Changes in serum concentrations of growth hormone, insulin, insulin- like growth factor and insulin-like growth factor-binding proteins 1 and 3 and urinary growth hormone excretion during the menstrual cycle

Few studies exist on the physiological changes in the concentrations of growth hormone (GH), insulin-like growth factors (IGF) and IGF-binding proteins (IGFBP) within the menstrual cycle, and some controversy remains. We therefore decided to study the impact of endogenous sex steroids on the GH-IGF-IGFBP axis during the ovulatory menstrual cycle in 10 healthy women (aged 18-40 years). Blood sampling and urinary collection was performed every morning at 0800 h for 32 consecutive days. Every second day the subjects were fasted overnight before blood sampling. Follicle stimulating hormone, luteinizing hormone (LH), oestradiol, progesterone, IGF-I, IGFBP-3, sex hormone-binding globulin, dihydroepiandrosterone sulphate and GH were determined in all samples, whereas insulin and IGFBP-1 were determined in fasted samples only. Serum IGF-I concentrations showed some fluctuation during the menstrual cycle, with significantly higher values in the luteal phase compared to the proliferative phase (P < 0.001). Mean individual variation in IGF-I concentrations throughout the menstrual cycle was 13.2% (SD 4.3; range 0.1-18.3%). There were no cyclic changes in IGFBP-3 serum concentrations and no differences in IGFBP-3 concentrations between the luteal and the proliferative phases. Mean individual variation in IGFBP- 3 concentrations throughout the menstrual cycle was 8.8% (SD 2.7; range 3.2-14.1). IGFBP-1 concentrations were inversely associated with insulin concentrations, and showed a significant pre-ovulatory increase that returned to baseline at the day of the LH surge. Fasting insulin concentrations showed large fluctuations throughout the menstrual cycle without any distinct cyclic pattern. No cyclic changes in urinary GH excretion during menstrual cycle were detected. We conclude that, although IGF-I concentrations are dependent on the phase of the menstrual cycle, the variation in IGF-I concentrations throughout the menstrual cycle is relatively small. Therefore, the menstrual cycle does not need to be considered when evaluating IGF-I or IGFBP-3 serum values in women suspected to have GH deficiency.      

Effects of sex, phase of the menstrual cycle and gonadal hormones on pain in healthy humans

Sex differences in pain have been noted; women typically report more pain than men. Gonadal hormones may influence pain reports, and, moreover, such hormones may help to explain sex differences and menstrual cycle differences in pain. This study measured venipuncture and intravenous catherization pain during the follicular and luteal phases of the menstrual cycle in regularly menstruating women. Pain was also assessed in a group of men. Pain ratings were higher in women than men. In women, pain ratings did not differ between the follicular and luteal phases. Estradiol and progesterone increased from follicular to luteal phases. Within-phase analyses revealed that pain ratings were positively correlated with estradiol and progesterone during the luteal phase. Moreover, increases in estradiol and progesterone across the menstrual cycle were positively correlated with increases in pain. These findings suggest that variations in gonadal hormones during the menstrual cycle influence the experience of pain in healthy women.     

Sex steroid hormones and circulating IgE levels.

The possible influence of sex steroid hormones on circulating IgE levels in general and IgE anti-Candida antibodies in particular was studied by quantification of plasma levels of progesterone, estradiol and IgE (total and anti-Candida-specific) in females during the follicular and luteal phases of the menstrual cycle, and during pregnancy. IgE levels during the follicular and luteal phases were not significantly different, although the mean values for the luteal phase were slightly lower. This trend was apparent in daily samples from two normal females during one menstrual cycle. During pregnancy, when the levels of circulating sex steroids were high, IgE levels were only slightly higher than in the follicular and luteal phases. In men and in gonadal dysgenetics, circulating progesterone levels were similar to those of women during the follicular phase (i.e., lower than in the luteal phase or in pregnancy), but the IgE levels were not different. The apparently low levels of IgE during the luteal phase may therefore be due to physiological factors other than fluctuations in the sex steroid hormones. From the present studies, it is apparent that sex steroid hormones have little or no effect on humoral IgE levels, in marked contrast to previously described correlations for other immunoglobulins, especially anti-Candida antibodies.     

