Changes In Sex Steroids Research Articles

Photoperiodic Regulation of Leptin Resistance in the Seasonally Breeding Siberian Hamster (Phodopus sungorus)

Seasonal Siberian hamsters lose fat reserves, decrease body weight and leptin concentrations, and suppress reproduction on short-day photoperiod (SD). Chronic leptin infusion at physiological doses caused body weight and fat loss in SD animals but was ineffective in long-day (LD) hamsters. Using ovariectomized estrogen-treated females, we tested the hypothesis that responsiveness to leptin is regulated by photoperiod. On SD, hypothalamic neuropeptide Y, agouti-related peptide, and cocaine- and amphetamine-regulated transcript gene expression in the arcuate nucleus did not exhibit significant changes, and despite SD-induced fat loss, the catabolic peptide proopiomelanocortin was down-regulated. Food restriction of LD-housed animals caused significant reduction of fat reserves and serum leptin concentrations to SD levels, suppressed serum gonadotropins, and induced increased anabolic (neuropeptide Y, agouti-related peptide) and decreased catabolic (proopiomelanocortin, cocaine- and amphetamine-regulated transcript) gene expression in the arcuate nucleus. Leptin infusion in food-restricted animals had no effect on fat reserves or gonadotropins and did not modulate neuropeptide gene expression. Also, leptin treatment did not blunt the refeeding responses or weight and fat gain in LD-housed food-restricted animals. In conclusion, our results strongly suggest that hypothalamic responses to leptin are regulated primarily by photoperiod, rather than seasonal changes in fat reserves, sex steroids, or leptin concentrations.

Endocrine regulation and artificial induction of oocyte maturation and spermiation in basses of the genus Morone

Studying the process of final oocyte maturation (FOM) and spermiation in striped bass ( Morone saxatilis), it was determined that the failure to undergo FOM and produce normal amounts of milt in captivity was due to low plasma levels of luteinizing hormone (LH) during the spawning period. As a result, the expected changes in the plasma profiles of the steroids involved in FOM and spermiation do not take place. Based on the hormone profiles and the associated histological examinations, FOM can be separated into an early phase (germinal vesicle (gv) migration) and a late phase (germinal vesicle breakdown). The progestogen 17,20β,21-trihydroxy-4-pregnen-3-one (17,20β,21-P) was identified as the maturation-inducing steroid (MIS), but the high levels of 17,20β-dihydroxy-4-pregnen-3-one (17,20β-P) present during late FOM, suggest a role for this steroid also. In wild striped bass, spermiation was associated with increases in LH and unchanged plasma levels of 17,20β,21-P and 17, 20β-P. In culture, spermiation in both striped bass and white bass ( M. chrysops) proceeds under undetectable levels of LH, 17,20β,21-P and 17,20β-P. GnRHa-induced spermiation, however, was associated with increases in plasma LH and 17,20β-P, but not 17,20β,21-P. Treatment of females with GnRHa-delivery systems induced long-term increases in plasma LH and the appropriate changes in sex-steroid hormones. In white bass, GnRHa-delivery systems induced two successive spawns within 3 days from treatment, and in a commercial production facility induced ovulation of 90% of the females, producing 294,500 eggs kg −1 with 81% fertilization. Similarly treated striped bass underwent FOM and ovulation within 10 days after treatment, while tank spawning resulted in the production of 170,000 eggs kg −1 with 47% fertilization success. In male fish, GnRHa-delivery systems induced significant elevations of expressible milt for up to 20 days, resulting in a fourfold increase in production of spermatozoa, without affecting sperm density, motility or fertilization %.

Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle.

