Biomedical subjects

K Carlström

Publications and source records attributed to K Carlström.

At least 19 recordsLinked to original sources

PubMed2006

Gonadotrophin stimulation of non-luteinized granulosa cells increases steroid production and the expression of enzymes involved in estrogen and progesterone synthesis.

BACKGROUND: In regular IVF treatment, mature oocytes are collected with their luteinized granulosa cells (GCs). When in vitro maturation (IVM) of the oocytes is performed, non-luteinized GCs can be collected. We have investigated how these cells respond to gonadotrophin stimulation in culture. METHODS: GCs were collected from patients undergoing IVM treatment and compared with GCs from IVF patients. The cells were stimulated with FSH and/or hCG. After 48 h, culture media were collected for hormone analysis, and RNA was isolated for gene expression analysis. RESULTS: In IVM GCs, hCG and FSH alone and in combination induced significantly increased progesterone production, and FSH alone and in combination with hCG increased estrogen production. We also studied the gene expression of P-450aromatase and P-450scc and the receptors for FSH and LH. In non-luteinized GCs, the expression levels of P-450aromatase increased with all treatments, and P-450scc expression increased with the combined FSH and hCG treatment. LHR expression increased with FSH treatment, but the FSH receptor expression did not change with different treatments. CONCLUSIONS: Non-luteinized GCs behaved differently from luteinized GCs in culture. The data help understand the final stages of maturation of human oocytes and follicles.

Aromatase↗

PubMed2006

Are estrogen receptor content in breast cancer and effects of tamoxifen on sex hormone-binding globulin markers for individual estrogen sensitivity?

Individual women differ with respect to their sensitivity to estrogen and serum levels of sex hormone-binding globulin (SHBG) may reflect the individual response. We found a significant correlation between estrogen receptor (ER) concentrations in breast cancer tissue and SHBG levels during tamoxifen treatment. Estrogen sensitivity may be a general characteristic common to various organs and different between individual women.

Biomarkers, Tumor↗

PubMed2005

Treatment with percutanous testosterone gel in postmenopausal women with decreased libido--effects on sexuality and psychological general well-being.

OBJECTIVES: To elucidate if percutanous treatment with 10mg testosterone per day could enhance sexuality and psychological well-being in postmenopausal women presenting problems with low libido. Secondary to study the influence on blood lipids, hemoglobin and erythropoietin levels. METHODS: Fifty-three postmenopausal women participated. As a complement to their already on-going HRT, 10mg of a testosterone gel (Testogel, Besins-Iscovesco) or placebo was administered. Treatment continued for three plus three months in a double blind, randomized, crossover design. RESULTS: The scores concerning "frequency of sexual activity, orgasm and intercourse", "sexual arousal, fantasies and enjoyment", "satisfaction with orgasms", and "interest in sex" were all significally improved for testosterone addition as compared to placebo both before and after crossover. Testosterone levels increased more than 10-fold during treatment while DHT-levels were more than doubled. Estrogen levels were not affected during the addition of testosterone. Liver enzymes, total cholesterol, triglycerides, HDL and LDL revealed no significant differences between any of the periods or groups. Endometrial thickness did not change significantly during treatment. Hemoglobin and erythropoietin remained unchanged. No significant differences in the number of experienced side effects were found. CONCLUSION: Testosterone gel of 10mg had positive effects on several aspects of sexual life such as frequency of sexual activity, orgasm, arousal, fantasies and sexual interest in postmenopausal women on HRT. Several psychological variables were positively influenced. The given dose resulted in too high serum levels. Even if no negative effects were observed, monitoring of serum levels and a decreased dose should be considered in future studies.

Administration, Cutaneous↗

PubMed2005

Effects of combined estrogen/testosterone therapy on bone and body composition in oophorectomized women.