Strength training effects on urinary steroid profile across the menstrual cycle in healthy women

Some studies suggest that performing strength training may cause alterations on the hypothalamic pituitary axis, resulting in steroid hormone variations. Intense training has been associated to slow the concentrations of estrogens and progesterone in women. The main purpose of this study was to evaluate the effects of strength training on the urinary steroid concentrations across the menstrual cycle phases. Twenty healthy women, regularly menstruating and not using pharmacologic contraceptives, performed a strength training during 8 weeks. Participants worked out 3 sets × 10 repetitions, with 2 min recovery time between sets, at 70–75 % of one maximum strength repetition. Urine samples were taken in three different phases of the menstrual cycle (menstrual, follicular and luteal) and they were collected both before and after training. Testosterone, DHEA, cortisol, cortisone, estradiol and progesterone concentrations were determined by gas chromatography-mass spectrometry. The results showed a significant decline after training in the urinary excretion of estradiol, during the menstrual and follicular phase, and progesterone, during the menstrual and luteal phase. No significant difference was observed for other steroid hormones. These data demonstrated that strength training can play an important role in the estrogen and progesterone metabolism in women, decreasing their levels across the menstrual cycle.     

Morphometric analysis of fibroblasts of the mammary lobular stroma during the follicular and luteal phases of the menstrual cycle

We determined the nuclear volume of fibroblasts of the normal mammary lobular stroma during the follicular and luteal phases of the menstrual cycle. Twenty patients aged 15 to 35 years and eumenorrheic for at least 6 months were randomly assigned to 2 groups, i.e., 10 women in the follicular phase and 10 in the luteal phase. The nuclear volume was 34.4 micron 3 and 98.8 micron 3 for the follicular and luteal phases, respectively, with the difference being statistically significant (p < 0.05). These data suggest a higher metabolic activity in the mammary intralobular stroma during the luteal phase of the menstrual cycle, probably due to a synergistic action of estradiol and progesterone.     

Plasma leptin levels in obese and non-obese postmenopausal women before and after hormone replacement therapy

Objective: the aim of this study was to investigate the effect of hormone replacement therapy (HRT) on plasma leptin levels in postmenopausal women, and the relationship between the plasma leptin levels and obesity. Methods: premenopausal women with normal cycles (n=30; mean ages, 35.4±8.3 years) and postmenopausal women (n=45; mean ages, 49.5±4.7 years) were randomly selected. Women were classified as obese (BMI>27 kg/m²) and as non-obese (BMI<27 kg/m²). Blood samples were obtained from the premenopausal women at the beginning of cycle, and from the postmenopausal women before and 6 months after HRT. Plasma leptin levels were measured by radioimmunassay. Results: plasma leptin levels were significantly higher in premenopausal women than in postmenopausal women (18.60±5.0; 3.67±2.44 ng/ml, respectively, P<0.001). Obese premenopausal women (n=15) had significantly higher plasma leptin levels (24. 60±7.81 ng/ml) in comparison with the levels of the non-obese premenopausal women (n=15; 12.50±4. 63 ng/ml) (P<0.001). Although there was no significant difference in the plasma leptin levels between obese (n=25) and non-obese (n=20) postmenopausal women before HRT, plasma leptin levels were significantly elevated in both obese and non-obese postmenopausal women after HRT (P<0.001), and the obese women had significantly higher plasma leptin levels than the non-obese (29.05±10.53; 14.78±6.76 ng/ml, respectively, P<0.001). Conclusion: HRT is effective in the elevation of the plasma leptin levels in postmenopausal women, and in obese women the increase of the plasma leptin levels are more marked than the non-obese women after HRT.     