Antioxidant enzymes are an important part of the defence mechanisms against free radical damage. Little is known, however, about the relationship between sex steroid hormones and cellular antioxidant systems. We have investigated the effect of physiological sex steroid changes on the erythrocyte antioxidant glutathione peroxidase (GSH-Px) activity during the menstrual cycle in a population of healthy normomenorrhoic women. Prospective, controlled. Ten normally cycling women (age range: 19-28 years; mean: 23.3 years) were recruited for alternate-day blood sampling from the first day of one menstrual bleed until the first day of the subsequent menstrual phase. Plasma was analysed for LH, FSH, oestradiol (E2) and progesterone (P4) concentrations. Erythrocyte GSH-Px activity was evaluated on the same days in all subjects. Pyruvate-kinase (PK) activity, as an index of red blood cell population age, was also determined. All the women examined had a normal ovulatory cycle, as indicated by the hormone plasma pattern. Cycle length was standardized on the basis of the preovulatory E2 peak. Significant cycle phase-related changes in GSH-Px (P < 0.03) were observed, with higher GSH-Px activity levels being found from the later follicular to early luteal phase as compared to early follicular phase (chi 2 = 8.53, P < 0.001 and chi 2 = 5.54, P < 0.002, respectively). A significant positive correlation was observed between mean E2 and GSH-Px cycle-related changes (r = 0.78, P = 0.001). Conversely, no significant cycle phase-dependent variations were detected in PK. The findings support the hypothesis that physiological ovarian E2 production during the menstrual cycle may play an important role in regulating erythrocyte glutathione peroxidase activity.

Twenty-four-hour profiles of luteinizing hormone, follicle-stimulating hormone, testosterone, and estradiol levels: a semilongitudinal study throughout puberty in healthy boys.

To follow and correlate gonadotropin and sex steroid changes throughout puberty, 24-h profiles of LH, FSH, testosterone, and estradiol were taken on several occasions for between 2-9.5 yr in 12 healthy boys, aged 8.7-18.2 yr. Serum concentrations of LH and FSH were measured every 20 min, whereas testosterone and estradiol were measured every 2-4 h during the 24-h period. The prepubertal boys (Tanner stage 1) were subdivided into two groups: Pre 1, with a testicular volume of 1-2 mL, and Pre 2, with a testicular volume of 3 mL. Pubertal stages were classified, according to testicular volume, as early puberty (pubertal stage 2; 4-9 mL), midpuberty (pubertal stages 3-4; 10-15 mL), and late puberty (pubertal stage 5; > or = 16 mL). Mean levels of LH and FSH increased with pubertal development, although the increase in LH was greater than that in FSH. These increases were due to elevated basal levels of LH and FSH as well as to increases in the number of peaks and the peak amplitudes of LH. No diurnal rhythm was found in boys at stage Pre 1. Thereafter, a clear diurnal rhythm appeared for LH, and later in puberty, an ultradian rhythm was superimposed, as shown by time-sequence analyses. A diurnal rhythm also existed for FSH, but was much less marked than that for LH despite a clear covariation between LH and FSH, as shown from cross-correlation studies. Testosterone also showed diurnal variations from the late prepubertal stage, followed by increasing levels during both day and night in puberty. We conclude that during puberty, gonadotropin levels rise differently for LH and FSH, which may be due to the development of differences in feedback mechanisms. Despite covariation between LH and FSH, only LH showed a clear diurnal variation. In parallel, nocturnal variations in testosterone and estradiol were found. Changes in mean levels of LH, testosterone, and estradiol as well as their mean daytime and nighttime levels follow each other from the prepubertal stages to late puberty.

Changes in Plasma Sex Steroids in Females of Two Sympatric Leptodactylus from Subtropical South America

Changes in Plasma Sex Steroids in Females of Two Sympatric Leptodactylus from Subtropical South America

