Mean Estradiol Levels Research Articles

Estradiol/progesterone-releasing vaginal rings for hormone replacement therapy in postmenopausal women

In order to investigate whether vaginal rings delivering estradiol and progesterone could prevent endometrial hyperplasia and relieve climacteric symptoms ,two variants of rings were used in 20 postmenopausalwomen with intact uteri for 4 months. One ring designated as PI-002 (n = 8) delivered in vitro estradiol 160 μg/day and progesterone 20 mg/day ,while the other (PI-003; n = 12) deliveredthe same dosage of estradiol but only half the progesterone (10 mg/day). Serum estrone ,estradiol and progesterone were measured at pretreatment ,weekly for 4 weeks ,and then monthly for 4 months. The incidenceof hot flushes ,frequency of night sweats ,mood scores ,vaginal discharge and bleeding profiles were recorded. Endometrial thickness was monitored by ultrasonography. The mean estrone level was 50 pg/mlfor 16 weeks. The mean serum estradiol level was 75 pg/ml for the first 4 weeks and gradually decreased to 50 pg/ml at 16 weeks. The mean progesterone level with the PI-002 ring was 5 ng/ml for the first4 weeks and decreased to 3.5 ng/ml at 16 weeks. With the PI-003 ring ,the mean progesterone level was initially 3.5 ng/ml and then decreased to 2.5 ng/ml thereafter. Significant decreases in the incidenceof hot flushes and night sweats as well as a striking improvement in mood scores were noted as early as 2 weeks after insertion. Three of the 20 women discontinued the treatment ,owing to ring expulsion.Increased vaginal discharge was observed with both rings in the first 6 weeks. Vaginal bleeding was more frequently apparent among users of the PI-002 ring ,although bleeding and spotting were confinedto the first 6 weeks. Ultrasonographic monitoring of the endometrium constantly revealed a thickness of < 3 mm for both variants throughout use for 16 weeks. An estradiol/progesterone-releasing vaginalring is a potential alternative to long-term hormone replacement therapy with minimum attention required. It provides effective protection against endometrial hyperplasia.

Basal endocrine status in African dietary iron overload.

Endocrine disturbances, notably diabetes, have been well described as a complication of iron overload due to hereditary hemochromatosis and beta-thalassemia. Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis has also been well documented. The pattern of iron loading in African iron overload with saturated transferrin is similar to that seen in hereditary hemochromatosis. In addition, many symptoms ascribed to pituitary dysfunction are common to both conditions. The present study was undertaken to assess whether a similar pattern of endocrine dysfunction occurs in African iron overload. Thirty subjects with African iron overload and transferrin saturation >50%, plus 30 age and sex matched normal controls were studied. An iron profile, fasting plasma glucose, cortisol, DHEA-S, LH, FSH, growth hormone, prolactin, TSH, and FT4 levels were measured in all 60 subjects as well as testosterone in the males and estradiol in the females. Iron loading in the subjects with increased transferrin saturation ranged from moderate to severe. No significant differences were found in the mean testosterone, estradiol, LH, DHEA-S, growth hormone, prolactin, or TSH levels between the subjects and normal controls. In female subjects, although within the normal range, the mean FSH level was significantly higher, probably due to their being somewhat older and in a more advanced stage of menopause than the control females. Mean cortisol concentrations were increased in both genders in the patient group, significantly so in the females; however, values were within the reference range. We conclude therefore that there appears to be no major impairment of endocrine function in the basal state in African iron overload subjects with moderate to severe degrees of iron loading.

Cholesterol-lowering medication, cholesterol level, and reproductive hormones in women: the women’s ischemia syndrome evaluation (WISE)

Purpose Reproductive hormones such as estrogen, progesterone, and testosterone are synthesized from a common cholesterol precursor pathway. We hypothesized that use of statins and the resultant lower blood lipoprotein levels would be associated with lower reproductive hormone levels in women. We also sought to evaluate this association, independent of statin use, particularly among premenopausal women of childbearing age. Methods We enrolled 453 (114 pre-, 30 peri-, and 309 postmenopausal) women with coronary risk factors (mean [± SD] age, 58 ± 13 years) who were undergoing coronary angiography for suspected ischemia at four academic medical centers. Blood lipoprotein levels (total cholesterol, triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol) and serum reproductive hormone levels (estradiol, bioavailable estradiol, estrone, progesterone) were measured. Results Use of statins was associated with lower lipoprotein levels, but not lower reproductive hormone levels, in all women. Mean estradiol levels were not significantly lower among premenopausal women with very low LDL cholesterol levels compared with women with higher LDL cholesterol levels (estradiol: 71 ± 52 pg/mL vs. 88 ± 67 pg/mL, P = 0.32). Conclusion Among women undergoing coronary angiography for suspected myocardial ischemia, the use of statins, or lower cholesterol levels, are not associated with significantly lower levels of reproductive hormones.

