Effect of low-dose oral contraceptive on gonadotropins, androgens, and sex hormone binding globulin in nonhirsute women. Effect of low-dose oral contraceptives on androgenic markers and acne. The effect of combination therapy with metformin and combined oral contraceptives (COC) versus COC alone on insulin sensitivity, hyperandrogenaemia, SHBG and lipids in PCOS patients. Effects of a monophasic combined oral contraceptive containing nomegestrol acetate and 17β-oestradiol in comparison to one containing levonorgestrel and ethinylestradiol on markers of endocrine function Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone. Impact of oral contraceptives on sex hormone-binding globulin and androgen levels: a retrospective study in women with sexual dysfunction. Effect of two oral contraceptives containing ethinylestradiol and gestodene or norgestimate upon androgen parameters and serum binding proteins. [Ovarian suppression with Diane 35/50]. Effects of oral contraceptive combinations containing levonorgestrel or desogestrel on serum proteins and androgen binding. The effect of monophasic combinations of ethinyl estradiol and norethindrone on gonadotropins, androgens and sex hormone binding globulin: a randomized trial. Combined oral contraceptive treatment of adolescent girls with polycystic ovary syndrome. Lipid profile. Correlation of biochemical markers and clinical signs of hyperandrogenism in women with polycystic ovary syndrome (PCOS) and women with non-classic congenital adrenal hyperplasia (NCAH) A randomized cross-over study on various hormonal parameters of two triphasic oral contraceptives. Comparative evaluation of the androgenicity of four low-dose, fixed-combination oral contraceptives. Clinical and hormonal effects of two contraceptives: correlation to serum concentrations of levonorgestrel and gestodene. Interrelationships between plasma testosterone, SHBG, IGF-I, insulin and leptin in prostate cancer cases and controls Different effects of tibolone and continuous combined estrogen plus progestogen hormone therapy on sex hormone binding globulin and free testosterone levels – an association with mammographic density Placebo-controlled comparison of hormonal and biochemical effects of danazol and high-dose medroxyprogesterone acetate. Body mass index, circulating levels of sex-steroid hormones, IGF-I and IGF-binding protein-3: a cross-sectional study in healthy women. Changes in androgens during treatment with four low-dose contraceptives. [Effect of ethinyl estradiol-dienogest combination on serum androgen concentrations]. Comparative effects of oral esterified estrogens with and without methyltestosterone on endocrine profiles and dimensions of sexual function in postmenopausal women with hypoactive sexual desire. Oral contraceptive tablets containing 20 and 30 micrograms of ethinyl estradiol with 150 micrograms desogestrel. Their influence on lipids, lipoproteins, sex hormone binding globulin and testosterone.
The effectiveness of a low-dose oral contraceptive ( OC ) in suppressing plasma levels of gonadotropins , ovarian , and adrenal and rogens and stimulating sex hormone-binding globulin ( SHBG ) was evaluated prospect ively in nonhirsute women . Thirty-three women ingested 35 micrograms of ethinyl estradiol and 1 mg of norethindrone beginning within day 1 to 5 of the menstrual cycle . Baseline levels of luteinizing hormone , follicle-stimulating hormone , total testosterone ( T ) , and rostenedione ( A ) , dehydroepi and rosterone sulfate ( DHEAS ) , and SHBG were obtained before ingestion of the OC and repeated after 3 , 6 and , 9 months of OC use on day 1 to 5 of the OC " cycle " . A significant suppression of gonadotropin levels is seen in nonhirsute women .  Sex hormone binding globulin is consistently stimulated by the low-dose OC . A significant suppression of T and DHEAS is observed . No change was seen in levels of A. The demonstrated effects become evident at 3 months and are maintained at 6 and 9 months Oral contraceptives ( OC ) suppress excess and rogen production ; however , different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin ( SHBG ) and testosterone that may influence clinical outcomes . This multicenter , open-label , r and omized study compared biochemical and rogen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol ( EE , 20 micrograms ) but different progestins , levonorgestrel ( LNG , 100 micrograms ) , and norethindrone acetate ( NETA , 1000 micrograms ) . Fifty-eight healthy women ( 18 - 28 years old ) received three cycles of treatment with LNG/EE ( n = 30 ) or NETA/EE ( n = 28 ) . The results showed that LNG reduced and rogen levels in three compartments -- adrenal , ovarian , and peripheral . NETA reduced only adrenal and peripheral and rogens . Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG , bioavailable testosterone ( T ) was reduced by the same amount with LNG and NETA . Both treatments improved acne and were well tolerated . Low-dose OC ( EE , 20 micrograms ) are effective in reducing circulating and rogens and acne lesions without causing weight gain . Although LNG and NETA affected secondary markers differently , both OC formulations produced an equivalent decrease in bioavailable BACKGROUND Neither oral contraceptives ( COC ) nor metformin are an optimal modality for the long-term treatment of polycystic ovary syndrome ( PCOS ) . The aim of this study was to evaluate whether a combination of both is beneficial over COC monotherapy . METHODS Altogether , 30 women were included in the study and 28 finished the protocol . The patients were r and omly assigned to two groups treated with either COC ( COC group ) or COC and metformin ( 1500 mg/day ) ( METOC group ) for 6 months . Anthropometric parameters , and rogens , lipids , fasting insulin , glucose and sex hormone binding globulin ( SHBG ) concentrations were measured before and at the end of the sixth cycle of treatment . The insulin sensitivity index was evaluated using the euglycaemic clamp . RESULTS There were no significant changes in anthropometric parameters , fasting glucose or insulin sensitivity in either group . Total testosterone , free and rogen index , and rostenedione and dehydroepi and rosterone decreased and SHBG increased significantly in both groups . When comparing the effect of both treatments , only a more pronounced decrease in free and rogen index was found in the METOC group . CONCLUSIONS Adding metformin slightly modified the treatment effect of COC , causing a more significant decrease in the free and rogen index but having no additional positive impact on lipids , insulin sensitivity , SHBG or testosterone . The available data do not offer enough evidence to advocate the st and ard use of combined treatment in PCOS . Whether the combination might be beneficial for specific subgroups of patients is of further interest ABSTRACT Objectives To compare the effects of two monophasic combined oral contraceptives , containing either nomegestrol acetate/17β-oestradiol ( NOMAC/E2 ) or levonorgestrel/ ethinylestradiol ( LNG/EE ) on endocrine function , and rogens , and sex hormone-binding globulin ( SHBG ) . Methods R and omised , open-label , multi-centre trial involving 121 healthy women , aged 18–50 years old . Participants received NOMAC/E2 ( 2.5 mg/1.5 mg ) in a 24/4-day regimen ( n = 60 ) or LNG/EE ( 150 μg/30 μg ) in a 21/7-day regimen ( n = 61 ) for six cycles . The primary outcome was the change from baseline to cycle 6 in markers of adrenal and thyroid function , and rogens , and SHBG . Results Total cortisol , corticosteroid-binding globulin ( CBG ) , and thyroxine-binding globulin ( TBG ) increased from baseline in both groups , with significantly greater increases in the LNG/EE group . No relevant changes from baseline or differences between the groups were observed for thyroid-stimulating hormone ( TSH ) and free thyroxine ( T4 ) . And rogens and and rogen precursors decreased from baseline in both groups , with significantly greater decreases in the LNG/EE group ( except for free testosterone ) . A greater increase in SHBG was observed with NOMAC/E2 than with LNG/EE . Conclusions NOMAC/E2 has significantly less influence on markers of adrenal and thyroid function and and rogens than LNG/EE . The clinical relevance of these findings requires further study The effect of seven low-dose oral contraceptive preparations on sex hormone binding globulin ( SHBG ) , cortisol binding globulin ( CBG ) , total and absolute free testosterone were investigated in groups of 10 healthy volunteers . All preparations contained about the same amount of ethinylestradiol but they differed in type and /or dose of progestagen . The progestagens studied were : levonorgestrel ( LNG ; in mono- and triphasic preparations ) , norethisterone ( NET ; in monophasic preparation ) , desogestrel ( DSG ; in mono- and biphasic preparations ) and gestodene ( GSD ; in triphasic preparation ) , all 19-nortestosterone derivatives , and the anti- and rogen cyproterone acetate ( CPA ) in a monophasic preparation . Differences observed in SHBG level , which reflect the estrogen- and rogen balance , can be attributed to the intrinsic and rogenic ( or anti- and rogenic ) properties of the progestagens , and were in agreement with the results of published receptor binding studies , performed in vitro . Based on our results the following ranking ( high to low ) can be made with respect to the and rogenicity of the preparations : monophasic LNG greater than or equal to monophasic NET = triphasic LNG greater than or equal to triphasic GSD = biphasic DSG = monophasic DSG greater than monophasic CPA . An anti-estrogenic effect of the 19-nortestosterone derived progestagens can be excluded by the effect on CBG , a marker for estrogenic activity . All preparations containing a 19-nortestosterone derived progestagen , independent of their type and dose , induce a similar rise in CBG , whereas the preparation with cyproterone acetate induced an even higher CBG level . Irrespective of the effect on total testosterone , which varies between the preparations , the absolute free testosterone level decreased to a comparable degree for all preparations . ( ABSTRACT TRUNCATED AT 250 WORDS INTRODUCTION Oral contraceptives ( OCs ) have been the preferred method of birth control because of their high rate of effectiveness . OC use , however , has been associated with women 's sexual health complaints and and rogen insufficiency . OC use is associated with a decrease of and rogen ovarian synthesis and an increase in the production of sex hormone-binding globulin ( SHBG ) . There have been limited studies assessing SHBG values after discontinuation of OC use . AIM To