OBJECTIVE: To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen therapy on bone markers, bone mineral density and body composition in oophorectomized women. METHODS: Fifty women, 45-60 years old, who had undergone a hysterectomy and bilateral salpingo-oophorectomy for benign disorders, were randomly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily. Twenty-four weeks later, cross-over was performed to the other treatment regimen. Forty-four women completed the study. Their serum concentrations of insulin-like growth factor (IGF)-I, IGF binding protein (IGFBP)-3, osteocalcin, carboxyterminal telopeptide aminoterminal (ICTP), of type I collagen propeptide of type I procollagen (PICP) and interleukin (IL)-1 receptor antagonist were measured at baseline and after 24 weeks of both treatments, as were also their body mass index (BMI) and blood pressure. Bone mineral density of the total body, spine and hip and total body fat, total lean body mass, trunk fat and trunk lean mass were determined by dual-energy X-ray absorptiometry measurements at baseline and after 24 weeks of both regimens. RESULTS: During treatment, the addition of testosterone counteracted the decrease in IGF-I and PICP seen with estrogen therapy alone. Osteocalcin and ICTP were significantly reduced to the same extent by both therapies. No change ocurred in the IL-1 receptor antagonist. A significant increase was seen in total lean body mass with the estrogen/testosterone regimen, but the total fat mass, trunk lean or fat mass remained unchanged after 24 weeks of both treatments. No effect was detected on total, hip or spinal bone mineral density after treatment with estrogen alone or estrogen/testosterone. Likewise, BMI and blood pressure were unaffected. CONCLUSIONS: The addition of testosterone to oral estrogen might have positive effects on bone as suggested by the fact that it counteracted the decline in IGF-I and PICP levels. An anabolic effect on muscle was reflected by an increase in the total lean body mass. No adverse effects were noted on BMI, fat distribution or blood pressure during the 6-month treatment with oral testosterone undecanoate.

Body Composition↗

PubMed2004

Serum lipids in oophorectomized women during estrogen and testosterone replacement therapy.

OBJECTIVE: To evaluate the effects of giving testosterone undecanoate (TU) in addition to estrogen replacement on serum lipids in oophorectomized women. METHOD: Women with surgically induced menopause (n = 50) were randomly assigned to oral treatment with 2 mg of estradiol valerate in combination with 40 mg of TU or placebo for 24 weeks. The study was double-blind with cross-over to the other regimen for further 24 weeks of treatment. Forty-four women completed the study. Their serum concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, triglycerides, lipoprotein-(a) (Lp-(a)), total testosterone, estradiol and sex hormone-binding globulin (SHBG) were analyzed at baseline and after 24 weeks of each treatment. RESULTS: Serum levels of total testosterone increased markedly from a baseline mean of 0.8-4.9 nmol/l during testosterone addition. The levels of free testosterone significantly increased during the combined treatment and fell when given estrogen alone. Total and LDL-cholesterol levels were significantly reduced by both treatments as also were those of Lp-(a) although the difference was not significant. We found a 13% reduction in HDL-cholesterol levels when testosterone was added, but no change with estrogen alone. Triglyceride levels were increased by estrogen treatment, but not affected by the combination of estrogen plus testosterone. CONCLUSIONS: These findings suggest that 40 mg of TU can be given in addition to estrogen replacement with only little side-effects on the pattern of circulating lipids. Although supraphysiological concentrations of testosterone were induced a significant reduction in total and LDL-cholesterol levels occurred.

Cross-Over Studies↗

PubMed2004

Circulating concentrations of hemostatic factors and two "steroid sensitive proteins" during oral hormone replacement therapy in women with coronary heart disease.

OBJECTIVE: To study a possible use of sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) as markers for changes in hemostatic factors during oral postmenopausal hormone replacement therapy (HRT). METHODS: Twenty-eight postmenopausal women were treated with oral conjugated equine estrogens+oral medroxyprogesterone acetate (CEE + MPA, n = 15) or with placebo (n = 13). Serum SHBG, CBG, testosterone, cortisol and plasma coagulation factors, coagulation inhibitors and markers of coagulation activation were measured before and after 6 and 12 months of treatment. RESULTS: Pretreatment plasminogen activator inhibitor 1 (PAI-1) levels correlated negatively to SHBG and antithrombin III (AT III) negatively to total and free cortisol. In the CEE + MPA group, CBG, SHBG and Factor VII increased, and PAI-1, AT III and free testosterone decreased during treatment. No significant changes were found in plasma von Willebrand factor antigen, thrombin-antithrombin complex, fibrin D-dimer and fibrinogen. A significant, negative correlation was found between changes in SHBG and PAI-1. No changes were found in the placebo group. CONCLUSION: The only correlation found between changes in "steroid sensitive" proteins and hemostatic factors was between increased SHBG and a possibly beneficial effect of estrogens, i.e. decreased PAI-1 values. SHBG or CBG could not be used as predictors of increased cardiovascular risk during postmenopausal oral HRT.

