Serum pattern of circulating free leptin, bound leptin, and soluble leptin receptor in the physiological menstrual cycle

OBJECTIVE: To investigate the serum pattern of free leptin, bound leptin, and soluble leptin receptor throughout the physiological menstrual cycle. DESIGN: Prospective observational study. SETTING: Tertiary care center for gynecological endocrinology and reproductive medicine and a university research laboratory. PATIENT(S): Thirty regularly cycling volunteers (age, 29 +/- 4.2 years). INTERVENTION(S): Blood sampling was performed at different phases (early and mid follicular phase, preovulatory phase, and early and late luteal phase) of three consecutive menstrual cycles; each phase of the menstrual cycle was investigated twice. MAIN OUTCOME MEASURE(S): Free leptin, bound leptin, soluble leptin receptor, LH, E(2), P, vaginal ultrasound. RESULT(S): A peak of serum free leptin levels was found in the late luteal phase followed by a significant drop in the early follicular phase and again by a continuous increase up to the next luteal peak. There were no significant alterations in serum bound leptin and soluble leptin receptor levels. CONCLUSION(S): The present study shows that there are significant circacyclic fluctuations of free leptin levels with the highest concentrations in the late luteal phase and the lowest levels in the early follicular phase, which suggests that circulating free leptin is up-regulated by the C(21)-steroid (P). Circulating bound leptin and soluble leptin receptor are not altered by the cyclic hormone status. The significant rise of the leptin bioequivalent, free leptin, in the late luteal phase might be of importance for the luteal-follicular and the luteal-preimplantatory functional shift.     

Food intake and leptin concentrations of lactating rats nursing various sized litters

Purpose:   Leptin, the obesity ( ob ) gene product, has been proposed as an adipose-related satiety factor. It might act as a signal, from peripheral adipose stores to the central nervous system, to decrease food intake and increase energy expenditure. Conversely, low leptin concentrations after fasting or energy restriction might act to increase food intake. The present study investigated the role of the suckling stimulus in the mechanisms regulating body weight, food consumption and leptin concentration in lactating rats nursing different sized litters.
Methods:   The day of parturition was designated as day 0 of lactation. The rats were allocated randomly to three groups and the number of pups per litter was adjusted within one day of birth to eight (Group A), four (Group B) and two (Group C), with equal numbers of both sexes. From day 1 to day 10 of lactation, the separate weights of the mothers and pups, and the mothers' food intake were measured daily. On day 10, the rats were decapitated and blood was collected from the mothers for measurement of serum concentrations of leptin by ELISA.
Results:   Food intake by the mothers in Groups B and C decreased by about 20% and 30%, respectively, by day 10 of lactation, compared with Group A, but the serum leptin concentrations of those in Group C increased by about 80%, compared with Groups A and B. There was a high positive correlation between leptin concentration and fat pad weight.
Conclusion:   The findings suggest that the smaller litter in Group C reduced the energy cost of lactation, which induced an increase in the serum leptin concentration. (Reprod Med Biol 2005; 4 : 203–206)     

The effects of soygerm extracts on blood lipoproteins, antioxidative capacity and urinary estrogen metabolites in postmenopausal women on hormone therapy.

OBJECTIVE: To evaluate the effects of soygerm isoflavones extracts on blood lipoproteins, antioxidative capacity and urinary estrogen metabolites in postmenopausal women who receive hormone therapy (HT). METHOD: Thirty-nine volunteers receiving HT were recruited, and 33 completed the study. All subjects received 6 g of soygerm extracts per day for 4 weeks. Blood and urine samples were collected for study at the beginning and at the end of study. RESULT: Plasma HDL-C levels increased markedly with significant decreases of plasma LDL-C/HDL-C ratio and LDL-TG levels. The lag time of conjugated dienes formation prolonged for 9.9% and thiobarbituric acid reactive substances production in copper-catalyzed oxidation of LDL decreased. The differences were statistically significant. Urinary ratio of 2-OHE(1) to 16alpha-OHE(1) increased without statistical significance. CONCLUSION: Soygerm extracts may improve serum lipid profile in postmenopausal Taiwanese women who receive HT, and probably provide a favorable effect on estrogen metabolism.     