retrospectively investigate SHBG levels before and after discontinuation of OC use . MAIN OUTCOME MEASURE Sex hormone-binding globulin values were compared at baseline , while on the OC , and well beyond the 7-day half-life of SHBG at 49 - 120 ( mean 80 ) days and > 120 ( mean 196 ) days after discontinuation of OCs . METHODS A total of 124 premenopausal women with sexual health complaints for > 6 months met inclusion /exclusion criteria . Three groups of women were defined : ( i ) " Continued-Users " ( N = 62 ; mean age 32 years ) had been on OCs for > 6 months and continued taking them ; ( ii ) " Discontinued-Users " ( N = 39 ; mean age 33 years ) had been on OCs for > 6 months and discontinued them ; and ( iii ) " Never-Users " ( N = 23 ; mean age 36 years ) had never taken OCs . RESULTS Sex hormone-binding globulin values in the " Continued-Users " were four times higher than those in the " Never-User " group ( mean 157 + /- 13 nmol/L vs. 41 + /- 4 nmol/L ; P < 0.0001 ) . Despite a decrease in SHBG values after discontinuation of OC use , SHBG levels in " Discontinued-Users " remained elevated in comparison with " Never-Users " ( N = 26 ; P < 0.0001 for > 120 days ) . CONCLUSION In women with sexual dysfunction , SHBG changes in " Discontinued-Users " did not decrease to values consistent with " Never-Users . " Long-term sexual , metabolic , and mental health consequences might result as a consequence of chronic SHBG elevation . Does prolonged exposure to the synthetic estrogens of OCs induce gene imprinting and increased gene expression of SHBG in the liver in some women ? Prospect i ve research is needed The effect of a triphasic oral contraceptive containing ethinylestradiol and gestodene ( EE/GSD ) on various serum hormonal parameters was compared with that of a monophasic formulation containing 35 micrograms ethinylestradiol and 250 micrograms norgestimate ( EE/NGM ) . Blood sample s were collected from 46 women on days 2 , 11 , and 21 of the preceding control cycle and of the third , sixth and twelfth treatment cycle . There was no significant difference in the influence on any hormonal parameter between both formulations . Both EE/GSD and EE/NGM caused a time-dependent suppression of serum dehydroepi and rosterone sulphate ( DHEA-S ) by 20 - 30 % ( p < 0.01 ) and a reduction of 5 alpha- and rostane-3 alpha , 17 beta-diol glucuronide by 50 - 60 % ( p < 0.01 ) during each treatment cycle , while and rostenedione levels were reduced by 25 % ( p < 0.01 ) . There was also a significant decrease in the levels of total testosterone by 30 - 35 % ( p < 0.01 ) and free testosterone by 60 % ( p < 0.01 ) , while sex hormone-binding globulin ( SHBG ) was increased by 200 - 240 % on days 11 and 21 ( p < 0.01 ) . During the pill-free interval the SHBG levels were reduced to a certain degree but remained elevated by 100 % as compared to the pretreatment values . The serum levels of corticosteroid-binding globulin ( CBG ) which is known to be influenced only by the estrogenic component of combination pills , increased significantly by 170 % ( p < 0.01 ) during each treatment cycle . During the pill-free interval of 7 days , the CBG levels decreased but were still elevated by 90 - 100 % as compared to the control cycle . Similarly , the serum levels of cortisol were significantly elevated by 110 - 140 % ( p < 0.01 ) during treatment with both preparations . The results demonstrate a profound suppression of and rogen levels and peripheral and rogen metabolism In this study , hormone profiles were studied using Diane 35 and Diane 50 before and after treatment for 4 - 25 months . A comparison of the hormone profiles with Diane 35 or Diane 50 should investigate , if both preparations induce complete ovarian suppression , independent of the given dose of ethinyl oestradiol .  43 patients were treated with Diane 35 and 15 women with Diane 50  over a different lengths of time -- up to a period of 25 cycles . Parallel to the determination of the hormone profiles ( luteinising hormone [ LH ] , follicle stimulating hormone [ FSH ] , prolactin , oestrone [ E1 ] , oestradiol [ E2 ] , progesterone , total testosterone [ T. T. ] , free testosterone [ F. T. ] , dehydroepi and rosterone-sulfate [ DHEA-S ] , delta-4- and rostenedione [ A. ] and sex hormone binding globulin [ SHBG ] ) , observations on the and rogen symptoms before treatment and their course during therapy were made . Moreover , the ratios of LH/FSH and E1/E2 as well as the and rogenic index , the ratio of total testosterone/SHBG were determined as control of treatment effects . The most important hormonal changes , which had been observed during a period up to two years are the following : --LH and FSH suppression -- prolactin with increasing tendency -- decrease of the total and rogens and free testosterone-- decrease of the oestrogens E1 , E2 - -increase of SHBG . The confirmation of the efficacy of the anti- and rogen/oestrogen combination was reflected by the decline of the and rogenic index in all groups . Acne and seborrhoe improved after 3 - 4 cycles ; alopecia after 8 - 9 cycles and hirsutism diminished after 3 cycles of treatment . In spite of different doses of the combined preparations with 2 mg cyproteronacetate and 0.035 or 0.050 mg ethinyloestradiol , no difference in ovarian suppression as well clinical effects could be found The