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Progestogen use and breast cancer
Published in Barry G. Wren, Progress in the Management of the Menopause, 2020
In another population of premenopausal French women suffering from benign breast diseases, we followed 1150 patients for 10 years and longer comparing women who received high doses of 19-norsteroids for 15 days per cycle, to those who did not. The relative risk of breast cancer in the progestin users was 0.48 (CI 0.26–0.93) with a significant linear trend for a decrease in the RR of breast cancer with duration of use. Although the population was not of postmenopausal but younger women, these results suggest at least that high doses of 19-norsteroid progestins did not increase the risk of breast cancer.
Radiotracer Interactions with Sex Steroid Hormone Receptor Proteins (Receptor Mapping)
Published in Lelio G. Colombetti, Principles of Radiopharmacology, 1979
Raymond E. Counsell, William H. Klausmeier
The deletion or modification of functionalities produce variable effects. Norsteroids lacking a methyl group at C-10 still prove to be moderately androgenic (Compounds 129 and 130). Indeed, several such norsteroids, substituted at the 7α and/or 17α positions, prove to be even more androgenic than DHT (Compounds 181 and 191). Modification of functionalities in the A ring generally lead to reduced, but not extinguished androgenicity. Reduction of the carbonyl group at the 3 carbon to a hydroxyl group of either testosterone or 5α-DHT produces compounds of moderate androgenicity (Compound 140). This may, in part, be due to metabolism to more active 3-ketosteroids.93 While the presence of a carbon-oxygen bond at the 3 carbon is important for high androgenicity, it is not essential for the exhibition of low to moderate androgenicity or receptor affinity-provided that the stereochemistry and key functionalities in the rest of the molecule, such as the 17β alcohol, remain intact (Compounds 133 and 139). Numerous other 5α-androstan-17β-alcohols possessing various A-ring functionalities, but lacking carbon-oxygen bonds at the 3 carbon have also proven to be fairly biologically active.92
A cohort study of the efficacy of the dienogest and the gonadotropin-releasing hormone agonist in women with adenomyosis and dysmenorrhea
Published in Gynecological Endocrinology, 2022
Miaomiao Ji, Ming Yuan, Xue Jiao, Qiuju Li, Yufei Huang, Jing Li, Guoyun Wang
Dienogest (DNG), a progestational 19-norsteroid derivative, has strong progestational effects and increased bioavailability due to its high selectivity to the progesterone receptor [4]. Its administration results in mild hypoestrogenic effects as well as antiovulatory and antiproliferative activities on endometrial cells [5]. Daily intake of 2 mg of dienogest has been reported as a treatment for symptomatic adenomyosis in Japan. DNG has long been prescribed to reduce adenomyosis-related dysmenorrhea. DNG was marketed in China in 2018; however, experience involving the treatment of adenomyosis with DNG remains limited. To study the effectiveness and safety of dienogest and GnRH-a for symptomatic adenomyosis, we conducted this prospective cohort research in premenopausal patients.
Progesterone, progestins and the breast in menopause treatment
Published in Climacteric, 2018
Progestins such as progesterone are not selective for PR as ligand. They are able to bind and behave as agonist or antagonist on androgen receptors (AR), mineralocorticoid receptors (MR), and glucocorticoid receptors (GR); furthermore, several norsteroids are partially metabolized in estrogenic derivatives with low affinity for the ER. Breast tissue contains large amounts of GR, AR and MR. Interestingly, PR and GR are closely related and bind to the same response element in the promoters and enhancers of target genes. We have shown that the active form of GR, phosphorylated on serine 211, was abundant in luminal cells and that glucocorticoids were proliferative and anti-apoptotic in normal breast cells44. MPA is a strong glucocorticoid agonist as well as an AR agonist. Progesterone is anti-androgenic and has only a mild activity on GR, probably without any clinical significance45. We have reported that MPA and progesterone have different properties in normal human breast and breast cancer cells due to the glucocorticoid potency of MPA44. The role of the androgenic or anti-androgenic potencies is also likely to be involved in driving different levels of risk. According to the phenotypes of breast cancer, GR, AR and MR can be involved, with an unpredictable effect. Publications on GR report an opposite relation between survival and GR expression in ER-positive and ER-negative breast cancers46. In ER-negative breast cancers, high GR expression was associated with a poor prognosis47. However, these studies looked at the expression of total GR. We have observed that the expression of total GR does not correspond to the activated form of the receptor48, suggesting that more data are needed on the role of glucocorticoids in breast cancer. In addition, the impact of GR and AR may vary according to the phenotype and the grade of breast cancer. We also reported a loss of expression of the GR active form only in triple-negative cancers from BRCA1 mutation carriers48. AR is also associated with different types of breast cancer and possibly with a worse prognosis, so that trials for an evaluation of benefit of antiandrogen treatment are ongoing, notably in triple-negative cancers49–51. In addition to the binding to various steroid receptors, the metabolism of progestin and progesterone could also modify the potencies through different half-lives and bioavailabilities45.