Administration, Oral↗

PubMed2004

A comparative study of breast cell proliferation during hormone replacement therapy: effects of tibolon and continuous combined estrogen-progestogen treatment.

OBJECTIVE: To use the fine-needle aspiration (FNA) biopsy technique to compare the effects of tibolone, conventional hormone replacement therapy (HRT) and placebo on breast cell proliferation in postmenopausal women. METHODS: A total of 91 women were randomized to receive either estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA), tibolone 2.5 mg or placebo for 6 months in a prospective double-blind trial. Breast cell proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody. RESULTS: From the 83 women who completed the study, a total of 166 FNA biopsies were obtained, and 118 of these aspirates (71%) were evaluable for MIB-1 content. Women with assessable biopsies were younger, had a lower body mass index, and had higher levels of sex hormone binding globulin and insulin-like growth factor-I than women in whom the cell yield was insufficient. During treatment with E2/NETA, there was an increase in proliferation (percentage of MIB-1) from a mean value of 2.2 to 6.4% after 6 months (p < 0.01). No significant changes were recorded during treatment with tibolone or placebo. There was a negative association between proliferation and serum levels of total (r(s) = -0.29, p < 0.05) and free (rs = -0.31, p < 0.03) testosterone. CONCLUSIONS: Tibolone seems to have little influence on breast cell proliferation.

Aged↗

PubMed2004

Tamoxifen and megestrol acetate for postmenopausal breast cancer: diverging effects on liver proteins, androgens, and glucocorticoids.

AIM: To compare the effects of tamoxifen and megestrol acetate on liver proteins, androgens, and glucocorticoids during adjuvant treatment for postmenopausal breast cancer. METHODS: A subgroup of women within a large prospective multicenter trial were followed with blood sampling every 3 mo during 2 yr. Women were randomized to receive either continuous tamoxifen 40 mg/d or repeated sequential treatment with tamoxifen and megestrol acetate (MA) 160 mg/d. RESULTS: We found profound and distinct differences between the two regimens. Tamoxifen increased steroid-binding proteins (SHBG and CBG) and suppressed circulating androgens and IGF-I. In contrast, the metabolic effects of tamoxifen were clearly antagonized by MA. There was a rise in IGF-I and marked suppression of steroid-binding proteins. Levels of free testosterone were reduced by 70%. MA also caused apparent adrenal suppression. CONCLUSION: The different effects on anabolic/catabolic balance and adrenal function may relate to certain clinical effects during treatment.

Aged↗

PubMed2003

Breast cell proliferation in postmenopausal women during HRT evaluated through fine needle aspiration cytology.

The basis of breast cancer risk associated with hormonal therapies may lie in the regulation of cell proliferation. In a prospective, double-blind, randomized study postmenopausal women were given continuous combined hormone replacement therapy (HRT) either as estradiol valerate 2 mg/dienogest 2 mg, (E2V/DNG) or estradiol 2 mg/noretisterone acetate 1 mg (E2/NETA) for 6 months. Fine needle aspiration (FNA) biopsies were used for immunocytochemical analysis of breast cell proliferation before and during treatment. From 45 women completing the study 135 biopsies were obtained. In the total material there was a more than 4-fold increase in proliferation between baseline and 3 months (p < 0.001). The mean percentage of MIB-1 positive breast cells increased from 2.2 to 9.1%. In some individual women values were as high as 25%. No further increase was recorded at 6 months. While numerical values were somewhat lower in the E2V/DNG group, there were no significant differences between treatments. There was a positive correlation between breast cell proliferation (MIB-1%) and circulating levels of both estradiol (r(s) = 0.54, p < 0.01) and estrone (r(s) = 0.53, p < 0.01) after 3 and 6 months of treatment. No correlations with other endogenous hormones, proteins or with the two exogenous progestogens dienogest and norethisterone were observed. Increased breast cell proliferation should probably be regarded as an unwanted side-effect during HRT. Means to identify those women with the most pronounced proliferative response should be developed. The FNA biopsy technique may be a useful tool to monitor and evaluate the proliferative response to HRT in the normal breasts of postmenopausal women.