Comparison of static and dynamic balance during early follicular and ovulation phases in healthy women,using simple,clinical tests: a cross sectional study

Balance may be influenced by several factors. The menstrual cycle can be considered as an important factor which may affect postural control. This study was aimed to investigate the influence of early follicular and ovulation phases on static and dynamic balance indices. Thirty non-athlete healthy women with a regular menstrual cycle aged between 18 and 25 years participated in the study. Static balance was evaluated through single-leg stance test and dynamic balance was investigated with posteromedial direction of Y- balance test during early follicular and ovulation (24–48?hours after the peak of estrogen) phases of menstrual cycle. The balance tests were performed in a randomized order in each session. A paired t-test analysis was performed to compare the data during the early follicular and ovulation phases. The results indicated that both static and dynamic balance scores were higher in ovulation phase in comparison to early follicular phase (p?<?.001). It is worth noting to consider the balance fluctuations during different phases of menstrual cycle when prescribing exercise programs for healthy women or when they participate in sport or recreational activities.     

Serum leptin concentrations in pre- and postmenopausal women on sex hormone therapy.

AIM: The aim of the present study was to investigate the influence of endogenous estradiol and estrogen and estrogen-progestin therapies on concentration in pre- and postmenopausal women. MATERIALS AND METHODS: The study groups consisted of 26 women with surgical menopause (mean+/-standard deviation (SD): age 51.8+/-2.6 years, body mass index (BMI) 26.45+/-4.56 kg/m(2)), 54 with natural menopause (mean+/-SD: age 50.5+/-3.0 years, BMI 25.75+/-4.09 kg/m(2)) and 40 premenopausal controls (mean+/-SD: age 48.3+/-2.3 years, BMI 26.23+/-4.12 kg/m(2)). The group with surgical menopause received estradiol transdermally (50 microg/day) and those with natural menopause received additionally medroxyprogesterone acetate (5 mg/day) for the last 12 days of the cycle. Before and after 4 months of therapy, body weight, waist and hip circumferences and blood pressure were measured, and BMI and waist-to-hip ratio (WHR) were calculated. Serum leptin, follicle-stimulating hormone (FSH), estradiol (E(2)), testosterone, prolactin and dehydroepiandrosterone sulfate (DHEAS) were measured prior to and after treatment. RESULTS: Leptin concentrations did not differ statistically among the groups. No correlations between leptin and E(2), FSH, prolactin, testosterone and DHEAS concentrations were found in any of the groups before and after treatment. Leptin level correlated positively with body mass, BMI and hip and waist circumferences in all groups. There were no correlations between leptin and WHR in the pre- and postmenopausal groups. In the premenopausal group and in some postmenopausal groups, serum leptin level correlated with blood pressure. CONCLUSIONS: Endogenous E(2) and androgens in premenopausal women and estrogen and estrogen-progestin therapies in postmenopausal subjects do not influence serum leptin concentrations. Leptin level is related to body mass and BMI, but not to sex hormone status. The distribution of adipose tissue and the type of obesity (android or gynoid) have no influence on serum leptin concentration. The correlation between serum leptin level and blood pressure requires further investigation.     

The effect of estradiol on urodilatin production in postmenopausal women

Urodilatin, which is structurally homologous to atrial natriuretic peptide, is most probably synthesized in the kidney. It inhibits water and sodium reabsorption and causes renal vasodilatation. However, little is known about the regulation of its synthesis, especially with regard to the influence of hormones. Transdermal administration of estradiol with low dosage producing physiologic conditions, and oral administration of estradiol with high pharmacologic dosage were investigated for their effect on urodilatin production in postmenopausal women measuring urinary excretion. Both routes of administration of estradiol increased urodilatin excretion after 28 days of treatment, the increment being statistically significant only for the transdermal route. The increased urodilatin production registered after transdermal estradiol replacement therapy may suggest that estradiol has a vasodilatory effect on the kidney. Accepted: 14 March 1998     

Optimizing soy isoflavones effect in postmenopausal women: the impact of timing on climacteric symptoms

Background.?The most common complaints during climacteric are vasomotor symptoms. A circadian rhythm has been observed when hot flashes start; however, not much information is available in this field.