effects of the oral contraceptive combinations 0.125 mg Org 2969 ( desogestrel ) ( 13-ethyl-11-methylene-18,19-dinor-17alpha-pregn-4-en-20-yn-17-ol ) + 0.05 mg ethinyloestradiol ( EE ) and 0.125 mg levonorgestrel + 0.05 mg EE on serum sex-hormone-binding globulin ( SHBG ) , ceruloplasmin , transcortin and ratio free testosterone over total testosterone ( percentage free testosterone ) and ratio free 5alpha-dihydrotestosterone over total 5alpha-dihydrotestosterone ( percentage free 5alpha-dihydrotestosterone ) were compared in healthy female volunteers . Treatment was r and omly distributed over the volunteers ; 11 women received  Org 2969 + EE  and 11 women received  levonorgestrel + EE . These combinations induced similar increases in transcortin levels ( 115 and 140 % ) and ceruloplasmin levels ( 115 and 123 % ) after 3 months of treatment . However , the combination Org 2969 + EE induced a substantial increase ( 213 % ) in SHBG capacity after 3 months of treatment , whereas a smaller increase ( 80 % ) was observed with levonorgestrel + EE . A return to pretreatment values was observed 2 months after termination of treatment for all parameters . The difference in the effects of both preparations oh SHBG was statistically significant and can be best explained by a difference in the and rogenicity of the progestogens . A good correlation was free testosterone and the reciprocal value of the percentage free 5 alpha-dihydrotestosterone . These results confirm that SHBG is the major regulator of the biologically active free and rogen fraction in women before , during and after combined oral contraceptive treatment The effects of different monophasic combinations of ethinyl estradiol and norethindrone on FSH , LH , sex hormone binding globulin , total testosterone , and rostenedione , and dehydroepi and rosterone sulfate levels in non-obese , non-hirsute women were compared . Retrospective analysis of frozen serum from a prospect i ve r and omized trial in which women received one of three oral contraceptive pills containing ethinyl estradiol 50 micrograms/norethindrone 1 mg , ethinyl estradiol 35 micrograms/norethindrone 1 mg or ethinyl estradiol 35 g/norethindrone 0.5 mg for nine cycles was conducted . Blood sample s were obtained prior to treatment and during the third , sixth and ninth pill cycles . Ethinyl estradiol 50 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 1 mg suppressed FSH , LH , and total testosterone and increased sex hormone binding globulin to a similar degree . Ethinyl estradiol 35 micrograms/norethindrone 0.5 mg result ed in less suppression of FSH , LH , and total testosterone , but greater elevation of sex hormone binding globulin . Dehydroepi and rosterone sulfate was suppressed to a similar degree with ethinyl estradiol 35 micrograms/norethindrone 1 mg and ethinyl estradiol 35 micrograms/norethindrone 0.5 mg , but ethinyl estradiol 50 micrograms/norethindrone 1 mg result ed in the least suppression of dehydroepi and rosterone sulfate .  Ethinyl estradiol 35 micrograms/norethindrone 1 mg caused greater suppression of and rostenedione than did the other two oral contraceptives . Oral contraceptive-induced changes in gonadotropins , and rogens , and sex hormone binding globulin can be predicted by considering the relative amounts of estrogen and progestin in the pill . When combined with 1 mg of norethindrone , 50 micrograms of ethinyl estradiol did not result in greater suppression of FSH , LH , or total testosterone or in greater elevation of sex hormone binding globulin than did 35 micrograms of ethinyl estradiol The clinical signs and neuroendocrine features of adolescents with polycystic ovary syndrome ( PCOS ) resemble those found in adult women with PCOS . These adolescent patients are c and i date s for long-term treatment by one of the different therapeutic approaches that have been proposed . It is therefore essential that the treatment does not induce unfavorable metabolic effects . We investigated and compared the effects of cyproterone acetate ( CA ) and desogestrel ( D ) , as part of combined oral contraceptives ( COC ) , on lipid metabolism and hirsutism in adolescents with PCOS . Twenty-four girls with clinical signs of PCOS were recruited . They were all hyper and rogenic and euthyroid and had normal prolactin plasma levels . Non-classic congenital adrenal hyperplasia was ruled out by the ACTH stimulation test . Blood sample s were obtained for sex hormone binding globulin ( SHBG ) , total cholesterol ( TC ) , LDL cholesterol , HDL cholesterol , triglycerides ( TGs ) , apolipoproteins A-I , A-II , B , and lipoprotein ( a ) ( Lp(a ) ) measurements . After the initial examination , therapy was initiated in a r and omly selected order ( 12 and 12 patients were treated daily by 2 mg CA and 0.150 mg D , respectively , plus 0.035 and 0.030 mg ethinylestradiol , respectively ) . The degree of hirsutism and the lipid profile were reevaluated every 3 months after initiation of therapy for 1 year . Our data show that after 12 months of treatment with the D or CA COC , the Ferriman-Gallway hirsutism score decreased and TC and LDL-C increased . TGs and HDL-C were raised significantly in the CA COC group , whereas apolipoprotein A1 increased during D COC treatment . The atheromatic indices did not change . These data suggest that treatment of adolescent