Search PubMed⌕ Search
Home/Archive/PubMed

PubMed · 9829156

Dienogest.

R H Foster·M I Wilde
View original source ↗Export metadata ↓

Abstract

The progestogen dienogest exhibits highly selective binding to the progesterone receptor. It has high progestational and significant antiandrogenic activity, but only moderate antigonadotrophic activity. Dienogest inhibits ovulation, produces secretory transformation of the endometrium and has antiproliferative effects. Oral dienogest 2 mg/day plus ethinylestradiol 30 micrograms/day provides effective contraception (Pearl Index approximately 0.2). Cycle stability is good during long term use of this combination; irregular vaginal bleeding was evident in 6% of women after 12 months' use. Androgenic symptoms (including hirsutism, seborrhoea, alopecia, acne vulgaris and hair and skin greasiness) improved in women treated with dienogest plus ethinylestradiol. The adverse events associated with dienogest are typical of those expected of a progestogen. The drug does not produce androgenic adverse effects and has little clinically significant effect on metabolic, lipid and haemostatic parameters.

Explore related subjects

Androgen AntagonistsAnimalsClinical Trials as TopicContraceptives, OralEthinyl EstradiolFemaleHumansNandroloneProgestinsJournal ArticleReview

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

R H Foster, M I Wilde. 1998. Dienogest.. https://doi.org/10.2165/00003495-199856050-00007

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2004

Prostate cancer cells generated during intermittent androgen ablation acquire a growth advantage and exhibit changes in epidermal growth factor receptor expression.

BACKGROUND: Intermittent androgen ablation is a palliative treatment option for advanced prostate cancer which is associated with less side effects, improved quality of life of patients, and reduced costs. Regulation of growth and survival of prostate cancer cells during intermittent androgen withdrawal has not been studied in appropriate models yet. METHODS: Two cycles of androgen withdrawal and supplementation were performed in human prostate cancer cells LNCaP in vitro. Proliferation of prostate cancer cell sublines established after intermittent androgen withdrawal was assessed in the absence or presence of epidermal growth factor (EGF) by protein determination. Cell cycle was analyzed with a flow cytometer. EGF was measured in the supernatants of LNCaP sublines with a commercial ELISA. EGF receptor mRNA and protein were determined by real-time PCR and Western blot, respectively. RESULTS: Basal proliferation rate of all newly generated LNCaP sublines increased over that of the parental LNCaP cell line. The highest stimulation of proliferation by exogenous EGF was observed in parental LNCaP cells. In each LNCaP derivative established during intermittent androgen withdrawal, the percentage of cells in the S phase of cell cycle was higher than that in parental LNCaP cells. EGF levels did not increase during intermittent androgen ablation. The expression of EGF receptor protein decreased following each cycle of androgen ablation and increased subsequently after androgen supplementation. EGF receptor (EGFR) mRNA was regulated in a similar manner in LNCaP derivatives established during the second cycle of intermittent withdrawal. CONCLUSIONS: Changes in the expression of the EGF receptor occur during intermittent androgen ablation but they cannot be solely responsible for increased basal proliferation. Alternatively, other ligands and receptors of the EGF system may become overexpressed during prolonged withdrawal and supplementation of androgenic hormones in prostate cancer therapy.

Androgen Antagonists↗
PubMed2004

Differential modulation of androgen receptor transcriptional activity by the nuclear receptor co-repressor (N-CoR).

Antiandrogens are widely used agents in the treatment of prostate cancer, as inhibitors of AR (androgen receptor) action. Although the precise mechanism of antiandrogen action is not yet elucidated, recent studies indicate the involvement of nuclear receptor co-repressors. In the present study, the regulation of AR transcriptional activity by N-CoR (nuclear receptor co-repressor), in the presence of different ligands, has been investigated. Increasing levels of N-CoR differentially affected the transcriptional activity of AR occupied with either agonistic or antagonistic ligands. Small amounts of co-transfected N-CoR repressed CPA (cyproterone acetate)- and mifepristone (RU486)-mediated AR activity, but did not affect agonist (R1881)-induced AR activity. Larger amounts of co-transfected N-CoR repressed AR activity for all ligands, and converted the partial agonists CPA and RU486 into strong AR antagonists. In the presence of the agonist R1881, co-expression of the p160 co-activator TIF2 (transcriptional intermediary factor 2) relieved N-CoR repression up to control levels. However, in the presence of RU486 and CPA, TIF2 did not functionally compete with N-CoR, suggesting that antagonist-bound AR has a preference for N-CoR. The AR mutation T877A (Thr877-->Ala), which is frequently found in prostate cancer and affects the ligand-induced conformational change of the AR, considerably reduced the repressive action of N-CoR. The agonistic activities of CPA- and hydroxyflutamide-occupied T877A-AR were hardly affected by N-CoR, whereas TIF2 strongly enhanced their activities. These results indicate that lack of N-CoR action allows these antiandrogens to act as strong agonists on the mutant AR.

Androgen Antagonists↗
PubMed2004

Effects of a model androgen (methyl testosterone) and a model anti-androgen (cyproterone acetate) on reproductive endocrine endpoints in a short-term adult mummichog (Fundulus heteroclitus) bioassay.

A short-term gonadal recrudescence bioassay using the mummichog (Fundulus heteroclitus) was employed to examine the consequences of environmentally relevant and pharmacological exposures (1-1000 ng/l) of the androgen, 17alpha-methyl testosterone (MT), and the anti-androgen, cyproterone acetate (CA), on reproductive endocrine endpoints. Recrudescing male (GSI = approx. 2%) and female (GSI = approx. 10%) fish were exposed to graded concentrations of MT and CA for 7 or 14 days. In the first experiment (7-day exposure), MT concentrations of 250 or 1000 ng/l decreased circulating testosterone (T) and estradiol (E(2)) in female fish, and 11-ketotestosterone (11-KT) in male fish. Plasma T, 11-KT and E(2) were decreased following CA exposure (250 and 1000 ng/l). Gonadal steroid biosynthetic capacity was also inhibited in both sexes after exposure to MT or CA, as evidenced by decreased in vitro production of T and E(2). In experiment 2 (14-day exposure), exposures to lower MT and CA concentrations (1, 10 and 100 ng/l) resulted in decreased plasma T, with females showing greater sensitivity than males. Both 11-KT and E(2) were significantly reduced beginning at 10 ng/l MT. In vitro gonadal T production was impaired at 100 ng/l MT in both males and females while 1 ng/l CA caused a significant decrease in female fish. In experiment 2, in vitro E(2) production was decreased in females at all concentrations of MT and CA, while only 100 ng/l reduced 11-KT synthesis in males. Plasma vitellogenin (Vtg) was reduced in females exposed to 1000 ng/l (experiment 1) and 100 ng/l (experiment 2) MT, while CA did not alter plasma Vtg at any concentration. This bioassay has the potential to be used to assess the possible consequences in estuarine fish of exposure to environmental anti/androgens.

Androgen Antagonists↗