Aims.?To analyze whether the time (morning/evening) of administration of a compound containing 60 mg of dry soy seed extract (glycine max) with 40% of total isoflavones, primrose oil and α-tocopherol modifies the effect on the climacteric syndrome.

Trial design.?Multicentric, observational, open, prospective, longitudinal and cross-sectional study.

Subjects and methods. One thousand six hundred eighty-two postmenopausal women with climacteric symptoms were allocated in two groups in order to receive the treatment in the morning (Group 1) or in the evening (Group 2), switching administration time after 3 months. Clinical evaluation was carried out at 0, 3 and 6 months of follow-up using Blatt–Kupperman and Greene scales

Results.?233 (13.9%) women dropped out from the study. Both administration times improved the climacteric symptoms after 3 and 6 months of treatment, showing a reduction in the scores of Blatt–Kupperman and Greene scales (p?<?0.001). No differences between both groups during the follow-up were identified.

Conclusions.?The time of administration of isoflavones does not modify its effect on climacteric symptoms.     

Changes in copper and zinc plasma concentrations during the normal menstrual cycle in women

Objective.?To investigate whether there is a fluctuation of the copper and zinc plasma levels during the menstrual cycle and if this correlates to the physiological fluctuations of estradiol and progesterone plasma concentrations in eumenorrhoic women.

Methods.?We studied 14 eumenorrhoic women. Copper (Cu), zinc (Zn), estradiol (E2) and progesterone (Prg) plasma concentrations, during time of menstruation (time 1), midfollicular phase (time 2), time of ovulation (time 3) and midluteal phase (time 4) were determined.

Results.?We observed significant changes in both copper plasma concentrations and zinc plasma concentrations during the four times studied (p?<?0.05). The changes of Cu during the various phases correlated negatively with the changes in E2 (r?>?0.5, p?<?0.05), whereas the changes of Zn correlated positively with those of E2 (r?>?0.8, p?<?0.05). We were unable to demonstrate any statistically significant correlation between Cu and Prg or Zn and Prg.

Conclusions.?This study indicates that there is a cyclic fluctuation of Cu and Zn concentrations in plasma during the menstrual cycle, in healthy eumenorrhoic women. This cyclic fluctuation might be due to the cyclic fluctuation of plasma levels of E2.     

Hysteroscopic polypectomy in 240 premenopausal and postmenopausal women

OBJECTIVE: To ascertain the therapeutic efficacy and safety of hysteroscopic polypectomy in 240 premenopausal and postmenopausal patients. DESIGN: Retrospective study. SETTING: Tertiary university hospital. PATIENT(S): Two hundred forty patients with intrauterine endometrial polyps, who mostly suffered from abnormal uterine bleeding and infertility. INTERVENTION(S): Hysteroscopic polypectomy using various instruments including microscissors, grasping forceps, or electrosurgery either with a monopolar probe or a resectoscope. MAIN OUTCOME MEASURE(S): Operating time, amount of glycine absorption, complications, resumption of normal menstruation, cumulative pregnancy rate, and recurrent rate of polyps after hysteroscopic surgery. RESULT(S): Resectoscopic polypectomy needed more operating time, had more glycine absorption and complications, but less recurrence than other hysteroscopic techniques. The resectoscope had a 0% recurrence rate and that grasping forceps had a 15% recurrence rate. A total of 21 (8.7%) complications occurred, but no major complications were noted. After long-term follow-up of 9 years and 2 months, those with abnormal uterine bleeding resumed normal menstruation in 93.1% and those with infertility had a cumulative pregnancy rate of 42.3%. There was no statistical difference in reproductive outcome between patients having polyps < or = 2.5 cm and >2.5 cm. CONCLUSION(S): We found hysteroscopic polypectomy to be effective, safe, minimally invasive procedure with low rate and mild complications. Restoration of reproductive ability did not depend on the size of the removed lesion. Resectoscopic surgery is more preferable to prevent recurrence of polyps.     