Urinary biochemical markers for bone resorption during the menstrual cycle

In order to analyze the effects of serum ovarian steroid hormones on bone metabolism during the menstrual cycle, we have measured urinary levels of type I collagen cross-linked N-telopeptide (NTx), hydroxylysylpyridinoline (HP), lysylpyridinoline (LP). and hydroxyproline (OH-Pr) in nine healthy Japanese women, aged 22-43 years, with normal ovarian function. The cycles were synchronized by serum LH peaks, and follicular and luteal periods were normalized by lengths. Serum gonadotropins and ovarian sex steroids showed significantly different cyclic variations during the menstrual periods. Urinary NTx remained unchanged during the early follicular period, showed a rise during the mid- and late follicular period, and a fall during the mid- and late luteal periods. There were significant differences in NTx levels between early follicular period and midfollicular period (P < 0.01), or late follicular period (P < 0.05), and between early luteal period and late luteal period (P < 0.05). The levels of HP and LP showed a rise during the early an midfollicular periods and a fall during the midluteal period. The correlation of NTx with urinary OH-Pr was better than with urinary HP or LP (r = 0.731 versus r = 0.449 or r = 0.634). This variation suggests that cyclic changes in serum ovarian sex steroids might modulate bone resorption markers during the menstrual cycle.

Differential changes in serum concentrations of androgens and estrogens (in relation with cortisol) in postmenopausal women with acute illness.

Previous studies of adrenal androgens and estrogens in critical illness were limited by measuring only selected sex steroids and by including men (who have confounding simultaneous changes in gonadal steroids). We evaluated relationships between changes in serum levels of cortisol (F), androgens, estrogens, and gonadotropins in 20 postmenopausal women with acute critical illness to determine if changes in adrenal androgens and estrogens paralleled gonadal axis suppression or adrenal stimulation. Two patterns of changes in sex steroids were observed. Admission serum levels of androstenedione (delta 4-A), estradiol, and estrone, like F, were increased compared to healthy controls (P < 0.0001). delta 4-A and estrone then decreased toward normal by day 5 in parallel with cortisol (r = 0.56 and 0.60). In contrast, admission serum dehydroepiandrosterone (DHEA) and DHEA-sulfate (DHEA-S) were not elevated and testosterone (T) was decreased in our patients compared to controls (P < 0.0005) in parallel with serum gonadotropin levels. Serum levels of DHEA and T continued to decrease by day 5 in parallel with gonadotropins. We conclude that in agonadal patients with acute critical illness, serum levels of DHEA-S and T are selectively decreased in relation to F, delta 4-A, and estrogens. The decreased serum T levels suggest inhibition of 17 beta-OH-dehydrogenase and/or increased aromatization to estradiol. The marked increase in serum estrogen levels also suggests increased aromatization. The absence of increases in DHEA and DHEA-S suggest enhanced activity of 3 beta-hydroxysteroid dehydrogenase and/or inhibition of C17,20-lyase activity of P-450c17. The clinical significance of this marked increase in the ratio of estrogens to androgens in acute illness requires further investigation.

Effect of the aromatase inhibitor, 4 hydroxyandrostenedione, on the endotoxin-induced changes in steroid hormones in male rats

The increase in circulating estrogen concentrations that follows injection of Escherischia coli endotoxin (Endo) may be due to increased aromatase activity. We have therefore analysed the effect of the aromatase inhibitor, 4 hydroxyandrostenedione (4OHA) on the steroid hormone response of male rats, particularly the dramatic increase in estrogens and decrease in androgens, induced by Endo. The concentrations of corticosterone (B), progesterone (P4), 17α hydroxyprogesterone (17αOHP4), androstenedione (Δ4), testosterone (T), estrone (E1) and estradiol (E2) were determined 2 hours after injection of increasing doses of 4OHA with and without Endo. The increase in serum estrogen concentrations and drop in serum androgen levels in response to Endo were blocked by a single dose of 4OHA. The effect of 4OHA appeared to be dose dependent. Low doses (30 mg/kg and 50 mg/kg) induced significant changes in the estrogen and androgen responses, but the high dose (100 mg/kg) blocked all changes in sex steroids induced by Endo. 4OHA did not alter the Endo-induced changes in other steroids.