Die ovarielle Stimulation mit Follitropin alfa für die Ovulationsinduktion - eine Standortbestimmung

Objective: Objective: Follitropin alpha recombinant follicle stimulating hormone (r-hFSH) is identical to endogenous FSH. Compared with urinary FSH, the recombinant form has high batch-to-batch consistency and purity and is more effective, r-hFSH can be self-administered. We conducted a post-surveillance study on the efficacy of r-hFSH for ovulation induction cycles. Methods: We documented 1371 ovulation-induction cycles in 728 patients (328 cycles in 204 women with timed intercourse and 993 cycles in 524 patients with intrauterine insemination). Results: The average duration of stimulation was 10 days with an average cumulative r-hFSH dose of 1050 IU (14 ampoules of 75 IU). 32.5% of the cycles achieved one, 26% two, and 13% three follicles ≥ 15 mm. Only 15 cycles were cancelled because of risk for ovarian hyperstimulation. In 94 cycles ovulation was triggered with an alternative to hCG or was spontaneous. The mean estradiol level on the day of hCG administration was 473 pg/mL (1736 pmol/L). The clinical pregnancy rate was 19% with an abortion rate of 14.5%. Severe ovarian hyperstimulation developed in 14 cycles (1.0%). Conclusion: r-hFSH for induction of ovulation and with subsequent timed intercourse or intrauterine insemination results in good pregnancy rates. Low-dose protocols might reduce the rate of multiple pregnancies.

Mechanism of action of levonorgestrel contraceptive implants

Levonorgestrel implants release constant low doses of the hormone over a period of several years. The levonorgestrel exerts its contraceptive action by causing changes in the cervical mucus ,by inhibiting ovulation and by promoting ovulatory dysfunction. Cervical mucus becomes viscous and scanty. Postcoital studies and sperm penetration tests in vitro have shown that few sperm penetrate the mucus and that this effect persists ,even in cycles with high endogenous estradiol production. Ovulation is inhibited in over 85% of the cycles in the first year of use ,when the release rate of levonorgestrel is highest. The percentage of ovulation inhibition decreases to near 65% of the cycles in years 2 and 3 ,while luteal activity occurs in around 50% of the cycles in the last 2 years of use. However ,in these apparently ovulatory cycles ,a dissociation of the normal ovulatory process has been observed. The peak of follicle stimulating hormone present in non-users does not occur ,and the luteinizing hormone peak is blunted and of short duration. It is known that the mid-cycle gonadotropin surge plays a major role in the maturation of the oocyte; it is therefore possible that ,due to this inadequate gonadotropin surge ,the oocyte may not be capable of fertilization in the event of follicular rupture. Luteal phase defect has also been reported. Ultrasound evaluation of follicular activity during levonorgestrel implant use has shown that luteinization of unruptured follicles occurs in nearly 30% of the cycles with luteal activity. Persistent follicles are also a common observation among implant users. Since low-dose progestins do not completely inhibit the gonadotropin stimulus ,follicular growth occurs. However ,the positive feedback of estradiol on the mid-cycle gonadotropin surge is frequently blocked ,thus preventing follicular rupture. This dominant follicle remains functional for about 21 days ,but the anatomic structure remains echographically visible for around 1-2 months before spontaneously disappearing. Hypoestrogenism is not a concern in women with levonorgestrel implants since mean estradiol levels in samples taken twice weekly for 4-5 weeks were not significantly different in women using implants from those acting as controls.

Management of women with polycystic ovary syndrome who experienced premature luteinization during clomiphene citrate treatment