Lack of effect of isoflavonoids on the vagina and endometrium in postmenopausal women

OBJECTIVE: To determine the effects of soy-derived isoflavones on vaginal epithelium and the endometrium. DESIGN: Double-blind, randomized, placebo-controlled crossover trial. SETTING: Outpatient clinic of a university hospital. PATIENT(S): Sixty-four postmenopausal women with a history of breast cancer. INTERVENTION(S): The women took (in a randomized order) 114 mg of isolated isoflavonoids or placebo in tablets daily for 3 months; the treatment regimens were crossed over after a 2-month washout period. The subjects were studied before and on the last day of each treatment period. MAIN OUTCOME MEASURE(S): Vaginal dryness, maturation index (MI) of vaginal epithelium, endometrial thickness, histology, and expression of estrogen (E) and progesterone (P) receptors and the proliferation marker Ki-67 in the endometrium. RESULT(S): Isolated isoflavones did not relieve vaginal dryness. Maturation index values remained unchanged during the isoflavone regimen, but decreased during the placebo regimen. No changes were found in any of the variables measured in the endometrium. CONCLUSION(S): Daily administration of 114 mg of isolated isoflavones for 3 months had no effect on the subjective perception of vaginal dryness or on objective findings in the vagina or endometrium. This implies safety with regard to the endometrium.     

The effects of phytoestrogen therapy on the endometrium in postmenopausal women

AIM: The purpose of the present study was to carry out a comparative histological analysis of the endometrium in postmenopausal women who made use of phytoestrogens in order to assess the efficacy and possible side effects of this therapy. METHODS: This study was carried out by forming 2 groups in order to compare the results. One group was given a dietary supplement of phytoestrogens for 24 months, whereas the other was given a placebo for the same period of time. At the beginning of this study endometrial bioptical samples were taken from those patients who had been previously selected at our University Centre. This study was started only with those postmenopausal patients whose bioptical sample was histologically suitable, and it was neither hyperplastic, nor cancerous and nor secretive. During these 24 months there have been frequent contacts aimed at verifying the standard therapeutic behaviour, symptoms and appearance of side effects. At the end of the study new and final bioptical samples of endometrium were taken from both groups. RESULTS: One-hundred and forty-one patients completed the study. Five patients (3.4%) who were submitted to phytoestrogens therapy showed a weak proliferative endometrium bioptical sample. All the other biopsies at the beginning and at the end of the study showed an atrophic and inactive sample. Hot flushes, night sweats, vaginal dryness and dyspareunia improved at the end of the study for the group treated with phytoestrogens as compared to the one treated with a placebo. Although there have not been very significant differences ias to symptoms and side effects, it was noted that insomnia was the most common symptom in the group treated with non-hormonal therapy based on phytoestrogens. CONCLUSIONS: Phytoestrogens did not cause any sensitive and worrisome stimulation of the endometrial mucosa. Insomnia was more frequent in the group treated pharmacologically in the 24 months of the study, whereas hot flushes, night sweats, vaginal dryness and dyspareunia persisted or increased as compared to the beginning of the study in the group treated with a placebo, but this did not occur for the group treated with phytoestrogens.     

Leptin and leptin receptor levels in pregnant women with hyperemesis gravidarum

OBJECTIVE: To investigate the association between the leptin, leptin receptor and hormone levels and hyperemesis gravidarum, and to determine whether these two parameters may be early markers for hyperemesis gravidarum. METHODS: The study group consisted of 18 pregnant women with hyperemesis gravidarum and the control group consisted of 18 healthy pregnant women. Demographic characteristics were recorded and body mass index (BMI) values were calculated for all the pregnant women. Serum leptin, leptin receptor, insulin, cortisol, thyroid hormone and human chorionic gonadotrophin (hCG) levels were measured. RESULTS: When the two groups were compared with respect to leptin levels, the group with hyperemesis gravidarum was found to have significantly higher leptin levels (P = 0.037). No intergroup differences were observed in serum cortisol, insulin, hCG, thyroid hormone levels or BMI values. In the group with hyperemesis gravidarum, an inverse correlation was detected between cortisol and leptin (r = -0.762, P < 0.01), and hCG and thyroid-stimulating hormone (r = -0.503, P < 0.05), whereas a significant correlation was detected between insulin and leptin (r = 0.538, P < 0.05), leptin and BMI (r = 0.711, P < 0.01), and between TT3 and hCG (r = 0.605, P < 0.01). CONCLUSION: It was concluded that leptin could play a role in, and be defined as, a marker of hyperemesis gravidarum.     