Modification of serum IGF-I,IGFBPs and SHBG levels by different HRT regimens

During the menopause, levels of SHBG, IGF-I and IGFBPs are significantly modified by the use of different HRT regimens. Objective: The aim of this study is to evaluate the influence of three different HRT regimens on serum levels of SHBG, IGF-I, IGFBP-1 and IGFBP-3 in postmenopausal women. Methods: 41 postmenopausal women requesting HRT were enrolled in the study. Subjects were divided in three groups according to the therapy assigned; Group A: estradiol 2 mg/day+cyproterone acetate 1 mg/day in a cyclic sequential regimen; Group B: estradiol hemihydrate 2 mg/day plus norethisterone acetate (NETA) 1 mg/day in a continuous combined regimen; Group C: estradiol hemihydrate 1 mg/day plus NETA 0.5 mg/day in a continuous combined regimen. Blood samples were drawn before the start of hormonal treatment and after 6 months of HRT. Levels of SHBG, IGF-I, IGFBP-1 and IGFBP-3 in the serum were measured by means of a specific immunoassay. Results: In group A, a significant increase of SHBG, no change of IGFBPs and a significant decrease of IGF-I were observed; in group B and in group C, no significant variations for any of the parameters were recorded. Conclusions: The association of cyproterone acetate to oral estradiol determines a significant reduction of IGF-I levels and an increase of SHBG; nevertheless, it does not seem to influence the serum levels of the IGF-I binding proteins. The treatment with oral continuous combined estrogens plus androgenic progestins, at low doses, produces minor, not significant, changes in the circulating levels of IGF-I, SHBG and IGFBPs.     

Increased (E)-4-hydroxy-2-nonenal and asymmetric dimethylarginine concentrations and decreased nitric oxide concentrations in the plasma of patients with major depression

Background: (E)-4-Hydroxy-2-nonenal (HNE) is a highly electrophilic end-product of lipid peroxidation. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide synthase (NOS). ADMA is metabolised by dimethylarginine dimethylaminohydrolase (DDAH). DDAH contains a nucleophilic cysteine residue in its active site. There is an increase in lipid peroxidation in major depression. Major depression is associated with the development of coronary heart disease (CHD) and greatly increases morbidity and mortality. There is an increase in circulating ADMA in CHD and vascular risk factors. Objectives: To determine plasma HNE, ADME and nitric oxide (NO) concentrations in patients with major depression compared to normal volunteers and to examine the effect of HNE on ADMA formation and DDAH activity in cultured endothelial cells. Methods: The study was conducted in 25 patients with major depression (DSM-IV criteria) and 25 healthy control subjects. Plasma concentrations of HNE were determined as the O-pentafluorylbenzyl oxime using capillary column GC–MS and deuterated HNE as the internal standard; ADME by LC–MS–MS using ¹³C⁶- -arginine as the internal standard; and NO by GC–MS following reduction to nitrate and nitrite and derivatisation to the pentafluorobenzyl derivative using [¹⁵N]nitrate and [¹⁵N]nitrite as the internal standards. Human umbilical vein endothelial cells were incubated in serum-free medium in the presence of HNE. The concentration of ADMA in the medium was determined by LC–MS–MS. DDAH activity was determined by measuring -citrulline in endothelial cell lysates using LC–MS. Results: There was a significant increase in the plasma concentration of HNE (P<0.0001) and ADMA (P<0.0002) in patients with major depression. There was a significant decrease in the plasma concentration of NO (P<0.0001). A significant positive correlation was found between the plasma concentrations of HNE and ADMA (r=0.63, P<0.0001). A significant negative correlation was detected between the plasma concentrations of ADMA and NO (r=−0.595, P<0.0001). HNE significantly increased ADMA formation (P<0.0001) and significantly decreased DDAH activity (P<0.0001) in cultured endothelial cells. The effects of HNE on DDAH activity were significantly attenuated by the addition of glutathione (P<0.0001). Limitations: No allowance was made for the phase of the menstrual cycle which could influence plasma nitric oxide concentrations. Conclusions: There is an increase in circulating HNE in major depression. HNE inactivates the cysteine residue in the active site of endothelial DDAH leading to the accumulation of ADMA in the circulation. The ADMA then decreases the production of eNOS. This could reduce the amount of NO diffusing from cerebral blood vessels to nearby neurons and influence the release of neurotransmitters. ADMA also constricts cerebral blood vessels and may contribute to the decreased regional perfusion in major depression. The accumulation of ADMA could explain the increased risk of CHD in major depression. The preservation of DDAH activity and the reduction of ADMA accumulation may represent a novel therapeutic approach to the treatment of major depression.     

