Objective: The aim of the present study was to determine the different effects of oral estrogen therapy (ET) and transdermal ET on changes in circulating levels of cytokines and chemokines in relationship to changes in markers of inflammation in postmenopausal women with hysterectomy. Methods: Fifty-five postmenopausal women with hysterectomy were randomly assigned in open, parallel-group fashion to an oral ET group and a transdermal ET group. Serum levels of cytokines and chemokines were simultaneously measured using a multiplexed human cytokine assay. Serum concentrations of high-sensitive C-reactive protein, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1, and E-selectin were measured as vascular inflammation markers. Results: Both oral ET and transdermal ET significantly decreased serum interleukin (IL)-7 concentrations at 12 months (PZ0.020 and PZ0.015 respectively). Transdermal ET decreased serum concentrations of IL-8, monocyte chemoattractant protein (MCP)-1, and macrophage inflammatory protein (MIP)-1b (PZ0.05, PZ0.019, and PZ0.029), but oral ET increased IL-8 level (PZ0.025). There were significant differences in percentage changes in IL-8 and MIP-1b between the oral and transdermal ET groups. Oral ET significantly decreased E-selectin level after 12 months. Conclusion: Transdermal ET reduces circulating levels of IL-8, MCP-1, and MIP-1b, while both oral ET and transdermal ET reduce circulating level of IL-7.

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The influence of testosterone, androstenedione and dihydrotestosterone (DHT) on the progesterone (P₄) production by cultured porcine granulosa cells was studied in the presence or absence of gonadotropins. Porcine granulosa cells from large follicles (6-12 mm in diameter) were incubated for 2 days with 5% CO₂ in air with testosterone, androstenedione and DHT (10^-12, 10^-10, 10^-8 and 10^-6M) in the presence or absence of luteinizing hormone (LH, 10 ng/ml) or follicle-stimulating hormone (FSH, 30 ng/ml). P₄ and pregnenolone (P₅) in conditioned culture media were quantified by their specific RIAs. In the absence of gonadotropins, P₄ in media with androgens were not significantly different from controls. In the presence of LH, the addition of testosterone (10^-10, 10^-8M), androstenedione (10^-8M) and DHT (10^-8M) caused a significant 1.3- to 2.3-fold increase in P₄ over that caused by LH alone. In contrast, in the presence of FSH, testosterone (10^-12,10^-10M), androstenedione (10^-12-10^-6M) and DHT (10^-6M) reduced the levels of P₄ by 22% to 41%. The addition of androgens with LH caused a significant increase in P₅, while P₅ decreased in the presence of FSH. P₄/P₅ ratios remained unchanged in the presence of both LH and FSH. These data suggest that the P₄ production by cultured porcine granulosa cells is modulated in a paracrine or an autocrine fashion by androgens in the presence of gonadotropins, and that androgens may exert their actions partly by altering the activity of cholesterol side chain cleavage enzymes.

Human follicular fluids from normal women and from women with polycystic ovary syndrome (PCOS) were collected at various stages of the menstrual cycle, and inhibin and steroid contents were determined by rat anterior pituitary cell monolayer bioassay system and specific RIAs, respectively. Inhibin contents in viable follicles were significantly higher than those in atretic and in cystic follicles. Preovulatory and luteal phase follicles had lower inhibin levels than viable follicles in normal women. A significant inverse correlation was found between inhibin contents and androstenedione to estrogen ratios. The inhibin contents in PCOS follicles were not significantly different from those of viable follicles of normal women at the early follicular phase, but they were significantly higher than in atretic follicles. Since PCOS ovaries often contain more antral follicles than normal ovaries, it could be that this potential source of inhibin may be greater than in normal ovaries. Furthermore, 9 out of 10 follicles in any ovary of normal women are atretic and contribute less inhibin production, whereas PCOS ovaries contain many follicles capable of secreting considerable amounts of inhibin. Therefore, PCOS ovaries totally may secrete more inhibin than normal ovaries. This higher potency of PCOS ovaries to secrete inhibin along with higher serum estrogen levels may be responsible for the disparity between basal LH and FSH levels in PCOS.

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