Relationship between estradiol 16 alpha-hydroxylation and human papillomavirus infection in cervical cell transformation.

The ovarian steroid hormone estradiol and its metabolite estrone were examined in 45 normal women and 127 premenopausal women with precancerous cervical lesions. Interviews, colposcopy and cervical scrapings were performed. The mean +/- SD values for estradiol and estrone were 0.07 +/- 0.08 ng/ml and 0.06 +/- 0.02 ng/ml, respectively in normal subjects. Corresponding data in patients with cervical intraepithelial neoplasia alone or in association with human papillomavirus (HPV) infection were 0.074 +/- 0.03 ng/ml and 0.076 +/- 0.03 ng/ml or 0.080 +/- 0.03 ng/ml and 0.148 +/- 0.02 ng/ml, respectively, which revealed a significantly greater extent of estrogenic action in the latter population (p < 0.05). We considered that the presence of HPV infection probably increased 16 alpha-hydroxylation of estradiol, providing a possible link between the viral and hormonal elements, possibly having a bearing on the etiology of the disease.

Paramethasone acetate (PA): corticosteroid potency vs hypothalamic pituitary-gonadal axis.

Because paramethasone acetate (PA) suppresses basal and midcycle LH surge and blocks estrogen synthesis in the female, its possible effect upon testicular physiology was evaluated in 13 healthy men by measuring the circulating levels of FSH, LH, prolactin (PRL), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), estradiol (E2) and cortisol (C) every 4 h throughout the day, before (control) and after PA (6 mg/d/7 d). The total concentrations of each hormone, as well as the PA-induced suppressibility (measured as percent decrease in the mean 24 h plasma level) were analyzed. PA suppressed neither the basal nor circadian rhythm of T and had no effect on LH, FSH or PRL output. DHT, A, E2 were significantly reduced and the basal concentrations and circadian variations of C were abolished. PA showed a dual control on the pituitary gonadal axis and while causing a maximal suppressed adrenocortical activity it had no interference in testosterone synthesis.

Effect of paramethasone acetate upon estrogen action.

To test the antiestrogenic action of paramethasone acetate (PA), a group of five postmenopausal women were treated in two ways. For phase I, PA + mestranol, 6 mg + 80 micrograms per day for 10 days, was administered. Ten days were allowed for withdrawal of medication. For phase II, mestranol, 80 micrograms per day for 10 days, free of the glucocorticoid was administered. Daily samples of cervical mucus, vaginal cells, and peripheral blood were obtained to analyze fernlike crystallization (%), cornified pyknotic nuclei cells (%), and concentrations of ethynyl-estradiol (EE-2, pg/ml) during both phases. The fernlike crystallization pattern had a mean value of 8 +/- 0.9% for phase I, while for phase II it was 85 +/- 8% (P less than 0.05). The percentage mean value of cornified pyknotic nuclei cells of phase I was 28 +/- 5% in comparison with 53 +/- 7% observed in phase II (P less than 0.05). EE-2 mean value concentrations for phase I were 85 +/- 90 pg/ml, while for phase II they were 724 +/- 418 pg/ml (P less than 0.05). These results demonstrate that 6 mg of PA is able to compete against the estrogenic action in the parameters of the study selected.

The relationship of plasma gonadotrophins and steroid concentrations to body growth in girls.

Plasma concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH), 17 alpha-hydroxyprogesterone (17 alpha-OHP), 17 beta-oestradiol (Oe2) and progesterone (P) were measured in 352 healthy girls aged 6.0 to 15.9 years, as a function of age (CA), weight, height and calculated lean body mass (LBM) and total body fat (TBF). The earliest hormonal changes were a fall in mean plasma FSH concentrations together with a small but significant rise in plasma Oe2 well in advance of any sign of pubertal development. The next changes were a progressive rise in plasma FSH and 17 alpha-OHP concentrations without further increments in plasma Oe2; these changes corresponded to a mean body weight of 29.8 kg, a mean height of 132.0 cm (initiation of the adolescent growth spurt), a mean LBM of 24.7 kg and a mean TBF of 5.1 kg. The last events were a progressive rise in plasma LH and Oe2 and less marked in P, which occurred in association with a mean body weight of 40.0 kg, a mean height of 142.0 cm (time of peak velocity of weight and height gain), a mean LBM of 31.8 kg and a mean TBF of 9.1 kg. Significant quadratic equations were disclosed between plasma FSH and LH versus CA, weight, height and LBM, and a significant linear correlation was observed between each gonadotrophin and TBF. These results show an association, not necessarily causal, between a 'critical level' of body composition and hormonal changes at the start of the adolescent growth spurt, as well as with late hormonal events at the time of peak velocity in weight and height gain. On the other hand, LBM rather than TBF seems more closely associated with the initiation and progression of puberty.