girls with PCOS is comparably effective with the two contraceptive formulations and that the desogestrel COC could be considered in the treatment of adolescent PCOS patients because it does not have side effects on lipid metabolism Background : Polycystic ovary syndrome ( PCOS ) is the most common cause of hyper and rogenism in women . Non-classic congenital adrenal hyperplasia ( NCAH ) is very close to PCOS . The diagnosis of hyper and rogenism is not based on the finding of decreased or increased levels of a single hormone . Objective : In our paper , we are going to test correlation between clinical signs and biochemical markers of hyper and rogenism . Material s and Methods : In this prospect i ve study , we calculated  free testosterone ( cFT ) , bioavailable testosterone ( cBT ) , free and rogen index ( FAI ) , free estrogen index ( FEI ) , total testosterone ( TT ) , sex-hormone binding globulin ( SHBG ) , estradiol ( E2 ) , dehydroepi and rosterone-sulfat ( DHEA-S ) , 17α -hydroxyprogesterone ( 17α -OHP ) , prolactin ( P ) , C-peptid and homeostasis model assessment for insulin resistance ( Homa-IR ) were measured in two groups of young untreated women with PCOS and NCAH . Results : In our research , we did not find any significant differences between PCOS and NCAH groups by age , hormonal and calculated parameters of and rogens . Waist to hip ratio ( WHP ) and body mass index ( BMI ) values were higher in the group of patients with PCOS than NCAH group . But in all patients we found positive correlation between hirsutism score and FAI , cFT , cBT , as well as we found negative correlation between hirsutism score and SHBG . We also tested hormonal and calculated parameters of and rogens between PCOS patients by upper body and lower body obesity , but we did not find any significant differences . There was not any difference by the hirsutism score in these groups either . Conclusion : In our research we found that the calculated values of cFT , cBT and FAI are helpful for determinate hirsutism score in all hirsute patients , despite of ovarian or adrenal hyper and rogenemia The effect of two triphasic oral contraceptives ( Triquilar [ TRQ ] and Trisiston [ TRS ] ) containing ethinyl estradiol ( EE ) and levonorgestrel ( LNG ) on various hormonal parameters was investigated in 26 women during a cross-over study .  TRS consisted of 0.03 mg EE + 0.05 mg LNG ( six tablets ) , 0.04 mg EE + 0.075 mg LNG ( six tablets ) , and 0.03 mg EE + 0.15 mg LNG ( nine tablets ) , whereas TRQ was different in the second phase ( five tablets ) and third phase ( 10 tablets ) . Blood sample s were taken on days 6 , 11 , 21 , and 28 of the control and washout cycles and the third treatment cycle . Both formulations inhibited ovulation reliably and decreased the serum levels of gonadotropins , free testosterone , and dehydroepi and osterone sulfate in a time-dependent manner , whereas estradiol and testosterone were already suppressed on day 6 , indicating a direct suppressive effect on ovarian steroid synthesis . Prolactin , which rose sporadically in some women , was not significantly changed . In contrast , the levels of sex hormone binding globulin , corticosteroid binding globulin , and cortisol were significantly elevated by 100 % . During the hormone-free interval of 7 days , all parameters returned at least partly to baseline . There was no significant difference between the effects of both formulations . The results suggest the possibility of a direct inhibitory effect of contraceptive steroids on ovarian steroid synthesis Changes in endogenous and rogen metabolism were compared in healthy women taking one of four low-dose modern oral contraceptives ( OCs ) . One hundred women were r and omized to ( 1 ) 35 micrograms ethinyl estradiol ( EE ) + 250 micrograms norgestimate ( Cilest ) ; ( 2 ) 20 micrograms EE + 150 micrograms desogestrel ( Mercilon ) ; ( 3 ) 30 micrograms EE + 150 micrograms desogestrel ( Marvelon ) ; or ( 4 ) 30 micrograms EE + 75 micrograms gestodene ( Femodene ) . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded , and plasma levels of the following variables were recorded : sex-hormone-binding globulin ( SHBG ) , cortisol-binding globulin ( CBG ) , testosterone , free testosterone , dihydrotestosterone , and rostenedione , dihydroepi and rosterone sulfate ( DHEAS ) , and hydroxyprogesterone . The free and rogen index was also calculated . These variables were remeasured during the third week of OC intake and during the fourth and sixth cycles . There were no statistically significant differences in and rogenic variables among the four OCs . The DHEAS concentration decreased less with the 20 micrograms EE + desogestrel formulation compared with either 30 micrograms EE + desogesterel or norgestimate-containing formulations ( 20 % vs. 45 % ) . Concentrations of SHBG and CBG increased significantly in all four groups ( average 263 + /- 119 % and 94 + /- 26 % , respectively ) ; CBG increased less in women taking 20 micrograms EE + desogestrel ( about 75 % ) than in the other formulations ( about 100 % ) . The four modern , low-dose OCs tested had similar impacts on endogenous and rogen metabolism , yielding significant decreases in testosterone , dihydrotestosterone , and rostenedione , and DHEAS . All of these formulations may be beneficial in women with and rogen-related