The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research<sup>*</sup>

Neumann, F.

doi:10.1055/s-0029-1211261

Cited by 83 publications

(26 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, this is unlikely because, in addition to the suppression of the release of hypothalamic GnRH by a negative feedback and subsequent androgen secretion (progestin action), CA blocks the androgen receptors (Neumann & Töpert 1986, Neumann 1994.…”

Section: Discussionmentioning

confidence: 99%

Role of testosterone and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex: a model for polygynous wild bovids

Santiago-Moreno¹,

Gómez-Brunet²,

Toledano-Dı́az³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

This work examines the effect of testosterone secretion and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex (Capra pyrenaica), here used as a model for polygynous wild bovids. The hypothesis that high levels of testosterone provide an endocrine signal that inhibits horn growth in autumn was tested by assessing the effect of cyproterone acetate (CA), an anti-androgen, administered in October -coinciding with the period of natural increases in plasma testosterone concentrations -under different photoperiodic conditions (natural photoperiod and artificial long days). The persistence of horn growth during autumn in all ibexes held under the long-day photoperiodic conditions clearly shows that horn growth regulation in the mating season is primarily modulated by day length and not by a fall in testosterone concentration. A retrospectively designed second experiment involving testosterone propionate (TP) administration in April (when horns are growing) was then undertaken to confirm that high levels of testosterone do not inhibit horn growth. Overall, the results strongly suggest that the rise in testosterone secretion during the autumn mating season does not act as an endocrine signal for the arrest of horn growth, although the rate of horn growth before the mating season may be related to springtime testosterone levels. A direct relationship was seen between the rate of horn growth and the incidence of sperm abnormalities. Neither CA treatment in October nor TP administration in April affected the studied sperm variables. By contrast, CA treatment plus artificial long days in autumn had a negative effect on sperm motility and sperm morphology.

show abstract

Section: Discussionmentioning

confidence: 99%

Role of testosterone and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex: a model for polygynous wild bovids

Santiago-Moreno¹,

Gómez-Brunet²,

Toledano-Dı́az³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…This study included two types of aryl piperazines, compounds having an aryl group directly attached to N 4 -position (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) and compounds in which the N 4 -aryl substituent was separated by a one-carbon linker (a methylene or a carbonyl group, 20-32). The aryl substituents at N 1 -position were 3-chlorophenyl, 3-(trifluoromethyl)phenyl, 4-fluorophenyl, 2-pyridyl, and 2-pyrimidyl, while the aryl group at N 4 -position was either nitro substituted or nitro and trifluoromethyl disubstituted.…”

Section: Resultsmentioning

confidence: 99%

“…Aryl/heteroaryl piperazines (1)(2)(3)(4)(5) were treated with appropriate aryl halide to provide diaryl piperazines (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) whereas the reaction of 1-5 with suitable aroyl chloride furnished 1-aryl-4-aroylpiperazines (20)(21)(22)(23)(24)(25)(26)(27)(28). Similarly, appropriate benzyl chlorides gave 1-aryl-4-arylmethylpiperazines (29)(30)(31)(32).…”

Section: Chemistrymentioning

confidence: 99%

Arylpiperazines for Management of Benign Prostatic Hyperplasia: Design, Synthesis, Quantitative Structure−Activity Relationships, and Pharmacokinetic Studies

Sarswat

Kumar

et al. 2010

J. Med. Chem.

View full text Add to dashboard Cite

A series of 27 aryl/heteroaryl/aralkyl/aroyl piperazines were synthesized, and most of these compounds reduced prostate weight of mature rats by 15-47%. Three compounds, 10, 12, and 18, had better activity profile (reduced prostate weight by 47%, 43%, and 39%, respectively) than the standard drug flutamide (24% reduction). QSAR suggested structures with more cyclic and branched moieties, increased topological separation of O and N therein, and reduced solvation connectivity index for better activity. Pharmacokinetic study with compound 10 at an oral dose of 10.0 mg/kg indicated good absorption, negligible extrahepatic elimination, and rapid distribution to the target organ (prostate) but restricted entry through the blood-brain barrier. A 10-fold decrease in PSA and 15-fold increase in ER-β gene expressions of human prostate cancer cells (LNCaP) by compound 10 in vitro indicated AR and ER-β mediated actions. The findings may stimulate further explorations of identified lead for the management of benign prostatic hyperplasia.