Accumulation of ethinylestradiol in blood and endometrium of women taking oral contraceptives: the sequential therapy.

A radioimmunoassay to quantitate ethinylestradiol (EE-2) in both plasma and endometrium is described. In 29 women under sequential oral contraceptive therapy (chlormadinone acetate, 2 mg, plus mestranol, 80 microgram) for 6 to 84 months, a single blood sample and a single endometrial sample were simultaneously obtained on different days of the pseudomenstrual cycle. In 24 women under 40 years of age the mean plasma EE-2 concentrations were similar during the first (989 +/- 94 pg/ml) and the second half of the cycle (1053 +/- 186 pg/ml) (P greater than 0.05). A similar finding was observed with regard to mean endometrial EE-2 concentrations (3.55 +/- 2.1 and 5.89 +/- 1.7 microgram/gm of wet tissue, respectively). On the other hand, five women over 40 years of age had plasma EE-2 concentrations similar to those of the previous group, but the mean endometrial EE-2 concentrations was 0.9 +/- 0.6 microgram/gm of wet tissue (P less than 0.05). Although plasma follicle-stimulating hormone and luteinizing hormone did not show midcycle peak values, complete suppression of both gonadotropins was not observed. These results show that endometrium has a great ability to concentrate EE-2, and this ability seems to be greater in women below age 40 than above. Whether or not this observation might be related to the known higher incidence of endometrial cancer in women less than 40 years old who have been under chronic sequential oral contraceptive therapy cannot be disclosed from this limited number of determinations.

PIP: A radioimmunoassay to quantitate ethinylestradiol (EE-2) in both plasma and endometrium is described. In 29 women receiving sequential oral contraceptive (OC) therapy (chlormadinone acetate, 2 mg plus mestranol, 80 mcg) for 6-84 months, a single blood sample and a single endometrial sample were simultaneously obtained on different days of the pseudomenstrual cycle. In 24 women under 40 years of age, the mean plasma EE-2 concentrations were similar during the 1st (989 +/- 94 pg/ml) and the 2nd half of the cycle (1053 +/- 186 pg/ml) (P . 0.05). A similar finding was observed with regard to mean endometrial EE-2 concentrations (3.55 +/- 2.1 and 5.89 +/- 1.7 mcg/gm or wet tissue, respectively). On the other hand, 5 women over 40 years of age had plasma EE-2 concentrations similar to those of the previous group, but the mean endometrial EE-2 concentration was 0.9 +/- 0.6 mcg/gm of wet tissue (P .05). Although plasma follicle stimulating hormone and luteinizing hormone did not show midcycle peak values, complete suppression of both gonadotropins was not observed. These results show that endometrium has a great ability to concentrate EE-2, and this ability seems to be greater in women below age 40 than above. Whether or not this observation might be related to the known higher incidence of endometrial cancer in women less than 40 years old who have been under chronic sequential OC therapy cannot be disclosed from this limited number of determinations. Future study might uncover competitive effects between synthetic steroids and endogenous hormones in the endometrium.

A simultaneous assay to quantitate plasma and endometrial hormone concentrations.

A method for radioimmunoassay determination of hormones in both plasma and endometrium is presented. Total estrogen (TE) and progesterone (P) concentrations were measured simultaneously in plasma and endometrium in 59 women throughout the menstrual cycle. TE values in endometrium showed an increase of 0.45 ng/gm wet tissue weight on days 7 to 9, reaching a peak of 4.89 ng/gm wet weight at midcycle; values of 2.2 ng/gm wet weight were constant during the secretory phase. The endometrial P concentrations were 5.31 and 44.93 ng/gm wet weight during the proliferative and luteal phases, respectively. Plasma P levels during the proliferative phase were below 1 ng/ml, in comparison with values above 5.71 ng/ml during the luteal phase. The quadratic coefficients of correlation between plasma and endometrial concentrations of TE and P were 0.8 and 0.9, respectively, indicating that under such conditions modifications in the amount of circulating hormones are reflected in the target tissue. These simultaneous studies may permit further investigation of the role of circulationg hormones in local biologic phenomena.