Biopsy, Needle↗

PubMed2003

Hormone receptor status in breast cancer--a comparison between surgical specimens and fine needle aspiration biopsies.

The present study was performed to evaluate the immunocytochemical analysis (ICA) of oestrogen (ER) and progesterone receptor (PR) in fine needle aspiration (FNA) biopsies from primary breast cancers as compared with the established enzyme immunoassays (ER-EIA and PR-EIA) based on cytosol homogenates from the corresponding resected tumour specimens. A total of 967 primary breast cancers were assessed for ER and PR content by both methods. Correlations between EIA and ICA expressed as percentage of tumour cells with a positive staining were highly significant (P < 0.001) for ER and PR. Staining intensity yielded only limited additional information. The concordance between the two techniques was about 80%. Evaluation of biological parameters by FNA may be useful to decide the optimal treatment for breast cancer patients.

Adult↗

PubMed2003

Maternal and gestational correlates of pregnancy prolactin and growth hormone in USA and China.

The objective of this study is to determine correlates of prolactin and growth hormone levels among pregnant women in the USA and China. We studied 304 pregnant Caucasian and 335 pregnant Chinese women. Levels of prolactin and growth hormone were measured at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Both growth hormone and, to a lesser extent, prolactin were inversely associated with pregnancy weight and body mass index, history of a previous live birth and newborn size, whereas educated women had higher levels of both hormones. Growth hormone levels were lower in women who gained more weight, smoked and had nausea and vomiting during pregnancy, whereas prolactin increased with longer total gestation. We found robust associations between maternal and newborn characteristics on the one hand and prolactin and growth hormone during pregnancy on the other.

Adult↗

PubMed2002

Diurnal rhythm and effects of oral contraceptives on serum dehydroepiandrosterone sulfate (DHEAS) are related to alterations in serum albumin rather than to changes in adrenocortical steroid secretion.

Dehydroepiandrosterone sulfate (DHEAS), which is of almost exclusive adrenal origin, is important for the androgen status in women and prepubertal children, and DHEAS assays are used in the investigation of hyperandrogenism. There are conflicting reports concerning a diurnal variation in serum DHEAS. Although of adrenocortical origin, serum DHEAS levels are decreased by oral contraceptives (OCs). DHEAS is strongly bound to serum albumin and has a very low metabolic clearance rate. The present study was performed in order to investigate whether a diurnal variation in serum DHEAS exists and, if so, whether this diurnal variation and the decreased DHEAS levels following OC use are related to alterations in adrenocortical steroids or to changes in serum albumin. Serum concentrations of DHEAS, dehydroepiandrosterone (DHEA), cortisol and albumin were determined in blood samples taken every half hour over a 24-h period in 10 healthy women before and during use of combined OCs. Significant and frequently synchronous diurnal variations in serum DHEAS and albumin were found before as well as during OC use. These variations were not synchronous with the diurnal variation in DHEA. OCs significantly decreased serum DHEAS and albumin levels. A multiple regression analysis showed changes in albumin to be the most decisive factor for the diurnal variation as and for OC-induced changes in DHEAS. Changes in serum DHEAS during the day and following OC use are related to alterations in its main binding protein, serum albumin, rather than to changes in adrenocortical steroid secretion.

Adult↗

PubMed2002

Bioavailable testosterone in men with rheumatoid arthritis-high frequency of hypogonadism.