Relationships between circulating leptin concentrations and other hormonal parameters in obese and non-obese women with polycystic ovary syndrome

Aim: To clarify the role of leptin in women with polycystic ovary syndrome (PCOS), we analyzed whether serum leptin levels correlate with other hormonal parameters in obese and non-obese women with PCOS.
Methods: We studied 20 obese (body mass index, BM ≥25 kg/m²) and 20 non-obese (BMI <25 kg/m²) women with PCOS diagnosed by the existence of menstrual disturbance, elevated serum level of luteinizing hormone (LH) with normal follicle-stimulating hormone (FSH) and the characteristic polycystic appearance of the ovaries on transvaginal ultrasound images. Blood samples for LH, FSH, estradiol, testosterone (T), androstenedione (Δ₄) and leptin were obtained, and the relationships between variables were examined by calculating Spearman correlation coefficients.
Results: Mean levels of leptin, T and Δ₄ in obese PCOS women were significantly higher than those in non-obese PCOS women, but this was not the case for BMI, bodyweight and waist to hip ratio. In all the 40 PCOS women considered together, there were significant positive correlations of leptin with BMI, waist to hip ratio, and Δ₄ levels. However, in each group separately, serum leptin levels in obese PCOS women correlated only with BMI and bodyweight, whereas serum leptin levels in non-obese PCOS women correlated with serum A4 levels.
Conclusion: Although further study is needed to assess the role of leptin on ovarian function in non-obese women with PCOS, present findings do not support the fact that leptin is involved in the development of hormonal abnormalities in obese women with PCOS. (Reprod Med Biol 2002; 1 : 49–54)     

Role of postmenopausal hormone replacement therapy on body fat gain and leptin levels

During menopause women tend to gain body fat. The increase in adiposity seems to be a consequence of the decline in endogenous estrogens and the reduced energy expenditure. The role of post-menopausal hormone replacement therapy (pHT) in modulating visceral obesity is controversial. Some studies have shown that pHT has no effect on body weight while in other studies pHT increased body weight. Leptin is an adipocyte-derived hormone and its levels reflect the amount of adipose tissue. Obesity is associated with elevated serum leptin levels. The effect of pHT on leptin levels is also controversial. In some studies pHT increased leptin levels while other studies have not confirmed this increasing effect. The major problem encountered during administration of hormone therapy seems to be the timing of pHT initiation which is a strong confounder on the effect of pHT on leptin levels in postmenopausal women.     

Association of serum leptin with bone mineral density in postmenopausal osteoporotic females

Objective: Present study was designed to find out whether leptin is a predictor of bone mass density (BMD) in premenopausal women (PMW) and postmenopausal osteoporotic women (PMOPW) or it has no association with BMD.

Methods: One hundred and ninety two women (98 PMOPW and 94 PMW) were recruited for this study. The control group was BMI matched with osteoporotic subjects. BMD assessment was done on calcaneus by peripheral ultrasound bone densitometry and T scores were determined. Serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA).

Results: Serum leptin and BMD values were significantly different in both groups (leptin, 18.56?±?8.65?ng/ml versus 21.64?±?9.80?ng/ml, p?=?0.02) and (BMD, ?0.70?±?0.19 versus ?3.17?±?0.59, p?=?0.000), respectively. In PMOPW serum leptin and BMD were considerably correlated with weight (lep, r?=?0.53, p?=?<0.001; BMD, r?=??0.21, p?=?0.02), BMI (lep, r?=?0.52, p =?<0.001; BMD, r?=??0.27, p?=?0.005), waist circumference (lep, r?=?0.61, p?=?<0.001; BMD, r?=?0.18, p?=?0.04), hip circumference (lep, r?=?0.58, p?=?<0.001).

Multivariate linear stepwise regression analysis showed that weight and BMI in PMW and PMOPW were independent predictors of BMD. Serum leptin level was not found to be the predictor of BMD in both groups.

Conclusion: The present results indicate that body weight and BMI have an impact on BMD while serum leptin is not associated with BMD in PMW and PMOPW.