A comparison of the central effects of different progestins used in hormone replacement therapy

Objective: To evaluate the central effect exerted by different progestins used for hormone replacement therapy. Methods: Randomised, placebo-controlled study. One hundred-twenty postmenopausal women on continuous hormonal replacement therapy with transdermal estradiol (50 μg per day) associated, for 10 days every 28 days, with four different progestins: dydrogesterone (DYD; 10 mg per day; n=20), medroxyprogesterone acetete (MPA; 10 mg per day; n=20), nomegestrol acetate (NMG; 5 mg per day; n=20) or norethisterone acetate (NETA; 10 mg per day; n=20). Other 40 women, 10 for each treatment group, were used as controls and were monitored for a single cycle of 28 days during the administration of transdermal estradiol plus placebo. Morning basal body temperature (BBT) was monitored for 28 days. Anxiety, by the state-trait anxiety inventory, and depression, by the self-evaluation depression scale of Zung, were evaluated just prior to and in the last 2 days of the 10-day progestins adjunct. Results: All progestins except DYD increased (P<0.0001) BBT by 0.3–0.5 °C. Anxiety was decreased by DYD (−2.3+1.1; P<0.01) and MPA (−1.5+0.5; P<0.01), but not by NMG or NETA. Depression did not significantly increase during progestins and actually decreased during MPA (−3.0+0.7; P<0.01). Only the effect of DYD on anxiety and that of MPA on depression were significant versus the control group (P<0.05). Conclusions: Different progestins exert different central effects. DYD has the peculiarity of not increasing BBT and of decreasing anxiety, which is also decreased by MPA. Depression is not negatively affected by the tested progestins and it may be ameliorated by MPA. The present data may help to individualise the progestin choice of hormone replacement therapy.     

Changes in peak expiratory flow and respiratory strength during the menstrual cycle

This study evaluated the spirometry and respiratory static pressures in 17 young women, twice a week for three successive ovulatory menstrual cycles to determine if such variables changed across the menstrual, follicular, periovulatory, early-to-mid luteal and late luteal phases. The factors phases of menstrual cycle and individual cycles had no significant effect on the spirometry variables except for peak expiratory flow (PEF) and respiratory static pressures. Significant weak positive correlations were found between the progesterone:estradiol ratio and PEF and between estrogen and tidal volume (r = 0.37), inspiratory time (r = 0.22), expiratory time (r = 0.19), maximal inspiratory pressure (r = 0.25) and maximal expiratory pressure (r = 0.20) and for progesterone and maximal inspiratory pressure (r = 0.32) during the early-to-mid luteal phase. Although most parameters of the spirometry results did not change during the menstrual cycle, the correlations observed between sexual hormones and respiratory control variables suggest a positive influence of sexual female hormones controlling the thoracic pump muscles in the luteal phase.     

Positive effects on cardiovascular and breast metabolic markers of oral estradiol and dydrogesterone in comparison with transdermal estradiol and norethisterone acetate

