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Endocrine Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
At the molecular level, CPA works by interacting with the AR as a competitive antagonist and a very weak partial agonist. It also interacts at the Progesterone Receptor (PR) and the Pregnane X Receptor (PXR) as an agonist, and at the Glucocorticoid Receptor (GR) as an antagonist. It also inhibits a number of enzymes involved in various steroidal synthesis and metabolic pathways including 3β-hydroxysteroid dehydrogenase, (3β-HSD)21-hydroxylase, 17α-hydroxylase and 17,20-lyase. The 3β-hydroxysteroid dehydrogenase and 21-hydroxylase enzymes are necessary for biosynthesis of the endogenous corticosteroids such as cortisol and aldosterone, and so their levels may be reduced. CPA also has a small direct inhibitory effect on 5α-reductase, which was the rationale for combining it with finasteride (a potent and selective 5α-reductase inhibitor) for the treatment of hirsutism. Finally, CPA has been found to bind nonselectively to opioid receptors (including the μ-, δ-, and κ- subtypes) which could explain the sedation sometimes observed with CPA treatment and/or the effectiveness of CPA in the treatment of cluster headaches.
Geriatric hair and scalp disorders
Published in Robert A. Norman, Geriatric Dermatology, 2020
Recent studies with 1 mg finasteride, a pure type II 5α-reductase inhibitor, have shown that it increases hair count and slows progression of androgenetic alopecia in 83% of males aged 18–41 years as measured by total hair count, increased percentage of anagen hairs in a target area53, global photographic assessment and investigator and subject assessment, with the effect maintained over two years54. Finasteride reduces serum dihydrotestosterone levels by 67%. Finasteride (Propecia®) was FDA approved in early 1998 for the treatment of men aged 18–41 years with androgenetic alopecia. The effect of finasteride on males 41–60 years old with androgenetic alopecia is currently being evaluated. A 1-year double-blind, placebo-controlled study using 1 mg finasteride in postmenopausal females 41–59 years of age with androgenetic alopecia yielded negative results. Treated and placebo groups both showed a slight net loss in hair count in the target area at one year55.
Erectile Dysfunction
Published in Botros Rizk, Ashok Agarwal, Edmund S. Sabanegh, Male Infertility in Reproductive Medicine, 2019
Mark Johnson, Marco Falcone, Tarek M. A. Aly, Amr Abdel Raheem
Furthermore, many medications are associated with impaired semen parameters and may cause ED (e.g., antidepressants and 5α-reductase inhibitors) [14]. These medications can be used to treat hypogonadism and may alter the hypothalamic-pituitary-gonadal (HPG) axis and subsequently affect production of mature spermatozoa. There is also an increased incidence of sexual dysfunction with psychotropic medications, including antidepressants and antipsychotics. Often these changes to the patients’ semen parameters are temporary; however, in some instances (e.g. the use of chemotherapy), the changes to the architecture of the testis and spermatozoa can be permanent. Ideally, these patients are offered semen cryopreservation prior to gonadotoxic treatments [14].
Development and optimization of a tamsulosin nanostructured lipid carrier loaded with saw palmetto oil and pumpkin seed oil for treatment of benign prostatic hyperplasia
Published in Drug Delivery, 2022
Rana B. Bakhaidar, Khaled M. Hosny, Imman M. Mahier, Waleed Y. Rizq, Awaji Y. Safhi, Deena M. Bukhary, Muhammad H. Sultan, Haitham A. Bukhary, Osama A. Madkhali, Fahad Y. Sabei
Apart from the proven role of PSO in BPH, the SP, or Serenoa repens, a palm that is found in the south coastal region of the United States, has also been extensively studied for treating BPH. Native Americans use it for various urinary and prostate problems. SP consists of various phytosterols, fatty acids, and vitamin E and acts via inhibiting 5α-reductase, cyclooxygenase, and 5-lipoxygenase. Additionally, SP has an antiproliferative effect against epithelial cells of the prostate (Governa et al., 2016). SP has been studied alone and in combination with other alpha-blockers and 5α-reductase inhibitors in clinical settings. In a multicentric trial, when SP extract was used for six months, marked improvement occurred in the International Prostate Symptom (IPSS) score and flow of urine (Giulianelli et al., 2012). Similarly, SP also showed long-term efficacy and safety against LUTS (Sinescu et al., 2011; Ye et al., 2019). Furthermore, based on Braeckman’s study, the use of SP oil for three months at a dose of 160 mg before bedtime (BD) improved the IPSS score to 22% and 35% after 45 and 90 days, respectively (Braeckman, 1994). In another study by Hong et al. (2009), the use of the combination of P and SP for 12 months in 47 Korean men significantly improved the IPSS score, improved the quality of life, reduced the serum prostate-specific antigen, improved the urinary flow rate.
Finasteride and androgenic alopecia; from therapeutic options to medical implications
Published in Journal of Dermatological Treatment, 2020
Ion G. Motofei, David L. Rowland, Mircea Tampa, Maria-Isabela Sarbu, Madalina-Irina Mitran, Cristina-Iulia Mitran, Anca Pantea Stoian, Camelia C. Diaconu, Stana Paunica, Simona R. Georgescu
Androgens, particularly the most active compound dihydrotestosterone, are related to various organic diseases (benign prostate hyperplasia, prostate cancer, acne, etc.) and several esthetic conditions (androgenic alopecia and hirsutism) (1). As a consequence, several antiandrogenic compounds have been synthesized and tested over time to treat these conditions. The most studied antiandrogenic drugs are represented by the class of 5α-reductase inhibitors which interfere in differing degrees (depending on the compound) with metabolism of testosterone to dihydrotestosterone. Although 5α-reductase inhibitors are commonly used to treat both androgenic alopecia (AGA) and benign prostatic hyperplasia (BPH), they are nevertheless somewhat controversial with respect to both their therapeutic efficacy and associated adverse reactions (2).
High serum concentration of estradiol may be a risk factor of prostate enlargement in aging male in China
Published in The Aging Male, 2020
Ding Xu, Yu Wu, Haibo Shen, Subo Qian, Jun Qi
Benign prostatic hyperplasia (BPH) is a common disorder among elderly men. While 50% of men beyond the age of 50 will develop histological BPH. It is characterized by the proliferation of epithelial and stromal cells, followed by enlargement of the gland [1], leading to frequent micturition, difficulties in initiating micturition, nycturia, a poor stream of urine, and a prolonged duration of micturition. Lasting data suggests that by the year 2025, about 50 million Americans will suffer from BPH symptoms [2], which in turn will raise healthcare expenses. So far, the etiology of BPH has not been fully explained [3]. Then, aging, sex hormones, and growth factors are generally considered to play important roles in the development of BPH [4]. It is worth mentioning the development of BPH is known to be sex steroid hormone-dependent. As we know, testosterone is converted to dihydrotestosterone (DHT) by the 5α-reductase enzyme, and higher DHT levels are associated with prostate enlargement [5]. Additionally, 5α-reductase inhibitors have been shown to be effective for reducing prostate volume, thereby demonstrating the importance of testosterone in prostate growth [6,7]. The curative way of BPH is focused on hormone.