CLOMIPHENE CITRATE IN MEN: INCREASE OF CORTISOL, LUTEINIZING HORMONE, TESTOSTERONE AND STEROID-BINDING GLOBULINS

1972 ◽  
Vol 53 (2) ◽  
pp. 261-276 ◽  
Author(s):  
J. C. MARSHALL ◽  
D. C. ANDERSON ◽  
C. W. BURKE ◽  
A. GALVAO-TELES ◽  
T. RUSSELL FRASER
Keyword(s):  
Luteinizing Hormone ◽  
Plasma Cortisol ◽  
Specific Binding ◽  
Clomiphene Citrate ◽  
Normal Subjects ◽  
Sex Hormone Binding Globulin ◽  
Total Cortisol ◽  
Serum Luteinizing Hormone ◽  
Steroid Binding ◽  
Normal Men

SUMMARY The effects of clomiphene citrate were studied in nine normal men, in three patients with partial panhypopituitarism, and in four patients with isolated gonadotrophin deficiency. The administration of this drug to the normal subjects in a dosage of 3 mg/kg/day for 10 days resulted in a mean rise in serum luteinizing hormone (LH) of 107%, in plasma 17β-hydroxyandrogens (17-OHA) of 114%, and in plasma total cortisol of 86%. The rise of testosterone concentration in normal subjects was associated with a doubling of the non-protein bound fraction, and also with increased binding of testosterone to sex hormone-binding globulin (SHBG). In contrast, plasma non-protein bound and urinary unconjugated cortisol remained unchanged. The percentage of plasma cortisol not bound to protein fell, indicating that the rise in total plasma cortisol was secondary to increased protein binding. This was confirmed by finding increased binding of both cortisol and testosterone to their specific binding globulins at 1 °C, due apparently to increased concentrations of SHBG and corticosteroid-binding globulin after clomiphene administration. All the responses to clomiphene were prevented by simultaneous administration of fluoxymesterone in two normal subjects. All the hypopituitary patients showed no rise of LH, 17-OHA or cortisol. The hypogonadotrophic patients, however, showed a normal total cortisol rise. It is suggested that clomiphene has two actions. First, it interferes with the hypothalamic feed-back mechanisms for testosterone, resulting in increased LH secretion, and secondly it has an oestrogen-like effect in stimulating production of steroid-binding globulins.

ÉTUDES IN VIVO SUR LE MÉTABOLISME DES ANDROGÉNES APRES ADMINISTRATION DE STÉROÏDES INHIBITEURS DE L'OVULATION

1965 ◽  
Vol 50 (1) ◽  
pp. 131-144 ◽  
Author(s):  
P. Mauvais-Jarvis ◽  
M. F. Jayle ◽  
J. Decourt ◽  
J. Louchart ◽  
J. Truffert
Keyword(s):  
Luteinizing Hormone ◽  
Urinary Excretion ◽  
Normal Subjects ◽  
Hormone Activity ◽  
Testosterone Production ◽  
Normal Men ◽  
Ethinyl Oestradiol

ABSTRACT Normal subjects and hirsute women with micropolycystic ovaries were treated with ethinyl-oestrenol + 3-methoxy-ethinyl-oestradiol (Lyndiol®), in view of studying the action of this compound on the production of androgens and on the urinary excretion of their metabolites. In normal men, the production of testosterone and the excretion of androsterone and aetiocholanolone are suppressed, whereas the excretion of other 17-ketosteroids and the production of dehydroepiandrosterone sulphate are unchanged. Moreover, the luteinizing hormone activity (LH) in plasma is depressed. It seems that the preparation inhibits specifically the testicular androgen production, by suppressing the hypothalamo-hypophyseal control of LH. Testosterone production and urinary 17-ketosteroid excretion are modified in the same way in women with Stein-Leventhal's syndrome. Physiopathological and therapeutical implications which come from these results are discussed.

THE SECRETION, INTERCONVERSION AND CATABOLISM OF CORTISOL, CORTISONE AND SOME OF THEIR METABOLITES IN MAN

1969 ◽  
Vol 62 (2) ◽  
pp. 339-359 ◽  
Author(s):  
E. Bailey ◽  
H. F. West
Keyword(s):  
Plasma Cortisol ◽  
Normal Subjects ◽  
Secretion Rate ◽  
Main Site ◽  
Rheumatoid Arthritic ◽  
Specific Activities ◽  
Normal Men ◽  
The Given ◽  
Secretion Rates ◽  
Conjugated Metabolites