Sex steroid changes in porcine cystic ovarian disease

Ten sex steroids were measured in the peripheral serum and ovarian follicular fluid of female pigs with or without cystic ovarian disease. In general, progestin, especially progesterone, accumulated excessively in the fluid contained in cystic compared with normal follicles. Nonluteinized cystic follicles contained up to four times the progesterone concentration found in large normal preovulatory follicles. Levels of this steroid increased with luteinization of cystic follicles to as much as 10 times those found in large preovulatory follicles. In contrast, the concentration of follicular fluid androgens and estrogens in cystic follicles were, at best, barely detectable (5 to 10 pg/ml). These results are indicative of a steroidogenic blockade in the conversion of C21 progestin to C19 androgens and C18 estrogens in the cystic follicles. In spite of an enormous accumulation of follicular progestin and subnormal concentration of androgens and estrogens, circulating levels of these hormones in pigs bearing cystic ovaries were in the normal range for cycling sows. Clearly, the hormonal abnormalities in the cystic follicles are not reflected in the serum profiles of these steroids.

Changes in plasma vitellogenin, sex steroids, calcitonin, and thyroid hormones related to sexual maturation in female brown trout ( Salmo trutta)

Female brown trout ( Salmo trutta) from a wild strain (Baltic sea trout) and a cultured strain were sampled individually for blood plasma at regular intervals during the period around final sexual maturation. The plasma samples were analyzed for vitellogenin (VTG), estradiol-17β, testosterone, 17α,20β-dihydroxy-4-pregnen-3-one (17,20β-P), calcitonin, triiodothyronine (T 3), thyroxine (T 4), and total and free plasma calcium. In the wild fish, VTG, estradiol-17β, and testosterone peaked 30 days before ovulation, while 17,20β-P had a sharp peak at ovulation. Both T 3 and T 4 declined at the beginning of the sampling period, reached minimal levels 30 days before ovulation, and rose sharply at the time of ovulation. Calcitonin levels were elevated during final maturation. Total plasma calcium correlated with plasma VTG levels. In the cultured strain, sampling was started 2 weeks before ovulation. The levels of VTG, estradiol-17β, and testosterone decreased throughout the sampling period. 17,20β-P and calcitonin concentrations were high during the period close to ovulation. Plasma thyroxine remained at basal levels in cultured trout. The discrepancies observed between wild and cultured females may be due to differences in stress susceptibility, environmental conditions, life cycles, or to genetic divergence between the strains.

Annual changes in serum sex steroids in male and female black (Ursus americanus) and polar (Ursus maritimus) bears.

The adaptation of black and polar bears to their environments is proportional to the severity of climate and food restriction. Both black and polar bears mate during the spring, despite differences in their recent metabolic state. Reproductive activity in black bears follows 4 mo of torpor, whereas reproduction in polar bears occurs prior to torpor. The goals of this study were to measure the annual changes in serum sex steroids in male and female black and polar bears, and to determine if changes in serum levels of these steroids were associated with metabolic condition or photoperiod. Serum testosterone (T) concentrations were elevated during spring in black and polar bears. Moreover, this increase in serum T in polar bears during spring was correlated with age and testis size. Serum progesterone (P4) concentrations increased in pregnant polar bears in fall coincident with the time of expected implantation. No increases in serum P4 were observed in nonpregnant black and polar bears. Serum estradiol (E2) was elevated in nonpregnant and pregnant polar bears 2 mo prior to the time of expected implantation. We found that serum sex steroids measured in black and polar bears change independent of torpor. Therefore, our results suggest that photoperiod may be a more important regulator of serum steroid levels and reproduction than metabolic condition.

Estrogen, progesterone, prolactin, prostaglandin E2, prostaglandin F2α, 13,14-dihydro-15-keto-prostaglandin F2α, and 6-keto-prostaglandin F1α gradients across the uterus in women in labor and not in labor

