The Role of Ovarian Suppression in Premenopausal Women Is an Evolving Story

1995 ◽  
Vol 74 (05) ◽  
pp. 1271-1275 ◽  
Author(s):  
C M A Henkens ◽  
V J J Bom ◽  
W van der Schaaf ◽  
P M Pelsma ◽  
C Th Smit Sibinga ◽  
...  

SummaryWe measured total and free protein S (PS), protein C (PC) and factor X (FX) in 393 healthy blood donors to assess differences in relation to sex, hormonal state and age. All measured proteins were lower in women as compared to men, as were levels in premenopausal women as compared to postmenopausal women. Multiple regression analysis showed that both age and subgroup (men, pre- and postmenopausal women) were of significance for the levels of total and free PS and PC, the subgroup effect being caused by the differences between the premenopausal women and the other groups. This indicates a role of sex-hormones, most likely estrogens, in the regulation of levels of pro- and anticoagulant factors under physiologic conditions. These differences should be taken into account in daily clinical practice and may necessitate different normal ranges for men, pre- and postmenopausal women.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Chetan N Patil ◽  
Carolina Dalmasso ◽  
Rodrigo O Maranon ◽  
Huimin Zhang ◽  
Richard J Roman ◽  
...  

Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in premenopausal women, is characterized by hyperandrogenemia, metabolic syndrome and inflammation. They also exhibit elevated blood pressure (BP) but may not be treated since they do not meet the criteria for hypertension (BP>130/90 mm Hg). We have characterized a female rat model of hyperandrogenemia (HAF) using dihydrotestosterone (DHT) that mimics many characteristics of women with PCOS. In the present study we tested the hypothesis that androgen-induced upregulation of the cytochrome P450 4A2 isoform (CYP4A2) and the formation of 20-hydroxyeicosatetraenoic acid (20-HETE) in renal microvasculature contributes to the elevated BP in HAF rats. Female rats of SS.5BN consomic strain (wild type) rats and CYP4A2-/- rats on this same background were implanted with DHT (7.5mg/90d) or placebo pellets (n=5-8/grp) beginning at 6 wks of age; pellets were changed every 85 d. At 14 wks of age, rats were implanted with radiotelemetry transmitters, and mean arterial pressure (MAP) was measured for 10 days. Endogenous 20-HETE levels were measured using LC-MS in renal microvessels isolated using an Evans Blue sieving technique. DHT-treated HAF-SS.5BN rats had significantly higher MAP compared to placebo-SS.5BN (128±6 vs. 104±1 mmHg, p<0.004). In contrast, HAF-CYP4A2-/- rats had no change in MAP compared to placebo-CYP4A2-/- controls (120±4 vs 118±3 mmHg, p=NS). Endogenous 20-HETE levels in renal microvessels of HAF-SS.5BN rats were significantly increased compared to Placebo-SS.5BN (2.27±0.91 vs. 0.32±0.037 pmol/mg, p<0.01). The 20-HETE levels were lower in CYP4A2-/- than SS.5BN but DHT in HAF-CYP4A2-/- had no effect on 20-HETE levels compared to Placebo- CYP4A2-/-. These results suggest that androgen-mediated upregulation of the expression of CYP4A2 and the production of 20-HETE in renal microvessels contribute to elevated BP in HAF rats. These data also suggest that methods to attenuate 20-HETE may provide a novel therapeutic to reduce BP in women with PCOS. Work supported by NIH RO1HL66072 and PO1HL51971.


2015 ◽  
Vol 100 (3) ◽  
pp. 891-901 ◽  
Author(s):  
Christian Muschitz ◽  
Roland Kocijan ◽  
Christina Marterer ◽  
Arastoo Rahbar Nia ◽  
Gabriela Katharina Muschitz ◽  
...  