Objective: To determine the preferred treatment modality in patients with PCOS who experienced premature luteinization during CC treatment. Design: Prospective randomized study. Setting: Tertiary medical center. Patients: Twenty-two infertile women with PCOS demonstrating premature luteinization during at least two consecutive CC cycles. Interventions: Randomized induction of ovulation either with FSH alone or with GnRH agonist combined with FSH for a single treatment cycle. Main Outcome Measures: Premature luteinization was defined as serum progesterone >1.5 ng/mL before hCG administration. Results: Premature luteinization occurred in eight of the 10 patients (80%) in group A and in two of the 12 patients in group B (16.6%). This result corresponds to the higher mean (±SD) progesterone level present in group A patients as compared to those in group B (2.0 ± 1.2 ng/mL vs. 1.2 ± 0.6 ng/mL, P=0.03). No pregnancies were achieved in group A, whereas the pregnancy rate per cycle observed in group B was 33.3% (4/12). On the day of hCG administration, the maximum mean (±SD) estradiol level was significantly lower ( P<0.0001) in group A (210.6 ± 37.9 pg/mL) than in group B (600.3 ± 253.8 pg/mL). The treatment duration and the number of FSH ampules used did not differ between the groups. Conclusions: Pituitary desensitization with GnRH analog in combination with FSH is superior to FSH-only treatment in PCOS patients who demonstrate premature luteinization during CC treatment.

Gonadal Source of Testosterone Metabolites in Urine of Male Cotton-Top Tamarin Monkeys (Saguinus oedipus)

Examining gonadal function in the small excitable cotton-top tamarin monkey (Saguinus oedipus) requires noninvasive sampling techniques. Two studies were performed to identify the quantifiable urinary metabolites of testosterone in cotton-top tamarins and which of the measurable metabolites would best reflect a gonadal source of testosterone secretion. In the first study, we injected unlabeled testosterone i.m. in males at either 500-ng or 1-μg levels. Urine samples were analyzed for androgens and estrogens. Testosterone and dihydrotestosterone (DHT) increased significantly following the injections in test males but not in control males. No significant increases in androstenedione occurred. Mean levels of estradiol and estrone did not consistently increase during the 5 days following injection. In the second study, a gonadotropin-releasing hormone antagonist, Antide, was used to block LH stimulation of gonadal steroidogenesis. Males given Antide at either a 6 mg/kg dose or an 18 mg/kg dose showed significantly lower levels of urinary LH than controls. At the higher Antide dose, testosterone levels were significantly reduced during weeks 1 and 2 posttreatment, whereas DHT levels significantly declined during the 2nd week posttreatment. Estradiol levels were highly variable prior to treatment but decreased significantly following treatment, whereas estrone levels remained variable throughout. These results indicate that measurement of urinary testosterone and possibly DHT reflect gonadal function in male cotton-top tamarins. Other sources of urinary estrogens may occur for the male cotton-top tamarin, but these data suggest that a substantial part of urinary estradiol is from gonadal sources, whereas urinary estrone appears to be mainly from extragonadal sources.

Estradiol and nitric oxide in men over 50 years of age.

We measured the circulatory levels of nitric oxide and estradiol in men over 50 years with estrogenisation findings. We investigated relation between nitric oxide, which is the principal signal for relaxation of vascular smooth muscle cells, and estradiol levels in serum in men over 50 years with estrogenisation. This study included 14 men with (group 1) and 20 without estrogenisation findings (group 2). Mean nitric oxide and estradiol levels were found to be significantly lower in group 2 than group 1. Group 2 had lower levels sex-hormone binding globin and higher both systolic and diastolic blood pressure values than group 1. There was a significant correlation between nitric oxide and estradiol in esrogenisation group.

Estradiol-delivering vaginal rings for hormone replacement therapy

Objectives: This study was undertaken to determine the relief of climacteric symptoms by vaginal rings delivering estradiol and to monitor estrogen levels. Study Design: Rings releasing in vitro either 60 or 140 μg/d estradiol were used by 35 women who had undergone hysterectomy for each dose level. Hot flash and night sweat incidences, vaginal conditions, and complaints were recorded at clinic visits pretreatment and at 1 week, 2 weeks, 1 month, and monthly thereafter through 6 months. Serum samples were assayed for estradiol, estrone, and estrone sulfate. Results: Hot flash incidence was reduced by about 80% with either ring. Vaginal conditions and mood were improved. Fourteen of 70 women discontinued ring use during the trial, 5 because of ring expulsions. Mean (±SD) estradiol levels were 123 ± 48 and 307 ± 93 pmol/L for the low and high dosage levels, respectively. Mean estrone levels exceeded estradiol levels by 1.7-fold for the higher dosage ring and 2.6-fold for the lower dosage ring. Increases in estrone sulfate concentrations were many times greater than those of estradiol or estrone. Conclusions: Vaginal rings are an acceptable method of delivery for periods of ≥6 months of doses of estradiol that reduce vasomotor symptoms and improve vaginal conditions. There was little difference in these responses between the 2 dosage levels. (Am J Obstet Gynecol 1999;181:1400-6.)