Before or during labor in humans, changes in peripheral levels of estrogen and progesterone are not evident. Local alterations of estrogen, progesterone, and prolactin concentrations may be present and be accompanied by prostaglandin changes. The purpose of this study was to investigate the differences in concentrations of these hormones across the uterus and to evaluate their interrelationships in patients at term gestation with and without labor. Blood samples were obtained from a radial artery and a uterine vein in 22 women without and in 10 with labor. The difference between levels in the two blood vessels was designated as the gradient. Neither levels nor gradients were different between the two groups for estrone, estradiol, estriol, progesterone, or prolactin. The plasma levels of prostaglandin F2 alpha, 13,14-dihydro-15-keto-prostaglandin F2 alpha, and prostaglandin E2 were significantly increased in labor. Prostacyclin levels, as indicated by the 6-keto-prostaglandin F1 alpha metabolite, were not altered. The gradients for prostaglandin F2 alpha and E2 were significantly increased in labor. The results of the study also suggested that, in gestation at term, serum prolactin is produced mainly by the pituitary and that estrone may originate from peripheral conversion of estradiol. We conclude that in humans prostaglandin gradients of the E and F groups are increased in labor. These increases are not associated with changes in sex steroids or prolactin. Prostacyclin metabolite gradients also appear not to be altered in labor, suggesting that some prostaglandins are selectively increased in early labor either by enhanced production or decreased metabolism or both.

Protein degradation and protease activity of chum salmon (Oncorhynchus keta) muscle during spawning migration

Sarcoplasmic protein content decreased significantly and myosin heavy chain was degraded gradually during spawning migration of chum salmon (Oncorhynchus keta).Acid and neutral proteinase activities increased significantly during spawning migration. These proteinase activities were higher in females than in males. High levels of acid proteinase were not caused by the injury of lysosomal membranes. Considering the physiological states of chum salmon, neutral proteinase activity might be related to the degradation of muscle protein.As the changes in serum sex steroids were similar to those in the protease activities during spawning migration, it was considered that high levels of protease activity during spawning migration were closely related to the serum levels of androgens.

Early menopausal changes in bone mass and sex steroids.

Eighty-four healthy perimenopausal and early postmenopausal women were divided into four groups: group A, those with slightly irregular menstrual periods and plasma FSH below 40 mIU/ml; group B, those with irregular periods and FSH above 40 mIU/ml; group C, those whose last menstrual period was within 1 yr of study; and, group D, those whose last menstrual period was between 12 and 55 months before the study. Plasma concentrations of estrone and estradiol progressively decreased in groups B, C and D compared to those in A in parallel with a decrease in the production rates, and FSH and LH were significantly increased. There was little change in the concentration of androstenedione or testosterone. Vertebral bone mass was significantly decreased in groups B, C, and D compared to that in A, and radial bone mass was decreased in group D. There was a significantly positive correlation between plasma estrone and estradiol and bone mass at both the radius and vertebra. Increased bone remodeling was suggested by increases in serum calcium and bone gla protein. These data suggest that bone loss, at least from the spine, may begin before menses cease and is correlated with decreases in estrogen production and increases in bone remodeling.

Changes in beta-endorphin-like immunoreactivity in pituitary portal blood during the estrous cycle and after ovariectomy in rats.

beta-Endorphin-like immunoreactivity (beta-EP-LI) was measured by RIA in plasma collected from pituitary portal vessels of rats at various times in the estrous cycle and after ovariectomy. There were no appreciable differences between the mean beta-EP-LI concentration either in the afternoon (1500-1700 h) of estrus (4.1 +/- 1.5 ng/ml) or on diestrous days 1 (4.1 +/- 1.3 ng/ml) or 2 (5.4 +/- 1.5 ng/ml). The concentration increased slightly (6.7 +/- 1.3 ng/ml) but not significantly in the early afternoon (1400-1500 h) of proestrus. The concentration of beta-EP-LI then fell to 0.5 +/- 0.1 ng/ml at 1700-1800 h on proestrus, a level significantly lower than at any other time of the cycle. Portal plasma beta-EP-LI was also low (1.9 +/- 0.5 ng/ml) in animals ovariectomized for 3 weeks. After gel filtration of the portal plasma extracts, most of the beta-EP-LI eluted in the same position as synthetic beta-EP. Dilution of portal plasma produced a displacement curve parallel to that of beta-EP and hypothalamic extract. These results indicate that the secretion of hypothalamic beta-EP into the blood of pituitary portal vessels changes during the estrous cycle, possibly due to cyclic changes in sex steroids.