Objectives: To assess differences in two sequential combined hormone replacement therapy (HRT) products on selected cardiovascular and breast metabolic markers. The products were different concerning the route of administration of estradiol and its combined progestin, either oral or transdermal, and the androgenic properties of progestogens, respectively, dydrogesterone and norethisterone acetate. Methods: One hundred and nineteen healthy non-hysterectomized postmenopausal women were included in this open, multi-center, two parallel group trial. They were randomized to a treatment of six 28-day cycles with oral estradiol sequentially combined with dydrogesterone (oE2/D10) or a sequential combination patch of estradiol plus norethisterone acetate (tdE/NETA). At baseline and after six cycles the high-density lipoprotein cholesterol (HDL-C), the sex hormone binding globulin (SHBG) and the total insulin-like growth factor-I (IGF-I) blood levels were determined by a central laboratory. A total of 89 women were compliant to the protocol. Results: After six cycles, a statistically significant difference (P<0.001) concerning HDL-C, SHBG and IGF-I levels was found between the two treatment groups. The HDL-C levels were increased in the oE2/D10 group and decreased in the tdE/NETA group, with a final difference of about 0.3 mmol/l. The oE2/D10 treatment induced a sharp increase (about 57 mmol/l) in SHBG levels. IGF-I levels decreased with both the products, but the difference in favor of the oE2/D10 treatment was of about 30 ng/ml. Moreover, patients on tdE/NETA with an IGF-I baseline value below the median showed an increase. Conclusion: Oral estradiol sequentially combined with dydrogesterone, a non-androgenic progestogen, induced positive changes of some cardiovascular (HDL-C) and breast (SHBG and IGF-I) metabolic markers. These effects were significantly different from those obtained with a transdermal estradiol associated to an androgenic progestogen.     

Comparison of follicular fluid IGF-I, IGF-II, IGFBP-3, IGFBP-4 and PAPP-A concentrations and their ratios between GnRH agonist and GnRH antagonist protocols for controlled ovarian stimulation in IVF-embryo transfer patients

BACKGROUND: Insulin-like growth factors (IGF) and their binding proteins (IGFBP) play a major role in the autocrine and paracrine regulation of folliculogenesis. This is the first study that has compared follicular fluid (FF) IGF-I, IGF-II, IGFBP-3, IGFBP-4 and pregnancy-associated plasma protein (PAPP)-A concentrations, and their ratios, to investigate whether there was any difference in the intrafollicular microenvironment between the GnRH agonist (GnRHa) and antagonist (GnRHant) protocols for controlled ovarian stimulation (COS). METHODS: A total of 68 IVF cycles were included in this study; two groups were studied: GnRHa long protocol group (n = 36) and the flexible GnRHant multiple-dose protocol group (n = 32). FF was obtained from dominant follicles during oocyte retrieval and stored at -70 degrees C until assayed. IGF-I, IGF-II and IGFBP-3 concentrations were measured by radioimmunoassay and IGFBP-4 and PAPP-A by enzyme-linked immunosorbent assay. RESULTS: The duration of COS was significantly longer, and total dose of gonadotrophins used, serum estradiol (E(2)) levels on hCG day and the number of oocytes retrieved were significantly higher in the GnRHa long protocol group. The concentrations of FF IGF-II and IGFBP-4 were significantly higher, and the ratio of IGF-I/IGFBP-4 was significantly lower in the GnRHa long protocol group. Serum E(2) levels per mature follicle were not different between the two groups. CONCLUSIONS: Our data may indicate a difference of intrafollicular microenvironment between cycles using GnRHa long protocols and those using GnRHant protocols. However, the difference in microenvironment does not appear to result in a difference in clinical outcome.     

Beneficial effects of pravastatin in peri- and postmenopausal hyperlipidemic women: a 5-year study on serum lipid and sex hormone levels

Objectives: The aims of the present study are to assess the 5 year effects of pravastatin on serum lipids and lipoproteins in women around the menopause and to assess the effects of pravastatin on serum gonadotropins and sex steroid levels over a long-term period. Methods: We evaluated the long-term efficacy of pravastatin on serum lipid levels (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride) in 121 patients (47 premenopausal and 74 postmenopausal women) suffering from primary hypercholesterolemia. The effects of this lipid-lowering drug on serum gonadotropins and sex steroids (estradiol, estrone, and testosterone) are also reported. Results: Pravastatin produced a remarkable reduction in the serum total cholesterol level of 19.2±9.3% (P<0.0001) and 18.9±11.8% (P<0.0001), and in LDLl-cholesterol of 25.1±18.7% (P<0.0001) and 24±18.0% (P<0.0001) after 24 and 60 months’ treatment, respectively. In hypertriglyceridemia, pravastatin also produced a remarkable reduction in triglyceride of 29.3±27.3% (P<0.0001) and 39.9±20.4% (P<0.0001) after 24 and 60 months of treatment, respectively. We found that serum gonadotropins and sex steroid levels changed naturally as a function of age from pre-therapy levels in the premenopausal patients after 60 months of treatment. Conclusions: Pravastatin was well tolerated over 5 years and was a very effective lipid-lowering agent for both hypercholesterolemia and hypertriglyceridemia with no effect on the biosynthesis of sex steroids. These findings suggest that pravastatin can be used in the treatment of hypercholesterolemia with/without high triglyceride levels in women around the menopause.     

