title: Decline in insulin-like growth factor I levels after clomiphene citrate does not correct hyperandrogenemia in polycystic ovary syndrome.
abstract: It is widely accepted that the action of clomiphene citrate (CC) is mediated through its antiestrogenic properties on the hypothalamic-pituitary axis. Although insulin-like growth factor I (IGF-I) enhances the thecal cell response to LH, and estrogen treatment is associated with a reduction in IGF-I levels, CC is known to decrease circulatory IGF-I levels in polycystic ovary syndrome (PCOS) patients. The impact of lowering IGF-I levels on androgen levels in PCOS is unknown. This study was designed to examine the impact of CC treatment on the interrelationships of IGF-I, androgens, and estrogens in normal subjects and patients with PCOS. IGF-I, gonadotropin, androgen, estrogen, and sex hormone-binding globulin levels were measured in 8 PCOS patients and 10 normal subjects before and after treatment with the antiestrogen CC. Studies were performed in the early follicular phase, days 4-6 of the menstrual cycle in normal subjects. In normal subjects, CC treatment led to a significant increase in estradiol (84 +/- 10 to 234 +/- 62 pmol/L, untreated and CC treated; P < 0.05) and estrone (125 +/- 14 to 257 +/- 29 pmol/L; P < 0.05) levels with a significant lowering of IGF-I levels (297 +/- 25 to 230 +/- 17 micrograms/L; P < 0.05). Similarly, in PCOS patients a significant increase in estradiol (110 +/- 11 to 245 +/- 58 pmol/L; P < 0.05) and estrone (301 +/- 32 to 401 +/- 90 pmol/L; P < 0.05) levels and a significant lowering of IGF-I levels (330 +/- 43 to 214 +/- 27 micrograms/L; P < 0.05) were observed after CC treatment. However, no significant correlation was observed between changes in IGF-I and changes in estradiol in either group. Compared to pretreatment levels, no significant changes in the following parameters were observed after 5 days of CC treatment in either study group: testosterone, testosterone/sex hormone-binding globulin ratio, and androstenedione. The relationship among CC treatment, gonadotropin, estrogen, and IGF-I levels is complex. Changes in blood IGF-I levels are not associated with changes in androgen levels, although paracrine and or autocrine effects cannot be excluded.
authors.affiliation: Department of Investigative Endocrinology, University College, Dublin, Ireland.
authors.forename: T M
authors.initials: TM
authors.lastname: Fiad
authors.forename: T P
authors.initials: TP
authors.lastname: Smith
authors.forename: S K
authors.initials: SK
authors.lastname: Cunningham
authors.forename: T J
authors.initials: TJ
authors.lastname: McKenna
mesh_terms: D000328:Adult; D000728:Androgens / Q000378:metabolism*; D016022:Case-Control Studies; D002996:Clomiphene / Q000627:therapeutic use*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005300:Fertility Agents, Female / Q000627:therapeutic use*; D006062:Gonadotropins / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000188:drug therapy*; D012636:Secretory Rate / Q000187:drug effects
chemical_list: D000728:Androgens; D004967:Estrogens; D005300:Fertility Agents, Female; D006062:Gonadotropins; D002996:Clomiphene; D007334:Insulin-Like Growth Factor I