OBJECTIVES: To study bioavailable testosterone (T) in men with rheumatoid arthritis (RA) by determining non-sex hormone-binding globulin (SHBG)-bound T (NST) under standardized conditions and to investigate if NST is related to disease variables. METHODS: Basal serum concentrations of total T, SHBG and luteinizing hormone (LH) were measured in 104 men with RA, and the levels of NST as well as the quotient T/SHBG were calculated. The data were compared with those of 99 age-matched healthy men. The results were analysed separately for the age groups 30-49, 50-59 and 60-69 yr. RESULTS: The RA men had lower NST levels than the healthy men in all age groups. T levels and the T/SHBG ratio were lower only in the age group 50-59 yr. SHBG did not differ significantly. LH was significantly lower in the patients than in the controls. Thirty-three of the 104 patients were considered to have hypogonadism compared with seven of the 99 healthy men. The only clinical variable apart from age that had a significant impact on NST was the Stanford Health Assessment Questionnaire (HAQ). CONCLUSION: Men with RA had lower levels of bioavailable T and a large proportion were considered hypogonadal. The low levels of LH suggested a central origin of the relative hypoandrogenicity.

Adult↗

PubMed2002

Correlates of pregnancy oestrogen, progesterone and sex hormone-binding globulin in the USA and China.

The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormone-binding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics.

Adult↗

PubMed2002

Ovarian ultrasound and ovarian and adrenal hormones before and after treatment for hyperthyroidism.

OBJECTIVE: To relate thyroid, steroid and pituitary hormones to ovarian ultrasonographic findings in hyperthyroid patients before and during treatment. STUDY DESIGN: Ultrasonography of the ovaries and serum hormone determination by immunoassay were performed before and during thiamazole therapy in 18 women of fertile age treated for hyperthyroidism at the Danderyd Hospital from 1996 to 1998. RESULTS: When hyperthyreotic, the patients had elevated serum levels of sex hormone-binding globulin (SHBG) and subnormal values of cortisol, free testosterone (fT) and dehydroepiandrosterone (DHEA). In the euthyreotic state following treatment, endocrine variables were normalized. Patients with a short duration of the disease had higher pretreatment levels of free thyroxine (fT4), SHBG and testosterone and lower corticosteroid binding globulin (CBG) and cortisol levels compared to patients with a long duration of the disease. The pretreatment ultrasonographic picture was abnormal in 16 of 18 patients. Of the 8 patients who were examined by ultrasonography after 3 months of treatment, all but 1 showed a normal picture. Samples from patients showing an abnormal ultrasonographic picture had significantly higher fT4 and lower free testosterone (fT) values than samples from patients with a normal ultrasonographic picture. CONCLUSION: Ultrasonographic findings showing a multicystic/multifollicular picture, resembling polycystic ovaries (PCO), in hyperthyroidism may be related to direct effects of thyroid hormones on the ovaries and/or altered intraovarian androgen environment due to elevated SHBG levels. It is highly recommended to assess the thyroid status in patients with multicystic/multifollicular ovaries/PCO.

Adrenal Cortex Hormones↗

PubMed2002

Addition of testosterone to estrogen replacement therapy in oophorectomized women: effects on sexuality and well-being.

OBJECTIVE: To evaluate the effect of adding testosterone undecanoate 40 mg daily to estrogen replacement on sexual function, psychological well-being and self-esteem in surgically postmenopausal women. METHODS: A letter of invitation to participate in the study was mailed to women who had undergone hysterectomy and bilateral oophorectomy for benign disorders during 1990-98. Fifty women, 45-60 years old, were consecutively recruited and randomly assigned to oral treatment with testosterone undecanoate 40 mg plus estradiol valerate 2 mg daily or placebo plus estradiol valerate 2 mg daily for 24 weeks. A double-blind design was chosen, with cross-over to the other regimen for another 24 weeks of treatment. Forty-four women completed the study. Outcome included scores on McCoy's sex scale questionnaire, the Psychological General Well-Being index and a self-esteem questionnaire, at baseline and after 24 weeks of either treatment. Serum concentrations of total testosterone, sex hormone binding globulin, free testosterone, dihydrotestosterone, androstenedione, estradiol, follicle stimulating hormone and luteinizing hormone were analyzed at baseline and after 24 weeks of both treatment regimens. RESULTS: After 24 weeks, both treatment regimens had significantly improved some of the sexual variables. The addition of testosterone had a significantly better effect on the sex variables 'enjoyment of sex', 'satisfaction with frequency of sexual activity' and 'interest in sex'. The total McCoy score was significantly increased by both treatments, but there was a stronger effect when testosterone was also given. Although both regimens improved psychological well-being and self-esteem, we found no significant differences between testosterone-estrogen or estrogen alone at 24 weeks. Serum levels of all androgens, with considerable individual variation, increased significantly from baseline after 24 weeks of testosterone-estrogen treatment. Supraphysiological levels were achieved in a significant proportion of the women. Increases in estradiol and sex hormone binding globulin were less marked when testosterone was also given. Both treatments reduced gonadotropin levels. CONCLUSIONS: The addition of testosterone undecanoate improved specific aspects of sexual function more than treatment with estrogen alone. Improvements in well-being and self-esteem were similar for both treatments. If testosterone undecanoate 40 mg daily should be used for clinical treatment, regular monitoring of androgen serum levels is needed.