syndromes such as acne and hirsutism . Large studies are under way to establish which of the third-generation OCs is the least and rogenic . In vitro studies suggest that norgestimate has the least and rogenic profile Two triphasic oral contraceptives containing gestodene ( GES ) ( a new progestogen ) and levonorgestrel ( LNG ) were compared with respect to contraceptive effect , cycle control , acceptability and side effects . The serum concentrations of ingested hormones were measured together with ovarian , pituitary , and some adrenal hormones , as well as sex hormone binding globulin ( SHBG ) . The contraceptive effect and cycle control were good with both preparations , and there were only a few minor side effects . SHBG was elevated 2-fold in the LNG group and 3-fold in the GES group . The  GES concentration in serum varied more than the LNG concentration , but with correction for variations in SHBG binding , less variability in actual GES and LNG concentrations was seen . Serum levels of FSH , LH , estradiol and progesterone were all depressed with both preparations . The depression was more marked in the GES group , despite lower progestogen ingestion and similar serum concentrations . Equal decreases were found in testosterone , and rostenedione and dehydroepi and rosterone sulfate ( DHEA-S ) with both preparations Despite strong indirect evidence that and rogens stimulate prostate cancer development , data from most analytical studies on this association have been negative . To further investigate this issue , we studied the interrelationships between and rogenicity and insulin-like growth factor I ( IGF-I ) , insulin and leptin . Within a prospect i ve cohort study , we measured  testosterone , sex hormone-binding globulin ( SHBG ) and IGF-I , IGF-binding protein (IGFBP)-1 , IGFBP-3 , insulin and leptin , in plasma from 149 cases and 298 controls .  Testosterone correlated positively with SHBG , whereas testosterone and SHBG correlated inversely with IGF-I , IGFBP-3 , insulin , leptin and body mass index ( BMI ) . Indices of free testosterone showed an inverse linear correlation with leptin ( P<0.01 ) , and a strong drop in the 5th quintile of BMI . However , levels of free testosterone showed non-linear relationships over quintiles of insulin and IGF-I , with a significant increase in the second quintile of IGF-I compared with other levels . The absence of an association between plasma levels of  and rogens and prostate cancer risk in analytical studies , despite the strong indirect evidence of their tumour-stimulating effects , may reflect the complex and mostly inverse associations of and rogenicity to IGF-I , insulin and leptin which are hormones that have also been implicated as risk factors for prostate cancer Objective To compare the effects of tibolone and continuous combined hormone therapy on circulating sex steroids and their binding proteins and their relationship to  mammographic density .  Study design A prospect i ve , double-blind placebo-controlled study . A total of 166 postmenopausal women were equally r and omized to receive tibolone 2.5 mg , estradiol 2 mg/norethisterone acetate 1 mg ( E2/NETA ) or placebo . Serum analyses of sex steroids , insulin-like growth factor ( IGF-I ) and binding proteins and assessment of mammographic breast density were performed at baseline and after 6 months of treatment . Results Estrogens were markedly increased and and rogens decreased by E2/NETA . In contrast , tibolone had only a minor influence on circulating estrogens . Sex hormone binding globulin ( SHBG ) levels were reduced by 50 % , while levels of and rogens increased . Baseline values of estrone sulfate ( E1S ) , around 1.0–1.1 nmol/l , were increased to 44.7 nmol/l by E2/NETA and to only 1.7 nmol/l by tibolone ( p < 0.001 ) . Mammographic breast density displayed a negative correlation with age and body mass index and a positive association with SHBG . After 6 months there was also a negative correlation with levels of free testosterone . Conclusion We found that tibolone and E2/NETA caused distinct differences in estrogen/ and rogen status and blood levels of possible breast mitogens . The negative association between free testosterone and mammographic density could be a possible explanation for tibolone having less influence on the breast The hormonal and biochemical effects of danazol ( 600 mg a day ) and high-dose medroxyprogesterone acetate ( MPA ; 100 mg a day ) were studied in a  placebo-controlled , 6-month trial .  Serum gonadotrophins and prolactin levels did not change during danazol and MPA treatments , whereas oestradiol and progesterone levels decreased significantly in relation to placebo without any difference between danazol and MPA . Both drugs significantly suppressed the sex hormone-binding globulin level ( SHBG ) , and consequently , the free- and rogen index ( serum total testosterone nmol/l per SHBG nmol/l x 100 ) as compared with placebo , the effect of danazol being significantly stronger than that of MPA . Danazol , but not MPA , significantly increased serum aspartate aminotransferase ( ASAT ) , alanine aminotransferase ( ALAT ) and haemoglobin levels , and also thrombocyte counts , whereas MPA , but not danazol , increased the serum concentration of albumin in relation to placebo .  