Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0600142 (hot flushes)
 1,242 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, we reported that short term administration of a highly potent GnRH agonist (GnRHa) for 1 month to patients with polycystic ovarian disease (PCO) resulted in complete suppression of ovarian steroidogenesis without measurable effects on adrenal steroid production. This new study was designed to evaluate the effects of long term GnRHa administration in PCO patients with respect to their hormone secretion patterns and clinical responses. Eight PCO patients and 10 ovulatory women with endometriosis were treated daily with sc injections of [D-His6-(imBzl]),Pro9-NEt]GnRH (GnRHa; 100 micrograms) for 6 months. Their results were compared to hormone values in 8 women who had undergone bilateral oophorectomies. In response to GnRHa, PCO and ovulatory women had rises of serum LH at 1 month, after which it gradually declined to baseline. In both groups FSH secretion was suppressed throughout treatment. Serum estradiol, estrone, progesterone, 17-hydroxyprogesterone, androstenedione, and testosterone levels markedly decreased to values found in oophorectomized women by 1 month and remained low thereafter. In contrast, serum pregnenolone and 17-hydroxypregnenolone were partially suppressed, and dehydroepiandrosterone, dehydroepiandrosterone sulfate, and cortisol levels did not change. Clinically, hyperplastic endometrial histology in three PCO patients reverted to an inactive pattern, and proliferative endometrium in two other PCO patients became inactive in one and did not change in the other. Regression of proliferative endometrial histology occurred in all ovulatory women. Vaginal bleeding occurred in all women studied during the first month of GnRHa administration, after which all but one PCO patient became amenorrheic. Hot flashes were noted by all ovulatory women and by four of eight PCO patients. All PCO patients noted subjective reduction of skin oiliness, and five had decreased hair growth. We conclude that in premenopausal women: 1) chronic GnRHa administration results in apparently complete persistent suppression of ovarian steroid secretion; 2) adrenal steroid secretion is not influenced directly or indirectly; and 3) its use may be helpful in the treatment of endometrial hyperplasia and ovarian androgen excess in women with PCO.
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PMID:Clinical and hormonal effects of chronic gonadotropin-releasing hormone agonist treatment in polycystic ovarian disease. 311 31

This study was designed to evaluate the long-term effect (6 months) of the luteinizing hormone-releasing hormone (LH-RH) agonist buserelin on pituitary and ovarian function in a group of 14 patients presenting with the polycystic ovarian (PCO) syndrome. Buserelin was given subcutaneously 200 micrograms three times daily for the first 7 days followed by 500 micrograms once daily. Blood samples were taken weekly for the first month and then every month for radioimmunoassay of LH, FSH and sex steroids. While LH levels were stimulated during the first 2 weeks and then declined towards baseline, serum FSH levels were reduced after only 1 week (P less than 0.05). Serum oestradiol levels were maximally suppressed to the menopausal range after 1 month and testosterone levels were also significantly inhibited (P less than 0.05) after 2 weeks of therapy. Dehydroepiandrosterone (DHEA) sulphate did not show any significant change while 17-hydroxyprogesterone was suppressed after the first month of buserelin administration (P less than 0.01). The apparent divergent response of the gonadotrophins and the reduction of ovarian steroids in spite of lack of suppression of LH levels can be explained by the marked inhibition of the bioactivity of LH assessed by dispersed mouse Leydig cells assay. The clinical evaluation of hirsutism did not detect any change during the 6 month period. No patient had any menstrual bleeding or spotting after the sixth week of buserelin. The monthly incidence of hot flushes varied between 50 to 66%. This study shows that LH-RH agonist administration can selectively inhibit ovarian function and could be an interesting approach to evaluate the respective contribution of the ovary and adrenal on the pathophysiology of the polycystic ovarian disease. Polycystic ovarian (PCO) syndrome is characterized by tonic and exaggerated secretion of LH leading to an excessive stimulation of the ovarian stroma and an increased production of androgens (Yen et al., 1970; DeVane et al., 1975; Rebar et al., 1976). The androgen precursor delta 4 androstenedione is transformed in peripheral tissues into oestrone (Siiteri & MacDonald, 1973), thus maintaining the state of pituitary hypersensitivity and creating a positive feedback (Yen et al., 1976). The starting point of this vicious circle is still controversial; some argue for a hypothalamic abnormality (Vaitukaitis, 1983) while others support the peripheral origin of the hypersecretion of steroids (Reyniak, 1983). The importance of the adrenal contribution in this syndrome is still unclear.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Ovarian suppression in polycystic ovarian disease during 6 month administration of a luteinizing hormone-releasing hormone (LH-RH) agonist. 313 52