Influence of sex steroids on the catecholamine biosynthesis in chromaffin tissue from rainbow trout, Salmo gairdneri

The in vitro activities of dopamine-β-hydroxylase (DBH) and phenylethanolamine- N-methyl transferase (PNMT) were determined in the chromaffin tissue (head kidney) of sex steroid-treated rainbow trout, Salmo gairdneri. In addition, the DBH and PNMT activities were measured in fish at different sexual states. Steroid treatment increased the wet weight of the head kidney, while both DBH and PNMT activities decreased. Although no sex difference in the enzyme activities was detected, a possible correlation between DBH and PNMT activities and increased GSI values was indicated. The presented data suggest that changes in sex steroids during development may affect the catecholamine synthesis in the chromaffin tissue in S. gairdneri.

Annual and Daily Changes in Plasma Gonadotropin and Sex Steroids in Relation to Teleost Gonad Cycles

Abstract Long-term (annual and seasonal) variations in plasma concentration of reproductive hormones (maturational gonadotropin GTH and sex steroids) have been studied in relation to the gonad cycle in some teleosts. Plasma GTH concentrations are low and increase only gradually during the major part of gonad development (vitellogenesis, spermatogenesis) but increase sharply towards the end of gametogenesis–that is, around the time of oocyte maturation and ovulation and before the start of spermiation. In females, plasma concentrations of 17β-estradiol and estrone rise continuously during vitellogenesis. In salmonids, after a decrease in 17β-estradiol concentration starting at the end of the vitellogenesis, there is a small peak in testosterone concentration followed by a strong transient rise in 17α-hydroxy-20β-dihydroprogesterone, which induces oocyte maturation. The concentrations of testosterone and 11-ketotestosterone rise during spermatogenesis. Maximal concentrations of 11-ketotestosterone were reco...

Seasonal and stress related changes in plasma gonadotropins, sex steroids, and corticosterone in the bullfrog, Rana catesbeiana

Studies of seasonal gonadal cycles combined with direct measurements of plasma levels of the two gonadotropins (FSH and LH), several gonadal steroids (estrogen, E; progesterone, P; testosterone, T; and 5α-dihydrotestosterone, DHT), and the interrenal steroid corticosterone (B) were made in male and female bullfrogs in central California over a 5-year period (between 1976 and 1981). During the course of these studies, we discovered that levels of plasma gonadotropins and steroids are highly labile and particularly sensitive to the effects of captivity, especially in males. In animals captured and sampled repeatedly in the field over a 3-day period, hormone levels remained constant, but if held in collecting sacks, gonadotropin and gonadal steroids began to drop within 2–4 hr and usually reached “baseline” levels within 20 hr. This effect was apparent in all seasons, except occasionally in early spring when hormone levels dropped by only about half. Hormone levels were also generally depressed by the time commercially collected frogs reached local supply houses. Plasma B increased within 30 min of capture and remained high for days in captive animals. Blood samples taken from several hundred animals at the time of capture reveal pronounced seasonal cycles in all hormones measured. These changes are discussed in connection with other gross changes in gonadal condition and with regard to possible interactions among gonadotropins and steroids. Both sexes show a general elevation of hormone levels in spring and early summer, but the sexes differ somewhat both in timing and in magnitude of the changes, as well as in the nature of the dominant steroids. Pronounced “surges” in gonadotropins are evident around the time of gamate release in both sexes, but the temporal pattern of these surges is not the same for ovulation and spermiation; an elevation in plasma P is associated with the periovulatory surge in gonadotropins. Results were not entirely consistent with expectations of pituitary-gonadal relationships. Levels of plasma gonadotropins and steroids did not show the reciprocal relationship expected from a simple negative feedback between gonadal and pituitary secretion, nor did changes in gonadotropins and gonadal activities show the consistent positive correlation expected from a direct dependence of gonadal function on circulating gonadotropins. In females, plasma T, but not E, correlated with ovarian growth. Plasma T in females reached much higher levels than in males, but DHT was higher in males. Androgens were generally elevated during the period of sexual activity in males, but absolute levels did not correlate well with individual differences in sexual behavior. Thus, seasonal changes in testicular and ovarian activities cannot be accounted for solely by seasonal cycles in circulating gonadotropin levels.

