Medroxyprogesterone abrogates the inhibitory effects of estradiol on vascular smooth muscle cells by preventing estradiol metabolism

Sequential conversion of estradiol (E) to 2/4-hydroxyestradiols and 2-/4-methoxyestradiols (MEs) by CYP450s and catechol-O-methyltransferase, respectively, contributes to the inhibitory effects of E on smooth muscle cells (SMCs) via estrogen receptor-independent mechanisms. Because medroxyprogesterone (MPA) is a substrate for CYP450s, we hypothesized that MPA may abrogate the inhibitory effects of E by competing for CYP450s and inhibiting the formation of 2/4-hydroxyestradiols and MEs. To test this hypothesis, we investigated the effects of E on SMC number, DNA and collagen synthesis, and migration in the presence and absence of MPA. The inhibitory effects of E on cell number, DNA synthesis, collagen synthesis, and SMC migration were significantly abrogated by MPA. For example, E (0.1micromol/L) reduced cell number to 51+/-3.6% of control, and this inhibitory effect was attenuated to 87.5+/-2.9% by MPA (10 nmol/L). Treatment with MPA alone did not alter any SMC parameters, and the abrogatory effects of MPA were not blocked by RU486 (progesterone-receptor antagonist), nor did treatment of SMCs with MPA influence the expression of estrogen receptor-alpha or estrogen receptor-beta. In SMCs and microsomal preparations, MPA inhibited the sequential conversion of E to 2-2/4-hydroxyestradiol and 2-ME. Moreover, as compared with microsomes treated with E alone, 2-ME formation was inhibited when SMCs were incubated with microsomal extracts incubated with E plus MPA. Our findings suggest that the inhibitory actions of MPA on the metabolism of E to 2/4-hydroxyestradiols and MEs may negate the cardiovascular protective actions of estradiol in postmenopausal women receiving estradiol therapy combined with administration of MPA

Effects of the progestagen-only contraceptive implant Implanon on transforming growth factor beta1 and endothelin-1

Progestagen-only contraceptives are often prescribed to women with an increased cardiovascular risk, despite the fact that only few data are available on the effect of these contraceptives on circulating biomarkers of inflammation and endothelial function. In our prospective case-control study, we aimed to investigate the influence of the low-dose etonogestrel-releasing contraceptive implant Implanon® on endothelin-1 and cytokine transforming growth factor β (TGF-β1), both factors involved in the early phases of atherogenesis. We also were interested in searching for an interrelation between changes in these two parameters and changes in female hormones and plasma lipids. Cases (n=20) were women using Implanon® for contraception, and controls (n=20) were females not using hormonal contraception. Baseline blood samples were taken during the early follicular phase of cycle 1 in both groups. A second sample was taken 12 weeks after Implanon® insertion or, for controls, in the early follicular phase of cycle 4. In both groups no significant change in endothelin-1 or TGF-β1 was observed. In Implanon® users, cholesterol, high-density lipoprotein, low-density lipoprotein, sex hormone-binding globulin, and testosterone decreased significantly. No correlations were found between endothelin-1 or TGF-β1 and the investigated parameters. The results suggest that Implanon® does not exert a clinically relevant negative effect on endothelin-1 or TGF-β

Effects of the progestagen-only contraceptive implant Implanon® on cardiovascular risk factors

Objective: Epidemiological studies on the cardiovascular risk of progestagen-only contraceptives are rare. With the present study we aimed to investigate the effect of the low-dose etonogestrel-releasing contraceptive implant Implanon® on cardiovascular risk factors, including markers of inflammation. Design: Longitudinal study. Setting: Family planning centre of a University Hospital. Subjects: Thirty-six healthy, nonsmoking women with regular cycles (n = 18 controls without hormonal contraception; n = 18 cases requesting the insertion of Implanon®). Measurements: Blood samples for the determination of C-reactive protein (CRP), nitric oxide (NO), sex hormones and plasma lipids were taken in the early follicular phase of the cycle in both groups. A second sample was taken 12 weeks after Implanon insertion or in the controls during the early follicular phase of cycle 4. Results: Implanon treatment caused a 36% decrease in CRP (P < 0·06) and a significant decrease in high density lipoprotein (HDL) (P < 0·007), low density lipoprotein (LDL) (P < 0·001), cholesterol (P < 0·001), testosterone (P < 0·05) and SHBG (P < 0·002). Levels of NO, oestradiol and progesterone were not affected in either group. The cholesterol/HDL ratio did not change in Implanon carriers. There was a significant correlation between the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. Conclusion: The progestagen-only implant Implanon does not exert a negative effect on the cardiovascular risk factors CRP, cholesterol/HDL ratio and NO. These results suggest that the use of a progestagen-only contraception does not increase cardiovascular risk factors in healthy young women

Gewichtsveränderung unter hormonalen Kontrazeptiva: Mythos oder Wahrheit?

