Gonadotropins (hMG, Menotropins & FSH, Urofollitropin)

  • Overview:gonadotropins
    • Human menopausal gonadotropins (hMG): Composition
      •  mixture, partially catabolized human FSH & LH {extraction -- postmenopausal women's urine}
      • standardized for FSH & LH content
      • used for treating infertility --
        •  in women: stimulation of ovarian follicle development
        •  in man: spermatogenesis
        •  both sexes: hMG must be used with luteinizing hormone (human chorionic gonadotropin, hCG) to ensure:
          • ovulation implantation women
          • testosterone production & full masculinization in men

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  • Pharmacokinetics:gonadotropins
    • 7-12 day course daily hMG or urofollitropin (simulating ovarian cycle follicular phase in women with hypothalamic amenorrhea) ®
      •  FSH levels increase to 2X baseline;
      •  LH levels increase to 1.5X baseline (hMG only; not with urofollitropin)

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  • Pharmacodynamics:gonadotropins
    • Women: hMG or FSH treatment of gonadotropin-deficient women ® ovarian follicular growth/maturation
      • Ovulation: chorionic gonadotropin requirement following follicular maturation
    • Men with gonadotropin deficiency: chorionic gonadotropin pre-treatment ®external sexual maturation
      • Subsequent hMG treatment ®spermatogenesis, fertility

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  • Clinical Use:gonadotropins
    • Indication: pituitary or hypothalamic hypergonadism with infertility
    • Population of anovulatory women would these conditions may benefit from human menopausal gonadotropin:

primary amenorrhea

secondary amenorrhea

polycystic ovary syndrome

anovulatory cycle
  • hMG & FSH: used in in vitro fertilization programs for ovarian hyperstimulation
  • Men with hypogonadotropic hypogonadism become fertile following hMG administration: success frequency = 50%.

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  •  Toxicity: gonadotropins
    • Ovarian overstimulation with hMG: ovarian enlargement (uncomplicated) -- frequency 20% of patients
    • "Hyperstimulation syndrome": more serious: frequency = 0.5-4%
      • hMG-induced ovarian enlargement
      • ascites
      • hydrothorax
      • hypovolemia (shock may occur)
      • hemoperitoneum (secondary to ruptured ovarian cyst)
      • fever
      • arterial thromboembolism
    • Possible abnormal development/premature corpus luteum degeneration in some patients
    • in men: gynecomastia -- occasionally

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Primary Reference: Fizgerald, P.A. and Klonoff, D.C. Hypothalamic and Pituitary Hormones, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 603-618.
Primary Reference:Biller, Beverly, M. K. and Daniels, Gilbert, H. Neuroendocrine Regulation and Diseases of the Anterior Pituitary and Hypothalamus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 1972-1998