Effect of sex steroids on beta-endorphin in hypophyseal portal blood.

Previous studies in female monkeys have shown that beta-endorphin (beta-EP) of hypothalamic origin is present in high concentrations in the hypophyseal portal blood and declines at the time of menses and after ovariectomy. In this study we have examined the effects of estradiol and progesterone replacement on portal blood beta-EP in ovariectomized monkeys. After acute iv administration of estradiol (2 micrograms), beta-EP did not rise from previously low levels (less than 133 pg/ml) over the ensuing 3 h. After chronic estradiol replacement for 3 weeks, portal beta-EP was detectable in 2 of 4 ovariectomized monkeys, with peak values of 341 and 733 pg/ml, respectively. When progesterone as well as estradiol were replaced chronically, high levels of beta-EP, [1610 +/- 192 (SE) pg/ml] were measured in all 13 portal blood samples collected from 4 ovariectomized monkeys. The majority of the beta-EP immunoactivity in these samples eluted from a Sephadex G-50 column in the same position as synthetic human beta-EP. Cation exchange chromatography showed that the majority of immunoactive beta-EP in portal plasma appeared to be nonacetylated beta-EP (1-31). We conclude that ovarian steroids are necessary for the release of hypothalamic beta-EP into portal blood and suggest that cyclic changes in sex steroids may affect anterior pituitary function in part via a mechanism involving hypothalamic beta-EP.

Changes in unbound sex steroids and sex hormone binding globulin-binding capacity during oral and vaginal progestogen administration

Four groups of five cycling women each received either a contraceptive vaginal ring containing a combination of either levonorgestrel or norethindrone with estradiol or oral contraceptives containing a combination of either dl-norgestrel or norethindrone with ethinyl estradiol. Pretreatment as well as 2- and 7-week treatment serum samples were assayed for sex hormone binding globulin-binding capacity (SHBG-BC), estradiol, non-SHBG-bound estradiol, testosterone, and non-SHBG-bound testosterone, d-norgestrel, non-SHBG-bound d-norgestrel, and norethindrone. SHBG-BC was significantly increased in the norethindrone oral contraceptive group, unchanged in the norgestrel oral contraceptive group, and significantly reduced in both contraceptive vaginal ring groups. These findings indicate that the positive effect of oral ethinyl estradiol on SHBG-BC offsets the suppressive effects of d-norgestrel on SHBG-BC, while the estradiol in the d-norgestrel or norethindrone contraceptive vaginal rings is insufficient to alter the suppressive effect of d-norgestrel or norethindrone on SHBG-BC. In contrast, the ethinyl estradiol in the norethindrone oral contraceptive overcame the suppressive effect of norethindrone on SHBG-BC, resulting in a significantly increased SHBG-BC level. Although total circulating estradiol was significantly decreased in the contraceptive vaginal ring groups, the percentage of unbound serum estradiol was significantly increased in both contraceptive vaginal ring groups and significantly reduced in the norethindrone oral contraceptive group. Although total circulating testosterone was significantly reduced only in the norgestrel oral contraceptive group, the percentage and mass of unbound testosterone were significantly decreased in the norethindrone oral contraceptive group, while the percentage of unbound testosterone was significantly reduced in the norgestrel oral contraceptive group and significantly increased in the norethindrone contraceptive vaginal ring group. As levels of unbound (biologically active) steroid differ markedly from levels of total steroid, it is essential to measure levels of non-SHBG-bound estradiol and testosterone in order to detemine effects of steroidal contraceptives on physiologically active circulating endogenous steroids.