show abstract

“…Unlike the combined oral contraceptives (COCs) commonly used to treat hyperandrogenic symptoms, cyproterone acetate (CPA) 2 mg, combined with ethinylestradiol (EE) 35 lg, is indicated for the treatment of moderate to severe acne related to androgen-sensitivity (with or without seborrhea) and/or hirsutism, in women of reproductive age [9]. CPA is a steroidal antiandrogen: it competitively inhibits the binding of both testosterone and its conversion product, 5-a-dihydrotestosterone (DHT) to the androgen receptor; it reduces testosterone and androstenedione production in the ovary; it blocks the conversion of testosterone to DHT by inhibiting the 5-a-reductase [10][11][12][13][14][15][16].…”

Section: Principles Of Pharmacologic Treatmentmentioning

confidence: 99%

The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms – a review

Bitzer

Römer

Filho³

2017

The European Journal of Contraception & Reproductive Health

View full text Add to dashboard Cite

Introduction: Hyperandrogenism affects approximately 10-20% of women of reproductive age. Hyperandrogenic skin symptoms such as hirsutism, acne, seborrhea and alopecia are associated with significant quality of life and psychological impairment. Women with abnormalities in androgen metabolism may have accompanying anovulation and/or polycystic ovary syndrome (PCOS), both of which have reproductive and metabolic implications if left untreated. Cyproterone acetate (CPA), combined with ethinylestradiol (EE), is indicated for the treatment of moderate to severe acne related to androgen-sensitivity (with or without seborrhea) and/or hirsutism, in women of reproductive age. Objective: To review the data on the efficacy and safety of CPA 2 mg/EE 35 lg for the treatment of hyperandrogenic skin symptoms in women. Methods: A non-systematic narrative review based on a literature search of the PubMed database. Results: Seventy-eight studies were identified. The majority of sufficiently powered studies show a high efficacy of CPA 2 mg/EE 35 lg in the treatment of severe acne and hirsutism. Studies show that therapeutic response in women with hirsutism requires a long-term approach and that hyperandrogenic skin symptoms in patients with PCOS are efficiently treated. Additional benefits include cycle control and, in some women, improvement in mood and perception of body image. Safety and tolerability data are summarized by the pharmacovigilance risk assessment committee (PRAC) of the European Medicine's Agency's (EMA). Conclusions: This review provides a comprehensive overview about the efficacy of CPA 2 mg/EE 35 lg in the treatment of hyperandrogenic skin symptoms, thus allowing both health care professionals and women to balance the risks and benefits of treatment based on evidence.

show abstract

The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research^*

Cited by 83 publications

References 56 publications

Role of testosterone and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex: a model for polygynous wild bovids

Role of testosterone and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex: a model for polygynous wild bovids

Arylpiperazines for Management of Benign Prostatic Hyperplasia: Design, Synthesis, Quantitative Structure−Activity Relationships, and Pharmacokinetic Studies

The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms – a review

Contact Info

Product

Resources

About

The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research*

Cited by 83 publications

References 56 publications

Role of testosterone and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex: a model for polygynous wild bovids

Role of testosterone and photoperiod on seasonal changes in horn growth and sperm variables in the Iberian ibex: a model for polygynous wild bovids

Arylpiperazines for Management of Benign Prostatic Hyperplasia: Design, Synthesis, Quantitative Structure−Activity Relationships, and Pharmacokinetic Studies

The use of cyproterone acetate/ethinyl estradiol in hyperandrogenic skin symptoms – a review

Contact Info

Product

Resources

About

The antiandrogen cyproterone acetate: discovery, chemistry, basic pharmacology, clinical use and tool in basic research^*