Serum total bilirubin , conjugated bilirubin , gamma-glutamyl transferase , creatinine , alkaline phosphatase , sodium and potassium levels and leucocyte counts remained unchanged during both treatments . Danazol and high-dose MPA did not differ from each other in their ovarian and anterior pituitary effects , while the increase in and rogenic activity induced by danazol was greater than that achieved with MPA . Danazol also had more biochemical effects than MPA . It interfered with the functions of the liver and the production of thrombocytes and haemoglobin , whereas MPA affected only albumin synthesis /release OBJECTIVE Excess weight has been associated with increased risk of cancer at several organ sites . In part , this effect may be modulated through alterations in the metabolism of sex steroids and IGF-I related peptides . The objectives of the study were to examine the association of body mass index ( BMI ) with circulating and rogens ( testosterone , and rostenedione and dehydroepi and rosterone sulfate ( DHEAS ) ) , estrogens ( estrone and estradiol ) , sex hormone-binding globulin ( SHBG ) , IGF-I and IGF-binding protein (IGFBP)-3 , and the relationship between sex steroids , IGF-I and IGFBP-3 . DESIGN AND METHODS A cross-sectional analysis was performed using  hormonal and question naire data of 620 healthy women ( 177 pre- and 443 post-menopausal ) . The laboratory measurements of the hormones of interest were available from two previous case-control studies on endogenous hormones and cancer risk . RESULTS In the pre-menopausal group , BMI was not related to and rogens and IGF-I. In the post-menopausal group , estrogens , testosterone and and rostenedione increased with increasing BMI . The association with IGF-I was non-linear , with the highest mean concentrations observed in women with BMI between 24 and 25 . In both pre- and post-menopausal subjects , IGFBP-3 did not vary across BMI categories and SHBG decreased with increasing BMI . As for the correlations between peptide and steroid hormones , in the post-menopausal group , IGF-I was positively related to and rogens , inversely correlated with SHBG , and not correlated with estrogens . In the pre-menopausal group , similar but weaker correlations between IGF-I and and rogens were observed . CONCLUSIONS These observations offer evidence that obesity may influence the levels of endogenous sex-steroid and IGF-related hormones in the circulation , especially after menopause . Circulating IGF-I , and rogens and SHBG appear to be related to each other in post-menopausal women The aim of the present study was to compare changes in the endogenous and rogen environment in healthy women while on low-dose oral contraceptives ( OCs ) . One-hundred healthy women were r and omized to receive one of four OCs during six months : 21 tablets of Cilest , Femodeen , Marvelon , or Mercilon . During the luteal phase of the pretreatment cycle , body weight and blood pressure were recorded and the following parameters were measured : sex hormone-binding globulin ( SHBG ) , corticosteroid-binding globulin ( CBG ) , testosterone ( T ) , free testosterone ( FT ) , 5 alpha-dihydrotestosterone ( DHT ) , and rostenedione ( A ) , dehydroepi and rosterone-sulphate ( DHEA-S ) and 17 alpha-hydroxyprogesterone ( 170HP ) while also the free and rogen index ( FAI ) was calculated . Measurements were repeated during the 3rd week of pill intake in the 4th and the 6th pill month . There were no differences on body mass and blood pressure with the use of the four OCs . The mean serum DHEA-S decreased significantly in all groups though less in the Mercilon group when compared to Cilest and Marvelon ( approximately 20 % vs 45 % ) . Mean serum SHBG and CBG increased significantly in all four groups approximately 250 % and 100 % , respectively . In each group CBG also increased significantly but less in women taking Mercilon ( -75 % ) as compared to the others ( -100 % ) . Current low-dose OCs were found to have similar impact on the endogenous and rogen metabolism with significant decreases of serum testosterone , DHT , A , and DHEA-S. They may be equally beneficial in women with and rogen related syndromes such as acne and hirsutism Anti and rogens or progestins with an anti and rogenic component usually have only a weak antigonadotropic activity . It is thus possible that the anti and rogenic effect on the cellular level is cancelled or at least reduced by an increased ovarian and rogen production . The aim of the four su bmi tted clinical studies of the progestin and anti and rogen dienogest alone ( 0.5 - 2 mg/day ) or of a combined regimen of ethinylestradiol ( 0.03 mg ) plus dienogest ( 2 mg ) ( EE/DNG ) was to examine the influence on the serum and rogen and SHBG concentrations as well as on the serum FSH , LH , progesterone and 17 beta-estradiol concentrations in young women . Like the progesterone derivatives , dienogest has a relatively low antigonadotropic activity . Inhibition of ovulation is mainly produced by peripheral mechanisms such as the reduction of preovulatory 17 beta-estradiol secretion .  