Preliminary report of patients with meningiomas exposed to Cyproterone Acetate, Nomegestrol Acetate and Chlormadinone Acetate – Monocentric ongoing study on progestin related meningiomas

Abstract. Nomegestrol acetate, like other synthetic progestins such as medroxyprogesterone acetate (MPA), chlormadinone acetate, megestrol acetate and cyproterone acetate, is able to modify the physiological actions of androgens. In the present study, the effects of nomegestrol acetate and other antiandrogens on the binding of androgen to the androgen receptor (AR) and on the 'activation' of this receptor were investigated, using rat ventral prostate as target model. Relative binding affinities (RBA) for AR were first estimated in vitro with respect to [3H]testosterone for a series of structurally-related compounds. The values obtained ranged as follows: dihydrotestosterone (DHT) » megestrol acetate ≥ testosterone (T) > nomegestrol acetate > 19-nor progesterone (19NP) > progesterone (P). An assay was established, using two different incubation times (3 h and 24 h) to further investigate relationships between binding affinity and androgenic, or antiandrogenic, activity. The following order (as %) was obtained for progestins as against [3H]mibolerone (DMNT): 1) DMNT (100) » acetate (42) > megestrol acetate (29) > chlormadinone acetate (9) > MPA (8) > cyproterone acetate (6) after 3 h and 2) DMNT (100) » MPA (53) » nomegestrol acetate (19) > megestrol acetate (12) > chlormadinone acetate (14) and cyproterone acetate (8) after 24 h. Since the RBA of nomegestrol acetate declined with time, these results indicate that this substance may act like an antiandrogen rather than an androgen, while the contrary prevails concerning MPA. The effects of these progestins, administered either alone or in combination with DHT to the animals, on the location (nuclear or cytosolic) of AR were also analyzed. DHT (0.05 or 4 mg/kg) produced maximal nuclear location of AR. Of the progestins tested, only MPA and norethisterone acetate reproduced this effect, while other steroids were ineffective. Furthermore, cyproterone acetate, megestrol acetate and nomegestrol acetate were able to inhibit to a large extent the DHT-elicited effect. The evidence from these studies suggests that the new compound nomegestrol acetate may oppose the actions of androgens on ventral prostate by directly interacting with the androgen receptor.

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DNA-damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver

Carcinogenesis ◽

10.1093/carcin/16.7.1483 ◽

1995 ◽

Vol 16 (7) ◽

pp. 1483-1487 ◽

Cited By ~ 16

Author(s):

J. Topinka ◽

B. Binkova ◽

H.K. Zhu ◽

U. Andrae ◽

I. Neumann ◽

...

Keyword(s):

Rat Liver ◽

Cyproterone Acetate ◽

Megestrol Acetate ◽

Chlormadinone Acetate

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LHRH agonist ICI 118.630 (Zoladex depot) (Z) versus Z plus Cyproterone Acetate (CPA) in advanced prostatic cancer. Preliminary report

European Journal of Cancer and Clinical Oncology ◽

10.1016/0277-5379(86)90284-1 ◽

1986 ◽

Vol 22 (6) ◽

pp. 744

Author(s):

V. Dongiovanni ◽

O. Bertetto ◽

M. Clerico ◽

A. Calciati

Keyword(s):

Cyproterone Acetate ◽

Prostatic Cancer ◽

Preliminary Report ◽

Lhrh Agonist ◽

Advanced Prostatic Cancer

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Nomegestrol Acetate or Chlormadinone Acetate Progestative Treatment in Women: Meningioma Behavior at Treatment Discontinuation

10.21203/rs.3.rs-517160/v1 ◽

2021 ◽

Author(s):

Simona Mihaela Florea ◽

Sebastien Boissonneau ◽

Thibault Passeri ◽

Anne Laure Bernat ◽

Emmanuel Mandonnet ◽

...

Keyword(s):

Treatment Discontinuation ◽

Intracranial Meningioma ◽

Close Monitoring ◽

Chlormadinone Acetate ◽

Multiple Meningiomas ◽

Urgent Surgery ◽

Nomegestrol Acetate ◽

Multiple Meningioma ◽

Stopping Treatment

Abstract Background: Associations between progestins and meningiomas is now well established. While the link between cyproterone acetate (CA) and meningioma was thoroughly studied, there is far less available data regarding the link between chlormadinone acetate (CHA) or nomegestrol acetate (NA) and risk of intracranial meningiomaMethods: We are presenting a series of 28 patients diagnosed with single or multiple meningiomas while treated with CHA-NA, in which the clinical and radiological course were analyzed after treatment discontinuation.Results: 28 women, with a mean age of 56 years old, were diagnosed with one or multiple meningioma while being treated with either CHA or NA. After stopping treatment, 89.3% showed either tumor shrinkage or tumor stabilization on follow-up MRIs. Multiple meningiomas were more likely observed in patients with long periods of treatment (>10 years, p 0.03) and seem to have a better clinical course (p 0.01). Most of the lesions were located on the skull base (55.4%). Four patients with multiple meningiomas showed discordant tumors evolution, with some tumors growing while others were decreasing. Most of the growing meningiomas were either convexity or midline lesions and more posteriorly located. Conclusion: Our study demonstrated a significant percentage of tumor diminution or stabilization after NA and CHA discontinuation. Therefore, treatment discontinuation with close monitoring should be the first measure taken if urgent surgery is not indicated. However, our results seem to be less encouraging than previously described in patients treated by CA, with more patients showing tumor growth despite treatment discontinuation. Further studies are needed to differentiate the effect of the different progestins treatment on meningiomas.