Viele Frauen befürchten einen Gewichtsanstieg bei der Anwendung von Hormonen zur Verhütung. Angst vor Gewichtszunahme kann besonders junge Frauen von einer sicheren Verhütung abhalten oder zum vorzeitigen Absetzen führen. Im folgenden Artikel geben wir eine Übersicht von Studien, welche die Gewichtsveränderung unter verschiedenen Verhütungsmethoden dokumentieren. Bei der Mehrheit der Frauen bleibt unter hormonalen Kontrazeptiva über die kurze Studiendauer (6-24 Monate) das Körpergewicht stabil (±3 kg). Unter Depo Provera® erfolgt jedoch bei einigen Frauen eine starke Gewichtszunahme: Der Teil an stark zunehmenden Frauen (>3 kg/Jahr) ist grösser als bei anderen hormonellen Methoden. Auch die Studien mit Trägerinnen eines Intrauterinpessars zeigen eine Gewichtszunahme, welche etwa das Doppelte der Zunahme der durchschnittlichen weiblichen Bevölkerung beträgt. Alle Frauen nehmen mit den Jahren an Gewicht zu (0,1 kg/m2 pro Jahr, entspricht etwa 0,3 kg/Jahr). = Weight gain is one of the side effects often attributed to the use of hormonal contraception. Concern about weight gain can hinder particularly young women to use a safe contraceptive method or may be a reason for early discontinuation. In the following review, we present studies examining the influence of different contraceptive methods on weight change and discuss the results and methodological problems. During use of hormonal contraceptives, weight fluctuates by about 3 kg over an observation interval from 6 to 24 months. Only in a subgroup of Depo Provera users is the increase in weight higher: the proportion of women gaining >3 kg/year is higher compared with the other hormonal contraceptives. Interestingly users of intrauterine devices experience a weight gain too, which is approximately double that of the average female population. The age-associated weight gain has been described to be 0.1 kg/m(2) annually, corresponding to about 300 g/year

Implanon use lowers plasma concentrations of high-molecular-weight adiponectin

OBJECTIVE: To investigate the effect of the low-dosed etonogestrel-releasing contraceptive implant Implanon on new cardiovascular risk markers, we studied the effect of this implant on adiponectin and its metabolically important isomer high-molecular-weight adiponectin (HMW). Low-dosed progestagen-only contraception is preferentially prescribed to females with increased cardiovascular risks. DESIGN: Longitudinal study. SETTING: Family-planning center of a university hospital. PATIENT(S): Forty healthy nonsmoking women with regular cycles (n=20 controls without hormonal contraception; n=20 cases wishing the insertion of Implanon). INTERVENTION(S): Blood samples for the measurements of adiponectin, HMW, C-reactive protein (CRP), sex hormone binding globulin, sexual hormones, and plasma lipids were taken in the early follicular phase of the cycle in both groups. A second sample was taken 12 weeks after Implanon insertion or in the controls during the early follicular phase of cycle four. MAIN OUTCOME MEASURE(S): At baseline there was a significant correlation between adiponectin and the parameters hsCRP and high-density lipoprotein. Implanon treatment caused a significant decrease in HMW and the HMW/adiponectin ratio. Additionally plasma lipids (cholesterol, high-density lipoprotein, low-density lipoprotein), sex hormone binding globulin, and testosterone levels decreased significantly. Adiponectin plasma concentrations were not affected. CONCLUSION(S): Short-term Implanon use in healthy premenopausal women was associated with a decrease in the cardioprotective adiponectin isomer HMW. It remains to be investigated if this decrease persists after longer use of the implant

