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The Gonadal Hormones & Inhibitors (■ THE OVARY (INHIBITORS &…

- - - - TABLE 40–5
    - - Replacement therapy in men: acne, sleep apnea, erythrocytosis, gynecomastia, decr in testicular size; alkylated androgens in high doses: peliosis hepatica, cholestasis, and hepatic failure. lower plasma HDL and may incr LDL. Hepatic adenomas and carcinomas reported. incr in hepatic Es plasma [ ]
      - most noticeable in women and prepubertal children. In women: hirsutism, acne, amenorrhea, clitoral enlargement, and deepening of the voice
  - - - Ketoconazole
    - - Fin[asteride]: BPH, prostate cancer ,hirsutism, early male pattern baldness; Dutasteride
      - abiraterone,
    - - F[lutamide]: potent antiandrogen used in prostatic carcinoma
      - Bicalutamide, nilutamide, and enzalutamide
      - Cyproterone and cyproterone acetate: used in women to treat hirsutism and in men to decrease excessive sexual drive
      - Spironolactone
- - - - Synthetic: incr oral effectiveness; Ethinyl estradiol (most potent)
      - Natural: sorted from highest potency: estra[di]ol (estradiol17β, E[2]), estr[one] (E[1]), and es[tri]ol (E[3])
    - - Cancer
      - Other Effects: Nausea and breast tenderness, Hyperpigmentation, incr frequency of migraine, cholestasis, gallbladder disease, and HTN.
      - Uterine Bleeding
  - - - mechs
        
        binds + can translocate androgen R into nucleus to initiate androgen-specific RNA synthesis
        
        does not inhibit aromatase
        
        incr mean clearance of progesterone
        
        inhibits midcycle surge of LH and FSH ; does not lower or suppress basal LH or FSH levels
      - adverse effects: bc of inherent glucocorticoid activity--> maybe adrenal suppression
    - - Anastrozole + Letrozole: selective nonsteroidal inhibitor of aromatase, effective in some women whose breast tumors have become resistant to tamoxifen
    - - Tamoxi[fen]: the first selective estrogen receptor modulator (SERM) introduced. mechanism of its mixed agonist/antagonist relations to estrogen receptor
      - Raloxifene
  - - - Natural: progesterone
      - Synthetic
        
        Table 40–2