Cross-Over Studies↗

PubMed2001

Interleukin 1beta, interleukin-6, and tumor necrosis factor-alpha in endometriotic tissue and in endometrium.

OBJECTIVE: To compare the levels of IL-1beta, IL-6, and TNFalpha in endometriotic tissue and in endometrium from women with endometriosis and healthy controls. DESIGN: Open. SETTING: Department of Obstetrics and Gynecology at a university hospital. PATIENT(S): Twenty-six women with endometriosis and 22 controls operated on for clinical indications. INTERVENTION(S): ELISA in homogenized tissue samples collected during surgery. MAIN OUTCOME MEASURE(S): Levels of IL-1beta, IL-6, and TNFalpha in tissue homogenates. RESULT(S): The three types of tissue differed significantly with respect to all three cytokines. Endometriotic tissue had significantly higher concentrations of IL-1beta than endometrium from both patients with endometriosis and healthy controls. Both endometriotic tissue and endometrium from patients had significantly higher concentrations of IL-6, and endometriotic tissue had significantly lower concentration of TNFalpha than did endometrium from controls. IL-1beta showed a cycle phase dependence that was significant in endometrium from patients, being higher in the secretory than in the follicular phase. IL-1beta was significantly higher in endometrioma than in lesions of other localizations. Concentrations of IL-1beta and IL-6 were positively correlated in endometriotic tissue and in endometrium from controls. No other significant correlations were found. CONCLUSION(S): This study has shown a significant production of IL-1beta, IL-6, and TNFalpha in endometriotic tissue and endometrium, with significant differences between the tissue types, indicating a deviating cytokine pattern in both endometriotic tissue and endometrium from women with endometriosis compared with that from healthy controls.

Endometriosis↗

PubMed2001

Effects of oral contraceptives on breast epithelial proliferation.

The association between oral contraceptive (OC) use and breast cancer is not fully understood. Estrogen is a known mitogen to breast epithelial cells, but there is still a controversy about the effect of added progestogens. Fine needle aspiration (FNA) biopsies were used to assess epithelial proliferation in normal breast tissue from 106 healthy premenopausal women with and without oral contraceptives. In 26 women biopsies were performed before and after 2 months of OC use. Proliferation, expressed as percentage of Ki-67/MIB-1 positive cells, was correlated to endogenous progesterone, androgenic/anabolic compounds and exogenous progestogen. We found a higher proliferation (p = 0.03) in OC users compared to non users, with mean values of 4.8% and 2.2%, respectively. There was a positive correlation between proliferation and progesterone levels in non-users and with serum levonorgestrel concentrations in women using OCs containing this progestogen (rs = 0.43, p = 0.02). Women using OCs had significantly lower serum androgen levels compared to naturally cycling women and free testosterone levels displayed an inverse relation to breast epithelial proliferation. There was a marked variation in the response to exogenous sex steroids. In certain women after 2 months of OC use, the percentage of MIB-1 positive cells was as high as 40-50%. The results add to the growing evidence that progestogens may be mitogenic in breast tissue. Increased proliferation during hormonal contraception should be regarded as an unwanted and potentially hazardous side effect. Efforts should be made to define hormonal contraceptive regimens which minimize breast epithelial proliferation and to identify those women with the most pronounced proliferative response.

Adolescent↗