. There was no change in the litter size, birth weight and no visible birth defects in letrozole-treated animals. Although, there was an insignificant increase in mammary growth in aged animals after 6 weeks of letrozole treatment,
the levels of expression of estrogen receptor, progesterone receptor and genes involved in cell cycle and cell proliferation remained low compared to control untreated animals. These observations indicate that aromatase inhibitors such as letrozole can be used as chemopreventive agents without effecting normal physiology in aromatase transgenic mice.
Cancer Invest. 2002;20 Suppl 2:15-21.
Anti-tumor effects of letrozole.
Miller WR, Anderson TJ, Dixon JM.
Breast Unit Research Group, University of Edinburgh, Western General Hospital, Edinburgh, EH4 2XU, UK.
[email protected]
The use of drugs, which inhibit estrogen biosynthesis, is an attractive treatment for postmenopausal women with hormone-dependent breast cancer. Estrogen deprivation is most specifically achieved using inhibitors which block the last stage in the biosynthetic sequence, i.e., the conversion of androgens to estrogens by the aromatase enzyme. Recently, a new generation of aromatase inhibitors has been developed. Among these, letrozole (Femara) appears to be the most potent. When given orally in milligram amounts per day to postmenopausal women, the drug almost totally inhibits peripheral aromatase and causes a marked reduction in circulating estrogens to levels that are often undetectable in conventional assays. Similarly, neoadjuvant studies demonstrate that letrozole substantially inhibits aromatase activity in both malignant and nonmalignant breast tissues, and markedly suppresses endogenous estrogens within the breast cancers.
These studies also illustrate anti-estrogenic and anti-proliferative effects of letrozole in estrogen receptor (ER)-rich tumors. Thus, tumor expression of progesterone receptors and the cell-cycle marker Ki67 is significantly and consistently reduced with treatment. Additionally, clear pathological responses as evidenced by decreased cellularity and increased fibrosis are seen in the majority of cases. These results translated into clinical benefit in a series of 24 breast cancers treated neoadjuvantly with letrozole (either 2.5 or 10 mg): tumor volume reductions > 25% were observed in 23 women, and > 50% reductions in 18 patients. Pathological and clinical effects are seen much more consistently than with tamoxifen. Thus, in a multicenter randomized trial of letrozole vs. tamoxifen (PE 024), clinical study outcomes were superior for letrozole in comparison with tamoxifen with regard to overall tumor response and an increase in the proportion of patients treated by breast conserving surgery. Letrozole has also been used in advanced breast cancer, both as second-line hormone treatment following tamoxifen failure, and more recently as first-line therapy. Trials of second-line treatment in which letrozole has been compared with either older aromatase inhibitors or progestins have shown equivalent or superior clinical activity and improved tolerability favoring letrozole. In first-line comparison with tamoxifen in metastatic disease, a phase III trial of over 900 postmenopausal women showed letrozole to be significantly better than tamoxifen in terms of overall tumor response rates, clinical benefit, and time to treatment failure. In summary, letrozole is an exceptionally potent and specific endocrine agent. In patients with ER-rich tumors, high rates of pathological and clinical response have been documented, and large phase III trials against established treatments such as tamoxifen and progestin suggest superior (or at least equivalent) clinical efficacy. Letrozole is a drug of immense potential and in the future is likely to occupy a central role in the management of postmenopausal women with hormone-dependent breast cancer.
.gif "IP Gear")