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Effect of oral contraceptives containing estradiol and nomegestrol acetate or ethinyl-estradiol and chlormadinone acetate on primary dysmenorrhea

Gynecological Endocrinology ◽

10.3109/09513590.2015.1063118 ◽

2015 ◽

Vol 31 (10) ◽

pp. 774-778 ◽

Cited By ~ 6

Author(s):

Giovanni Grandi ◽

Antonella Napolitano ◽

Anjeza Xholli ◽

Alessandra Tirelli ◽

Costantino Di Carlo ◽

...

Keyword(s):

Oral Contraceptives ◽

Ethinyl Estradiol ◽

Primary Dysmenorrhea ◽

Chlormadinone Acetate ◽

Nomegestrol Acetate

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Antigonadotropic progestogens as contraceptive agents in women with contraindication to combined pill

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci.2010.062 ◽

2010 ◽

Vol 3 (3) ◽

Author(s):

Lorraine Maitrot-Mantelet ◽

Anahid Agopian ◽

Anne Gompel

Keyword(s):

Side Effects ◽

Cyproterone Acetate ◽

Steroid Receptors ◽

Hormonal Contraception ◽

Systemic Lupus Erythematous ◽

Vascular Risk ◽

Systemic Lupus ◽

Chlormadinone Acetate ◽

Contraceptive Agents ◽

Current Experience

AbstractSynthetic progestogens belong to different pharmacological classes and are mixed steroids. They display different properties due to their various affinities to the different steroid receptors. In addition, the dosage used can modify their side effects. Normethyltestosterone used at minimal doses, also called progestogen only pill (POP), constitute the standard recommended hormonal contraception for women with vascular and metabolic contraindications to combined pill (COC). However, POP efficacy and gynecological tolerance are limited. We have developed for more than 20 years in France the use of two pregnane derivatives as contraceptive agents in women with contraindication to COC. Chlormadinone acetate and cyproterone acetate have different antigonadotropic potencies but remain neutral on vascular risk. We have analyzed the efficacy, vascular and gynecological tolerances in 187 women with systemic lupus erythematous with or without antiphospholipids. Venous thrombosis and arterial events rates were lower than those reported in the literature. The current experience in women with thrombophilia is similar as reported in a series of 150 patients. In addition, we have also used antigonadotropic progestins in women with hereditary angioedema (HAE) types I, II or III. HAE symptoms can be induced or worsened by COC. We could demonstrate a significant improvement of the symptoms in most women with HAE under antigonadotropic progestins. Gynecological and general tolerances were satisfactory. In conclusion, antigonadotropic progestins could have clinical positive benefits as contraceptive agents in women with contraindication to COC.

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Intralesional Cidofovir for Recurrent Laryngeal Papillomas: Preliminary Report

Ear Nose & Throat Journal ◽

10.1177/014556130007900407 ◽

2000 ◽

Vol 79 (4) ◽

pp. 236-240 ◽

Cited By ~ 26

Author(s):

William R. Wilson ◽

Robert Hashemiyoon ◽

Andrew Hawrych

Keyword(s):

Preliminary Report ◽

Antiviral Drug ◽

Ongoing Study ◽

Safety And Efficacy ◽

Intralesional Injections ◽

New Treatment ◽

A Minor

This is a preliminary report of an ongoing study to test the efficacy of intralesional injections of the antiviral drug cidofovir in adults with recurrent laryngeal papillomas in whom multiple other treatments have previously failed. This study has been designed to include 10 to 20 patients, a number sufficient to either prove or disprove the safety and efficacy of this agent. This report conveys information on the first three patients enrolled in the trial. Each patient received an overall dose of 5 to 10 ml of cidofovir, at a concentration of 4.17 mg/ml, intralesionally at 2- to 4-week intervals. The approximate volume injected into each wart was 0.2 to 0.5 ml. Biopsies of the lesion sites were obtained at the initiation and completion of therapy. No other treatment was given. Resolution of lesions was monitored by videolaryngoscopy and still photography 1 to 2 weeks after each treatment. In time, the lesions resolved in all three patients, although all three later experienced a minor recurrence. We conclude that intralesional cidofovir appears to be a promising new treatment for controlling—and perhaps at higher dosages curing—refractory laryngeal papillomas, while causing little or no injury to laryngeal structures.

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Formation of DNA-adducts by selected sex steroids in rat liver

Human & Experimental Toxicology ◽

10.1177/096032719601500702 ◽

1996 ◽

Vol 15 (7) ◽

pp. 556-562 ◽

Cited By ~ 13

Author(s):

W. Feser ◽

RS Kerdar H Blode ◽

R. Reimann

Keyword(s):

Rat Liver ◽

Dna Adducts ◽

Sex Steroids ◽

Cyproterone Acetate ◽

Adduct Formation ◽

Dna Adduct ◽

Male Rats ◽

Female Rat ◽

Chlormadinone Acetate

1 We are reporting investigations into the potential of the steroid hormones chlormadinone acetate (CMA), cyproterone acetate (CPA), ethinylestradiol (EE2) gestodene (GEST), megestrol acetate (MGA), norethis terone acetate (NET-Ac), estradiol (E 2), and progester one (P) to form DNA-adducts in rat liver in vivo. 2 Compound-related DNA-adduct spots were detected in male and female rat liver following CMA, CPA, and MGA using the 32P-postlabeling-technique. Substance- specific DNA-adducts were also observed in male rats after administration of E2. The other compounds showed no DNA-adduct formation. After treatment with CMA, CPA or MGA, the relative adduct labeling (RAL) differed sex- and substance-specifically.

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