No effect of Implanon® on inflammatory cardiovascular parameters

Objective. Recently, we found decreased levels of C-reactive protein (CRP) during use of the low-dosed contraceptive implant Implanon1. To further elucidate, whether this finding might be a sign for a lower inflammatory reaction and is associated with changes in levels of other cytokines, we investigated the effect of this implant on interleukin-6 (IL-6) and adiponectin. Plasma lipids and sex hormone levels have been shown to interact with the investigated parameters in vivo and in vitro. Therefore these parameters were measured as well. Design. Prospective case–control study. Setting. Family-planning centre, University hospital. Subjects. Thirty-six non-smoking women with regular cycles. Interventions. Blood samples for the measurements were taken in the early follicular phase of the cycle in both groups. A second sample was taken 12 weeks after Implanon insertion or in the controls during the early follicular phase of cycle 4. Results. Implanon did not cause significant changes in IL-6, adiponectin or lipoprotein (Lp)(a). At baseline, there was a significant positive correlation between IL-6 and CRP and a negative correlation between adiponectin and CRP. Conclusion. We did not observe a negative impact of Implanon on risk markers for atherosclerotic disease such as IL-6, adiponectin, and Lp(a). These data are reassuring for clinicians who prescribe progestagen-only preparations as first choice contraceptives in females with cardiovascular risk factors. Keywords: Contraception, cardiovascular risk, inflammatory markers, Implanon1, hormonal contraception, progestagen

Estradiol induces mitogenesis in human progenitor endothelial cells (PECs) by upregulating cyclins and downregulating p21

Circulating progenitor endothelial cells (PECs) play a critical role in repairing damaged endothelial layer. Since estradiol is vasoprotective (1), it may promote vascular endothelial recovery by inducing PEC-proliferation. Here we investigated the growth effects of estradiol on human PECs and the intracellular mechanisms involved

Serum concentrations of high-molecular weight adiponectin and their association with sex steroids in premenopausal women

At present, the association between adiponectin and sex hormones in women is controversial. Recent studies suggest that it is high-molecular weight (HMW) adiponectin and the HMW to total adiponectin ratio rather than total adiponectin that are associated with antiatherogenic activities, insulin sensitivity, metabolic syndrome, and prediction of cardiovascular events. The present study aimed to investigate whether measuring HMW adiponectin and the HMW to total adiponectin ratio rather than total adiponectin might be more useful to detect an association between circulating female sex steroids and adipocytokines. In a clinical trial, we investigated the associations of total adiponectin, HMW adiponectin, and the HMW to adiponectin ratio with several androgens and estradiol in 36 healthy premenopausal women with regular cycles. No association between the investigated sex hormones and adiponectin was observed. The HMW adiponectin was negatively correlated with estradiol after adjustment for age and body mass index. The HMW to total adiponectin ratio was significantly negatively associated with testosterone, free testosterone, and androstenedione. The testosterone to estradiol ratio, as a parameter for the estrogen-androgen balance, was not associated with adiponectin or the HMW isoform. In conclusion, there is a negative association between estradiol and HMW adiponectin, and between testosterone, free testosterone, and androstenedione and the HMW to adiponectin ratio. Thus, one mechanism whereby female sex steroids may influence the cardiovascular risk of women could be alteration of the relationship between HMW and total adiponectin concentrations in plasma

Comparison of quartz vials with polypropylene vials for rapid cryopreservation of human ovarian tissue

BACKGROUND: Because higher survival of follicles during the freezing/thawing procedure improves the quality of cryopreserved tissue reimplanted after oncological therapies, defining an optimal method for human ovarian tissue cryopreservation remains a major issue in this field. One option to improve the cryopreservation procedure is to use better materials, i.e., vials with better conductivity. The aim of this study was to compare polypropylene (PP) with quartz vials. Between September 2012 and January 2013, eight patients were recruited. The ovarian cortex was cut into 3 slices, assigned randomly to a fresh and a cryopreserved group in PP (method B) or quartz vials (method C). Histological and immunohistochemical (IHC) analysis were used. For IHC three antibodies were analyzed: Ki67 (proliferation index), Bcl2 (anti apoptotic index) and Hsp70 (stress index). RESULTS: The majority of GCs showed positive staining for Bcl2 in both cryopreservation device, with higher expression in group C than in group B. Oocytes and their nuclei showed intense positive staining for ki67 in both methods B and C, and also a patch positive stromal cells staining for Ki67. Expression of hsp70 was not increased after cryopreservation. CONCLUSIONS: Cryopreservation using quartz vials led to larger numbers of good follicles while maintaining consistent preservation for stromal cells and vessels