Secretion of insulin-like growth factor (IGF)-I and -II and IGF binding proteins (IGFBPs) in fetal stromal-vascular (S-V) cell cultures obtained before and after the onset of adipogenesis in vivo

The present study examined the influence of dexamethasone (DEX) treatment on preadipocyte differentiation and insulin-like growth factor binding protein (IGFBP) secretion in stromal-vascular (S-V) cell cultures established from subcutaneous adipose tissue obtained from nine 75 day and four 50 day pig fetuses. Cultures of S-V cells from four young pigs (5-7 days old) were also studied. Each fetal S-V cell culture represented 1 pool of S-V cells/dam. Cultures were seeded and plated in 10% FBS from day 0-3 and treated with insulin (ITS) + 10 nM DEX from day 3-6 (late DEX treatment). Alternatively, cultures were seeded and plated in 10% FBS + 80 nM DEX from day 0-3 and treated with insulin alone from day 3-6 (early DEX treatment). Conditioned media was collected on day 6 of culture after 3 days of conditioning, and prepared for subsequent 125I-IGF-I ligand blot analysis for IGFBPs and RIA for IGF-I and IGF-II. Early and late DEX increased (P<0.05) preadipocyte (AD-3+) recruitment but only early DEX increased preadipocyte differentiation (lipid + and C/EBP alpha+) by day 6 in S-V cultures from 75 day fetuses. Levels of IGFBP-2, IGFBP-4, IGF-I and IGF-II in media conditioned by 75 day fetal S-V cultures were not influenced by late DEX. However, late DEX reduced levels of 29 kDa IGFBPs and markedly increased (P<0.05) IGFBP-3 levels in 75 day S-V media. Late DEX also markedly increased (P<0.05) IGFBP-3 levels in 50 day S-V media but had little influence on other IGFBPs. Early DEX treatment increased (P<0.05) IGFBP-4 levels in 75 day S-V media but had little to no influence on levels of IGF-I, IGF-II and other IGFBPs. These studies indicate that IGFBP-4 may regulate local metabolism during preadipocyte differentiation, whereas IGFBP-3 may antagonize preadipocyte differentiation by targeting IGF-I away from differentiating cells and towards growing cells.     

Drug concentration effect relationship of estradiol from two matrix transdermal delivery systems: Menorest and Climara

Objectives: To relate the pharmacokinetics of estradiol to pharmacological effects. Methods: Drug concentration effect relationship of estradiol from two matrix transdermal delivery systems, Menorest® and Climara®, was studied in a single centre, open, randomised, comparative crossover study. The trial consisted of two treatment periods, 14 days for each patch separated by a 4-week washout period. Blood hormone levels were followed during the second week of each treatment. Estradiol levels during treatments were related to three concentration levels previously proposed as efficacy or safety limits. The effect of treatment on FSH-levels was examined and the relationship between the levels of estradiol and FSH was described using an inhibitory sigmoidal I_max model. Estrone levels and estradiol/estrone before and during treatment were followed. Results: The C_average of FSH during treatment was 38% lower than baseline plasma levels. Estradiol had an inhibitory effect on FSH with an I_max of 0.68 and an IC₅₀ of 19 pg/ml. The fraction of time above the minimum concentration for therapeutic effect and the tolerability limit did not differ between the two treatments, whereas the fraction of time above the suggested threshold for osteoporosis prophylaxis was significantly larger for Menorest® than for Climara® (P<0.05). The low baseline estradiol/estrone ratios increased towards pre-menopausal levels during treatment. Conclusions: The drug concentration effect relationship of estradiol may be of use in evaluation of the effects of prophylactic estrogen therapy and to facilitate comparisons between different forms of estrogen treatments.     