OESCLIM®: an advanced delivery system for HRT

Aims: Transdermal estradiol offers a number of advantages over traditional oral routes of hormone replacement therapy (HRT) because it is not subject to the hepatic first-pass effect. However, transdermal systems need to balance adhesion, tolerability, and flux if they are to be effective. OESCLIM® is a transdermal 17-β estradiol HRT system designed to address the problems of conventional transdermal patches and offer optimal adhesion and tolerability in an effective HRT system. This paper reviews some of the data on OESCLIM® with reference to its delivery system. Results: The innovative technology used in OESCLIM® results in a smooth pharmacokinetic profile throughout the 3–4 day application period. In recent pharmacokinetic studies, OESCLIM® 50 provided a more consistent release of hormone than Estraderm TTS® 50 and higher mean estradiol levels than Systen® and Vivelle®. This smooth pharmacokinetic profile is also maintained whether OESCLIM® is attached to different body sites. The local skin tolerability of OESCLIM® is good. One study reported that OESCLIM® 50 caused less than half the number of skin reactions as Estraderm TTS® 50 (4.2% compared to 9.5%). OESCLIM® has also been shown to have fewer detachments than Estraderm TTS® (6% compared to 11%). Both differences were statistically significant ( P<0.001). A study has shown OESCLIM® to be as effective as Estraderm TTS® at reducing vasomotor symptoms even in highly symptomatic women. Conclusion: OESCLIM® is a very good first-line choice for estrogen replacement therapy (ERT) or HRT providing effective therapy with optimum adhesion, flux and tolerability profiles.

The effect of prolonged exercise on lipid peroxidation in eumenorrheic female runners.

Recently a protective role has been demonstrated for estrogens as free radical scavengers. In this study, lipid peroxidation was evaluated in eumenorrheic runners before and after participation in a half-marathon. Seven female runners who participated in regular training (average 25 miles x wk(-1) and reported regular menses (12/yr) served as subjects. Subjects were all in a low estrogen phase of their menstrual cycle as confirmed by menstrual record and plasma estradiol level (42.71 +/- 21.65 pg x mL(-1). Low density lipoprotein oxidation (formation of conjugated dienes) was determined 2 h prerace and 5 min after subject's completion of the race. Results showed a significant increase in lag phase time of conjugated dienes after prolonged exercise (28.43 +/- 4.89 min vs postrace 35.21 +/- 4.32 min, P < 0.05). No correlation between mean levels of estradiol and mean lipid peroxidation levels at rest, 5 min after exercise, or difference (prepost) was observed. Prolonged endurance exercise does not appear to increase potential for lipid peroxidation in trained eumenorrheic runners during a low estrogen phase of the menstrual cycle.

Dose-dependent inverse relationship between alcohol consumption and serum Lp(a) levels in black African males.

Serum or plasma levels of Lp(a) vary widely between individuals and are higher in Africans and their descendants compared with white persons. In whites, high serum levels of Lp(a) are associated with the premature development of atherosclerosis. In both ethnic groups, serum Lp(a) levels are highly genetically determined and only a few environmental or physiological factors, like testosterone or estrogen, have been shown to lower serum Lp(a) levels. In whites, alcohol consumption is associated with lower serum Lp(a) levels. However, the mechanism underlying this association and whether it holds true for blacks is not known. To address these questions, we analyzed serum Lp(a) levels in 333 middle-aged males of African descent from the Seychelles Islands (Indian Ocean). In addition, we analyzed the size of the apo(a) isoforms and the serum levels of albumin and sex hormones in a subset of 279 subjects. Serum Lp(a) levels were similar in teetotalers (median, 32.5 mg/dL; n=42) and occasional drinkers (median, 34.1 mg/dL; n=112). In contrast, individuals consuming 10 to 80 g of ethanol/d (n=83) and heavy drinkers (>80 g of ethanol/d, n=96) had a 9% and 32% lower median Lp(a) level than teetotalers, respectively (P=0.01). The size distribution of the apo(a) isoforms and the mean serum levels of albumin, estradiol, and luteinizing hormone were similar in teetotalers and occasional drinkers compared with moderate and heavy drinkers. These latter 2 groups had lower serum levels of testosterone and sex hormone-binding globulin. These data indicate that alcohol intake is associated in a dose-dependent manner with lower serum Lp(a) levels in males of African descent and that this association is not related to the size of the apo(a) isoforms, to the synthetic function of the liver, or to sex hormone biochemical status.

A pharmacokinetic study of injectable testosterone undecanoate in hypogonadal men.