Dienogest alone has no significant effects on the serum SHBG and and rogen concentrations . Unlike this , the combination of EE plus DNG markedly increases SHBG concentrations ( to 2.1 - 3.7 fold the basal levels ) . The decrease in serum and rogens with total testosterone ( by 17 and 40 % ) , free testosterone ( by 48 and 54 % ) and dehydroepi and rosterone sulfate ( by 51 % ) corresponds to the values shown in the literature for other oral contraceptives with modern progestins . EE/DNG does not affect the serum concentrations of 5 alpha-dihydrotestosterone ( DHT ) , although the marker of the peripheral transformation from T to DHT , and rostanediol glucuronide , is distinctly reduced ( by 38 % ) . In a double-blind comparison no differences are found between EE/DNG and a regimen combining 0.02 mg of ethinylestradiol and 0.150 mg of desogestrel . Solely the SHBG concentrations , with EE/DNG , as expected , are significantly higher . In a sequential regimen , dienogest , chlormadinone acetate and desogestrel ( progestins without binding to SHBG ) enhance the inhibitory effect of ethinylestradiol sulfonate on free testosterone , whereas norethindrone acetate and levonorgestrel ( progestins with a strong binding to SHBG ) reduce this effect of the estrogen significantly . These results exclude the possibility that the very distinct anti and rogenic effect of dienogest on a cellular level is neutralised or reduced by an increased systemic supply of and rogen OBJECTIVE In some women , a decline in sexual interest accompanies a relative and rogen insufficiency after menopause . We sought to characterize the hormonal effects of the combination of oral esterified estrogens and methyltestosterone and to investigate whether this regimen improves hypoactive sexual desire . DESIGN Double-blind r and omized trial . SETTING Healthy volunteers in a multicenter research environment . PATIENT(S ) Postmenopausal women taking estrogen therapy who were experiencing hypoactive sexual desire . INTERVENTION(S ) 4 months of treatment with 0.625 mg of esterified estrogens ( n = 111 ) or the combination of 0.625 mg of esterified estrogens and 1.25 mg of methyltestosterone ( n = 107 ) . MAIN OUTCOME MEASURES Baseline and end-of- study measurements of total and bioavailable testosterone and sex hormone-binding globulin ( SHBG ) , and mean change in level of sexual interest or desire as rated on the Sexual Interest Question naire . RESULT ( S ) Treatment with the combination of esterified estrogens and methyltestosterone significantly increased the concentration of bioavailable testosterone and suppressed SHBG . Scores measuring sexual interest or desire and frequency of desire increased from baseline with combination treatment and were significantly greater than those achieved with esterified estrogens alone . Treatment with the combination was well tolerated . CONCLUSION ( S ) Increased circulating levels of unbound testosterone and suppression of SHBG provide a plausible hormonal explanation for the significantly improved sexual functioning in women receiving the combination of esterified estrogen and methyltestosterone The effect of two oral contraceptive ( OC ) pills , both containing 150 micrograms of desogestrel , but with 20 ( Mercilon ) or 30 micrograms ( Marvelon/Desolett ) of ethinyl estradiol on plasma levels of lipids , lipoproteins and sex hormone binding globulin ( SHBG ) , total and free testosterone were compared in a double-blind , r and omized , two-center study in a total of 60 women over one year . A significant rise with Marvelon but not with Mercilon was seen in total cholesterol , HDL cholesterol , HDL-3 and apolipoprotein B , whereas LDL cholesterol decreased with Mercilon only . These effects result ed in significant differences between the two groups in the magnitude of responses in all these parameters except HDL-3 . HDL-2 , apolipoprotein A-1 and total phospholipids were elevated with both pills after treatment and with no difference in the degree of response between groups . The HDL/LDL cholesterol ratio tended to increase in both groups and that of apolipoproteins A-1/B in the women on Mercilon . Total triglycerides increased in both groups , but more in the women on Marvelon . Total testosterone decreased , particularly in the Marvelon group , whereas the two pills caused a similar increase in SHBG and decrease in free testosterone . It is concluded that the direction of changes in plasma lipids and lipoproteins with both these pills may as a whole be interpreted as beneficial , and that the differences in effect on LDL cholesterol and apolipoprotein B may suggest a slightly advantageous effect of Mercilon in this aspect . However , the clinical significance of these changes is uncertain . The results indicate a lack of and rogenicity of both pills
However , subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences : COCs containing second generation progestins and /or the lower estrogen doses ( 20–25 µg EE ) were found to have less impact on SHBG concentrations .
The current literature review and meta- analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations .
Due to the SHBG increase , free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T , but both affect SHBG .
BACKGROUND Combined oral contraceptives ( COCs ) reduce levels of and rogen , especially testosterone ( T ) , by inhibiting ovarian and adrenal and rogen synthesis and by increasing levels of sex hormone-binding globulin ( SHBG ) .
Although this suppressive effect has been investigated by numerous studies over many years , to our knowledge no systematic review concerning this issue had been performed .