Relationship between testosterone, estradiol and circulating PCSK9: Cross-sectional and interventional studies in humans.

BACKGROUND: Circulating PCSK9 levels are higher in women than men, in postmenopausal than premenopausal women, and in pregnant than non-pregnant women, suggesting that sex hormones may be related to PCSK9 levels. We have examined the relationship between serum estradiol (E2) and testosterone (T) and PCSK9, and the impact of E2 replacement therapy in women and T replacement and ablation therapy in men on circulating PCSK9. METHODS: We conducted a cross-sectional study to examine the correlation between serum T (in males) and E2 (in females) and serum PCSK9. We also conducted interventional studies to examine the effect of hormonal therapy on serum PCSK9 levels. RESULTS: In men, (1) serum T does not correlate with circulating PCSK9 or with LDLC in the basal state, (2) T replacement therapy does not have any effect on circulating PCSK9, and (3) T ablation therapy has mixed results. In women, (1) E2 correlates inversely with circulating PCSK9 and directly with serum LDLC, but (2) E2 replacement therapy does not have any effect on circulating PCSK9. CONCLUSIONS: We demonstrate differences between men and women in the relationship of their major sex hormones with circulating PCSK9. In men, circulating PCSK9 is not related to or affected by T except for a possible effect during T ablation therapy. In women, E2 is inversely related to circulating PCSK9 but the lack of effect of E2 therapy on circulating PCSK9 suggests that the E2-related differences in PCSK9 levels may be the result of differences in receptor-mediated PCSK9 clearance through E2-induced changes rather than production of PCSK9. The studies were registered with ClinicalTrials.gov NCT00848276.

Women's decisions about hormone replacement therapy after education and bone densitometry.

BACKGROUND: The decisions that postmenopausal women make about whether to start hormone replacement therapy may depend on the potential risks and benefits of such therapy as well as their risk for osteoporosis-related fractures. This study examined the decisions made by women at risk for osteoporosis-related fractures who were educated about hormone replacement therapy and who were given information about their bone mineral density. METHODS: The study employed a prospective cohort design. Thirty-seven post--menopausal women with risk factors for osteoporosis-related fractures were recruited from an orthopedic clinic at a teaching hospital in Hamilton, Ont. The women were given an education kit (consisting of an audio tape and a work-book) to clarify the benefits and risks of hormone replacement therapy. Two to 4 weeks later, densitometry of the hip and the lumbar spine was performed. A summary of the risks, the densitometry findings and decisions about hormone replacement therapy were given to the women's family physicians for follow-up. Outcome measures included decisions about hormone replacement therapy, as well as use of such therapy and other medications at 12 months. RESULTS: After the education component alone, 10 (27%) of the women requested hormone replacement therapy. After densitometry testing, 4 more requested hormone replacement therapy (for a total of 14 women [38%]). At 12 months, 2 (5%) of the women had been lost to follow-up. Of the remaining 35, 6 (17%) were receiving hormone replacement therapy, 7 (20%) were using bisphosphonates, and 24 (68%) were taking calcium supplements. INTERPRETATION: These preliminary findings suggest that the combination of education about hormone therapy and feedback about bone density is associated with an increase in the use of hormone replacement therapy and other preventive medications by women at risk for osteoporosis-related fractures. However, the observed increase was small and so the clinical significance must be confirmed and clarified.

Pregnancies after premature ovarian failure.

Six women who conceived after a diagnosis of premature ovarian failure are discussed. Two pregnancies occurred while the women were receiving conjugated estrogen therapy, two while taking oral contraceptives, and two women conceived spontaneously. The possible role of exogenous estrogens in sensitizing the granulosa cells to the effect of follicle-stimulating hormone and thereby inducing ovulation and conception in some women with premature ovarian failure is examined.

Plasmodium falciparum malaria mimicking autoimmune hemolytic anemia during pregnancy.

A 30-year-old woman contracted Plasmodium falciparum malaria in the first trimester of her pregnancy while taking chloroquine for malaria prophylaxis. Her illness was characterized by hemolytic anemia with IgG1 coating of the surface of the erythrocytes and IgG3 in her serum. The hemolysis subsided following treatment of the malaria infection early in the third trimester. She delivered at term an infant who had hypoplasia of the right tibia and fibula and absence of the fifth ray of the right foot. The hemolytic process was attributed to the malaria infection, and the birth defect may have been related to the antimalarial therapy in the first trimester of pregnancy.

Ultrastructural studies on testicular biopsies from eighteen cases of hypospermatogenesis.

An electron microscopic study was conducted on biopsies from 18 young hypospermatogenic patients. No signs of "tubular blockage" or "germinal disorganization" were found. The relationships between the different components of the germinal epithelium were comparable to those found in normal testes. Germ cells were often connected by cytoplasmic bridges and Sertoli cells by typical narrow junctions, which, in the case of very depleted tubules, were very extensive and of irregular outline owing to the interdigitations of the cells. Sertoli cells had normal cytologic characteristics and, contrary to the findings of other investigators in similar material, had apparently a normal amount of lipid droplets and microfilaments. In six cases, a large number of thick, banded collagen fibers substituted for the microfibrils usually found between the myoid cells in the tunica propia. The possible significance of these changes as a cause or as a consequence of the tubular changes is not yet clear.

The intrauterine contraceptive device.

This presentation brings into perspective the most recent information on intrauterine contraceptive devices. A comprehensive review of the literature is presented in a manner meaningful to the clinician. The advantages and disadvantages of this method of contraception, the problems that arise and the recommended methods of management are discussed. An updated review of the literature with regard to bleeding, pain, expulsion of the device, infection, uterine perforation and pregnancy is also presented.