The values of urinary NTx in postmenopausal women undergoing HRT; the role of additional alendronate therapy

Objective: To determine the changes in levels of urinary NTx at the end of the 6th month of oral and transdermal hormone replacement therapy (HRT) and the effects of additional alendronate therapy for osteoporotic women. Method: Of 66 postmenopausal women 23 were treated with oral estradiol+norethisterone acetate (E+P), and 22 were treated with transdermal estradiol+norethisterone acetate. The third group consisted of 21 women with osteoporosis (bone mineral density<100 mg/cm³) and treated with oral E+P plus alendronate 10 mg/day. Result: Significant decreases of urinary NTx levels were seen after HRT in all study groups (P<0.05). But the decline of NTx levels was not different between the oral and transdermal HRT groups (P>0.05). There was no additional decrease in the levels of NTx with alendronate therapy (P>0.05) but NTx excretion diminished more in patients with high baseline levels. Conclusion: The decline of NTx at the end of the 6th month of HRT reflects the decrease of bone resorption and it is not related to the route of administration.     

Radio-immunoassay of salivary progesterone for monitoring ovarian function in female infertility

Fifty-two women, aged from 25 to 41 years, with infertility due to chronic anovulation were admitted to the study together with 36 age-matched controls with proven ovulatory cycles. Paired plasma (3 ml) and whole unstimulated saliva (10 ml) samples were collected over a 30 day period, starting from the first day of a menstrual bleeding, in patients, and throughout the menstrual cycle, in controls. Salivary progesterone levels, measured in women with infertility, ranged from undetectable values to 16 pmol/l during the first, and from 36 to 98 pmol/l during the second half of the monitoring period. In eugonadal women the steroid levels ranged from 34 to 46 pmol/l and from 96 to 780 pmol/l during the follicular and luteal phases, respectively. The saliva/plasma progesterone ratio ranged from 0.58 to 2.71 p. cent and a good correlation between salivary and plasma levels was found at each time of monitoring. Many (86 p. cent) of patients, which were randomly allocated to a low- or high-dose epimestrol administration schedule, appeared to be sensitive to the drug, achieving, after therapy, salivary progesterone levels which were within the range of controls. Since correct assessment of luteal function in basal conditions and during therapy requires multiple steroid measurements, and since saliva can be obtained by non-invasive techniques, salivary assays represent an attractive alternative to plasma ones for monitoring ovarian activity, also during specific treatment.     

Ovarian testosterone secretion during perimenopause

Objective: The aim of the study was to investigate ovarian testosterone secretion during the last few years of reproductive life and after menopause. Materials and methods: Ovarian and peripheral venous levels of total testosterone were analyzed in 52 women aged 42–69 years (mean 51) undergoing hysterectomy with adnexal removal for benign indications at the Department of Obstetrics and Gynecology at Tampere University Hospital, Finland. The study population was divided into pre- (n=19), peri- (n=18) and postmenopausal (n=15) women in addition to the classical division according to menstrual cycle. Corresponding serum estradiol, progesterone and gonadotropin levels were measured, and the degree of ovarian stromal hyperplasia was analyzed. Results: The levels of all steroid hormones were higher in the ovarian vein than in the periphery. A significant positive correlation was found between age and ovarian vein testosterone levels (r=0.3, P=0.01). In premenopausal women, it was 1.5 nmol/l (median; range 0.78–6.0), in perimenopausal women 2.2 nmol/l (range 0.9–13.6), and 2.5 nmol/l (range 0.6–26.6) in postmenopause, respectively. Peripheral testosterone level did not increase with age. Ovarian stromal hyperplasia was significantly associated with increased testosterone secretion (P=0.009). Conclusion: The ovary seems to increase the secretion of testosterone into circulation during the menopausal transition period, as the highest levels were measured in postmenopausal women. High testosterone levels in the ovarian vein, however, were not reflected in the peripheral venous blood.