Context: The role of sclerostin as a key regulator of bone formation remains unknown after Roux-en-Y gastric bypass (RYGB) or laparoscopic sleeve gastrectomy (SG). Objectives: The study objectives were evaluation of sclerostin and Dickkopf-1 (DKK-1) serum levels after surgery and correlations with bone turnover markers (P1NP, CTX), parathyroid hormone (iPTH) and areal bone mineral density (BMD), changes at total body, lumbar spine and total hip. Design and Setting: This was a prospective observational single-center two-arm study in premenopausal women with acute adipositas over 24 months. Participants: Participants were 52 premenopausal women (40 ± 8 years, BMI 43.4) after RYGB and 38 premenopausal women (41 ± 7 years, BMI 45.7) after SG. Main Outcome Measures: Prior to surgery and 1, 3, 6, 9, 12, 18, and 24 months after surgery sclerostin, DKK-1, CTX, P1NP levels and BMD were measured. Results: Sclerostin, CTX and (to a lesser extent) P1NP increased after surgery and remained elevated during the entire study period (P &lt; 0.001). DKK-1 declined during months 3–9 (P &lt; 0.005) and then remained unchanged, serum phosphate continuously increased (P &lt; 0.001), iPTH remained within the upper normal limit. Sclerostin increases were significantly positively correlated with CTX and P1NP increases and negatively correlated with BMD loss. BMD independently declined regardless of RYGB and SG. Elevations of sclerostin, CTX, P1NP, and phosphate, but not DKK-1 and iPTH, were significant discriminating factors for BMD loss (AUC 0.920). Conclusion: Rapid and sustained increases of sclerostin, CTX, and to a lesser extent, P1NP cause an increase in bone metabolism and result in BMD loss at all skeletal sites.


1997 ◽  
Vol 272 (1) ◽  
pp. R90-R94 ◽  
Author(s):  
F. Leon-Velarde ◽  
M. A. Ramos ◽  
J. A. Hernandez ◽  
D. De Idiaquez ◽  
L. S. Munoz ◽  
...  

The objective of this study was to investigate the role of menopause in the appearance of the physiopathological sequence that leads to chronic mountain sickness (CMS) in a high-altitude female population. The females studied are 30-54 yr old (n = 152) and have permanent residence in Cerro de Pasco (Pasco, Peru; 4,300 m). The sample was divided into postmenopausal and premenopausal groups for comparison. Blood oxygen saturation (SaO2), excessive erythrocytosis [EE, measured by the level of hematocrit (Het)], peak expiratory flow rates (PEFR), and a score that represents the main signs and symptoms of CMS (CMSscore) were measured. Postmenopausal women had higher Het (50.2 +/- 4.04 vs. 47.4 +/- 4.13%, P < 0.001), lower SaO2 (81.9 +/- 4.12 vs. 84.7 +/- 3.14%, P < 0.001) and PEFR values (489 +/- 101 vs. 534 +/- 90 l/min, P < 0.02), and slightly higher CMSscore (19.1 +/- 3.37 vs. 17.9 +/- 3.48, P < 0.06) than premenopausal women. The prevalence of women with EE (EE = Hct > 56%) was found to be 8.8%. Forty-five percent of the postmenopausal subjects presented a high CMSscore (> 21), whereas only 22% of the premenopausal subjects presented this high value (P < 0.02). We can therefore conclude that menopause may represent a contributing factor for the development of CMS.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 547-547 ◽  
Author(s):  
V. H. Bramwell ◽  
K. I. Pritchard ◽  
D. Tu ◽  
K. Tonkin ◽  
H. Vachhrajani ◽  
...  

547 Background: In the early 1990’s, the role of adjuvant T in premenopausal women with EBC had not been clearly established. The efficacy of adjuvant T in hormone receptor (H) negative EBC was unclear. Methods: Eligible premenopausal women with node (N) +ve/high risk N -ve EBC, any H status, post surgery, received standard adjuvant CT (AC ×4, CMF ×6, CEF x6) then were randomized to T (20 mg/day) or P for 5 yrs. Overall survival (OS), disease-free survival (DFS) and toxicity/compliance were evaluated. Original sample size was 800 pts but based on slow accrual was reduced to 660. Mortality rate is lower than anticipated, and Data Safety Monitoring Committee approved reporting results after second interim analysis (152 deaths). Results: 1993–2000, 672 women randomized, median follow-up 8.4 yrs. For T vs P, 5 yr OS 87% vs 82% [Hazard Ratio HR 0.81 (95% CI 0.58–1.12), p = 0.19] and 5 yr DFS 78% vs 71% [HR 0.79 (95% CI 0.61–1.03), p = 0.09]. HR for OS (0.87 vs 0.78, p = 0.71) and DFS (0.79 vs 0.77, p = 0.87) were not significantly different for H +ve and H -ve tumors respectively. Compliance with T/P was suboptimal, 29% women stopping treatment within 2 yrs, and only 53% completing 5 yrs. Conclusions: Current results show only a trend towards improved DFS for premenopausal women with EBC who receive T after adjuvant CT. Other studies of similar design have shown improved DFS, but not OS, and meta-analysis may be more informative. Issues affecting results (slow accrual, improved outcomes for EBC, poor compliance, additional therapies) will be discussed. [Table: see text] [Table: see text]


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