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Systemic Diseases and the Skin
Published in Ayşe Serap Karadağ, Lawrence Charles Parish, Jordan V. Wang, Roxburgh's Common Skin Diseases, 2022
Jana Kazandjieva, Razvigor Darlenski, Nikolai Tsankov
Management: It takes up to 6 months before a significant difference in hair growth is noticed. Drugs such as oral contraceptives, androgen receptor blockers, 5-alpha reductase inhibitors, and systemic glucocorticoids are indicated for treatment when hyperandrogenism is confirmed by various laboratory tests. Antiandrogens are indicated for moderate to severe hirsutism, with spironolactone being the first-line antiandrogen and finasteride and cyproterone acetate being second-line antiandrogens. Due to its risk for hepatotoxicity, flutamide is not considered a first-line therapy. Gonadotropin-releasing hormone analogs and glucocorticoids are only recommended in specific circumstances.
Summary of Hair Diseases: Cicatricial and Non-Cicatricial
Published in Rubina Alves, Ramon Grimalt, Techniques in the Evaluation and Management of Hair Diseases, 2021
Aurora Alessandrini, Bianca Maria Piraccini, Michela Starace
CPA acts by interfering with the binding of 5-alpha DHT to the androgen receptor and by inhibiting the secretion of FSH and LH, as the result of its progestinic action. Contemporary administration of estrogen (ethynyl estradiol or oral contraceptives) is mandatory to enhance the anti-androgen activity. Spironolactone can arrest hair loss progression with a favorable long-term safety profile, too [20–22]. Flutamide is a non-steroidal selective antiandrogen that inhibits the binding of androgens to their receptors and it may be a treatment option in patients with normal androgen levels, even if a standardized dosage has not been established [23, 24]. The risk of hepatotoxicity due to this drug is well-known, but it's dose-dependent rather than idiosyncratic; therefore, with low doses this risk completely disappears without altering its potent anti-androgen activity [24]. Other options for the treatment are: platelet-rich plasma (PRP) [25, 26], low-level laser (light) therapy [27], and surgery [28, 29].
Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Flutamide is approved in the UK for use in advanced prostate cancer, and as a monotherapy in metastatic prostate cancer refractory to gonadorelin analog therapy. It can also be used to inhibit the tumor “flare” that can occur after a patient is initiated on a GnRH antagonist. A combination of flutamide with an estrogen such as ethinylestradiol sulfonate has been used as a form of combined androgen blockade, and as an alternative to the combination of flutamide with surgical or medical castration. It is worth noting that most advanced prostate cancer patients eventually become resistant to bicalutamide therapy, although the mechanism is not well established. The agent is also used in women for the treatment of medical conditions involving high androgen levels such as polycystic ovary syndrome, excessive hair growth, and acne.
An evaluation of the available pharmacotherapy for the treatment of hirsutism
Published in Expert Opinion on Pharmacotherapy, 2023
Leila Asfour, Ahmed Kazmi, Rodney Sinclair
Flutamide works by blocking the androgen receptor. The most common dose used in literature for hirsutism was 500 mg, but it has been demonstrated that 250 mg is equally effective. Several data suggest low-dose flutamide is also effective in treating hirsutism (62.5 mg-250 mg) [34]. Flutamide has been associated with liver failure and death [49]. However, this has not been the case with lower doses of flutamide. In a long term follow-up of women on low-dose flutamide (62.5 mg-125 mg) only 11% had deranged LFTs, and there were no cases of liver failure [50]. Another study found 6% of women had to be taken off flutamide for elevated transaminases (at a dose of 125–250 mg) [51]. All of these women were in the first year of therapy. It has been demonstrated to be superior to placebo and finasteride. It has also demonstrated similar levels of efficacy to spironolactone.
Evaluation of covalent binding of flutamide and its risk assessment using 19F-NMR
Published in Xenobiotica, 2021
Nobuyuki Kakutani, Takahiro Iwai, Yasushi Ohno, Satoru Kobayashi, Yukihiro Nomura
In this study, we developed a new approach to the covalent binding assay using NMR quantitation. We evaluated the extent of the covalent binding of a fluorine-containing drug, flutamide, an antiandrogen agent that interferes with the binding of androgen to its receptor. Flutamide is used to treat dysuria caused by prostatic hypertrophy as well as prostate cancer, which is promoted by androgens. However, flutamide has a risk for hepatic injury and a boxed warning message is written on the top of the drug description (Schering-Plough Research Institute, 2020). Retrospective analysis showed that a combination of dosage and forming rate of RMs is essential for predicting risk at the clinical usage and that flutamide is categorised as high risk (Nakayama et al., 2009). Flutamide can be used for NMR quantitation because it possesses a trifluoromethyl moiety, which is not metabolised and is present as an intense singlet spectrum by 19F-NMR spectrometry. We developed the assay using 19F-NMR instead of radiolabelled compounds and assessed the risk of flutamide using RM burden analysis (Kakutani et al., 2019). Comparing the values from the trapping assay, the traditional covalent binding assay using a radiolabelled tracer, and the covalent binding assay based on 19F-NMR quantitation, we evaluated the usefulness of 19F-NMR in the covalent binding assay. We concluded that the covalent binding assay using 19F-NMR and the risk assessment by RM burden predicted the risk of RMs in the early discovery stage.
Disruptions in the reproductive system of female rats after prenatal lipopolysaccharide-induced immunological stress: role of sex steroids
Published in Stress, 2019
V. M. Ignatiuk, M. S. Izvolskaya, V. S. Sharova, S. N. Voronova, L. A. Zakharova
From PND10 to PND21, to the end of the infantile period in rats, the large number of antral follicles forms. The granulosa cells begin to express gonadotropin receptors. Secretion of gonadotropins increases significantly in this period (Picut et al., 2015). Atresia (apoptosis) of a large number of antral and preovulatory follicles takes place during the prepubertal period. It has been observed that the secretion of LH decreases and serum estradiol concentration increases, indicating negative hormonal control feedback is established. Thence, the first ovulation, characterizing the pubertal period, takes place (Davis, Travlos, & McShane, 2001; Picut et al., 2015). Androgens may regulate follicular atresia both directly and indirectly (Walters & Handelsman, 2018). Chronically androgenized prepubertal female rats have ovarian follicular growth arrest, a high level of antral atresia (Kim et al., 2013) and delayed sexual development (Kim et al., 2002). Flutamide is an androgen-selective antagonist that blocks androgen receptors by inhibiting their translocation to the nucleus from the cytoplasm of the target cells, and it suppresses the negative effects of testosterone (Kim et al., 2002).