ABSTRACT Trace doses of one or more of the following radioactive steroids were given to 2 normal and 4 rheumatoid arthritic men: cortisol, cortisone, 20α-dihydrocortisol, 20β-dihydrocortisol and tetrahydrocortisol. The specific activities of the given steroids and some of their unconjugated and conjugated metabolites in urine were measured. The secretion rates of cortisol and cortisone for the 2 normal men, deduced from their specific activities in urine, were found to be approximately equal and in sum approximately equal to the secretion rate of cortisol deduced from the specific activities of their conjugated metabolites. Evidence of the speed of interconversion of cortisol and cortisone was obtained by giving [4-14C] cortisol and [1,2-3H] cortisone simultaneously to the 2 normal subjects and measuring the specific activities of the cortisol and cortisone in urine; also by measuring, in one subject, the proportion of 14C and 3H in plasma cortisol and cortisone at intervals after administration. The specific activities were similar, the plasma cortisone was approximately 50 % derived from cortisol at 30 min and the plasma cortisol 40 % derived from cortisone at 40 min. For both the normal subjects given 14C-cortisol and 3H-cortisone the specific activities of the urinary unconjugated metabolites were consistently and markedly higher than those of the hydrolysed conjugated metabolites. The combined secretion rate of 20α- and 20β-dihydrocortisol and tetrahydrocortisol, for one normal subject, was estimated to be approximately 4 mg/24 h. It is suggested that the findings are consistent with the hypotheses that under basal unstressed conditions, 1, cortisol and cortisone are secreted by the adrenal in approximately equal amount; 2, cortisol and cortisone are interconverted at a speed that precludes the liver from being the main site of the interconversion; 3, the major fractions of the unconjugated and conjugated cortisol and cortisone metabolites are formed at different sites.

Differences in Serum Luteinizing Hormone Measurements by Immunoradiometric Assay Induced by Kinetic Manipulation of Assay Conditions are Dependent on the Endocrine Milieu of Serum

1996 ◽  
Vol 33 (2) ◽  
pp. 107-111
Author(s):  
A O Olukoga ◽  
R Mitchell ◽  
L Walton ◽  
W R Robertson ◽  
I Laing
Keyword(s):  
Luteinizing Hormone ◽  
Polycystic Ovarian Syndrome ◽  
Immunoradiometric Assay ◽  
Serum Samples ◽  
Serum Luteinizing Hormone ◽  
Endocrine Status ◽  
Reference Preparation ◽  
Normal Men ◽  
Ovarian Syndrome ◽  
Assay Conditions

Divergent estimates for luteinizing hormone (LH) in individual serum samples may be given by different immunoassays. In order to investigate this phenomenom further, we have studied the effect of differences in assay kinetics within the same immunoradiometric assay (IRMA) configuration on LH measurement in sera from different endocrine states. Three pairs of monoclonal/polyclonal two-site IRMA systems for LH were developed from three LH monoclonal antibodies and a common polyclonal anti-human chorionic gonadotrophin. For IRMA systems a short and long assay, which were different only with respect to the incubation time (1/2 h and overnight respectively), of the labelled monoclonal first antibody were performed. The IRMAs were all standardized against the LH international reference preparation 68/40. LH concentrations were measured by all the IRMAs in sera obtained from normal men ( n = 11) and from women with polycystic ovarian syndrome (PCO; n = 13). In normal men, there were no differences in LH estimates between the short and the long assays of the three IRMA systems, and the ratios of long to short assays were similar for all the systems. However, in PCO there were significant differences between short and long assays and the ratios of long to short assays were different for the IRMA systems. These results indicate that kinetic differences between IRMAs of the same antibody configuration can be associated with differences in measured LH concentrations, depending on the endocrine status of the sera studied. As LH glycoform patterns are known to differ between normal men and PCO, the observed changes in LH estimates may be due to the different glycoform composition.

scholarly journals Decline in Insulin-Like Growth Factor I Levels after Clomiphene Citrate Does Not Correct Hyperandrogenemia in Polycystic Ovary Syndrome

1998 ◽  
Vol 83 (7) ◽  
pp. 2394-2398 ◽  
Author(s):  
Tarek M. Fiad ◽  
Thomas P. Smith ◽  
Sean K. Cunningham ◽  
T. Joseph McKenna
Keyword(s):  
Polycystic Ovary ◽  
Clomiphene Citrate ◽  
Normal Subjects ◽  
Sex Hormone Binding Globulin ◽  
Hormone Binding ◽  
Ovary Syndrome ◽  
Factor I ◽  
Igf I ◽  
The Impact ◽  
Androgen Levels

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 μg/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 ± 27μ g/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.

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