Testosterone undecanoate (TU) provides testosterone (T) replacement for hypogonadal men when administered orally but requires multiple doses per day and produces widely variable serum T levels. We investigated the pharmacokinetics of a newly available TU preparation administered by intramuscular injection to hypogonadal men. Eight patients with Klinefelter's syndrome received either 500 mg or 1,000 mg of TU by intramuscular injection; 3 months later, the other dose was given to each man (except to one, who did not receive the 1,000-mg dose). Serum levels of reproductive hormones were measured at regular intervals before and after the injections. Mean serum T levels increased significantly at the end of the first week, from less than 10 nmol/L to 47.8+/-10.1 and 54.2+/-4.8 nmol/ L for the lower and higher doses, respectively. Thereafter, serum T levels decreased progressively and reached the lower-normal limit for adult men by day 50 to 60. Pharmacokinetic analysis showed a terminal elimination half-life of 18.3+/-2.3 and 23.7+/-2.7 days and showed a mean residence time of 21.7+/-1.1 and 23.0+/-0.8 days for the lower and higher doses, respectively. The area under the serum T concentration-time curve and the T-distribution value related to serum T concentration were significantly higher following the 1,000-mg dose than following the 500-mg dose. The 500-mg dose, when given as the second injection, yielded optimal pharmacokinetics (defined as mean peak T values not exceeding the normal range and persistence of normal levels for at least 7 weeks), suggesting that repeated injections of 500 mg at 6-8-week intervals may provide optimal T replacement. The mean serum levels of estradiol were normalized following the injections, and prolactin levels were normal throughout the study. Significant decrease of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels was observed, with the decrease in LH levels being more pronounced. There were no significant differences in serum LH and FSH levels between the two doses. Sex hormone-binding globulin (SHBG) levels before any T therapy were near the upper limit of normal for adult men and were reduced by approximately 50% just prior to the second dose of TU. The decreased SHBG levels produced by the first TU injection could have led to lower peak total T levels and to a more rapid clearance of T following the second TU injection. We conclude that single-dose injections of TU to hypogonadal men can maintain serum T concentration within the normal range for at least 7 weeks without immediately apparent side effects. It is likely that this form of T would require injections only at 6-8-week or longer intervals, not at the 2-week intervals necessary with currently used T esters (enanthate and cypionate). This injectable TU preparation may provide improved substitution therapy for male hypogonadism and, in addition, may be developed as an androgen component of male contraceptives.

THE EFFECT OF PROLONGED EXERCISE ON LIPID PEROXIDATION IN EUMENORRHEIC FEMALE ENDURANCE RUNNERS.

1834 Recently a protective role has been demonstrated for estrogens as free radical scavengers. In this study lipid peroxidation was evaluated in eumenorrheic runners before and after participation in a half-marathon. Nine female athletes who participated in regular training (average 25 miles/wk) and reported regular menses (12/yr) were recruited. Subject's mean BMI was 22.56±2.77,% fat 24.11±8.21, ht 65.5±2.48 cm. and weight 62.6±9.1 kg. Pre-race fasting bloodwork included determination of subject's mean level of estradiol, (63.22±44.87) total cholesterol(166.78±41.1) and HDL-C (61.33±13.03). LDL oxidation was determined by the formation of conjugated dienes at rest (fasting) and 5 min following completion of the race. Results showed a significant increase in lag phase time of conjugated dienes following prolonged exercise (baseline 27.06±5.05 min vs. post-race 34.56±3.96 min, p<.05). No correlation between mean levels of estradiol and mean lipid peroxidation levels at rest, 5 min following exercise, or difference (post-pre) was observed. It is concluded that prolonged endurance exercise does not increase potential for lipid peroxidation in trained eumenorrheic females who report normal menses.

ESTROGEN THERAPY AND EXERCISE INFLUENCE THE INCIDENCE OF SYMPTOMS ASSOCIATED WITH MENOPAUSE

1123 The purpose of this study was to investigate the possible influences of estrogen replacement and exercise on five common symptoms associated with menopause. Forty-five women between 3 and 10 years past menopause were recruited into one of four groups. Exercising women taking estrogen (XE) and exercisers not taking estrogen (XNE) engaged in endurance exercise at least 3 times per week for a minimum of one year. Sedentary women taking estrogen(NXE) and sedentary women not taking estrogen (NXNE) had not exercised regularly for at least a year. Subjects completed a questionnaire that assessed symptoms commonly associated with menopause. Mean estradiol levels(E2pg/ml) along with the percentage of women in each group experiencing hot flashes (HF), depression (DP), irritability (IRR), insomnia (INS), and loss of libido (LLIB) are listed in table.(table: estradiol means and frequency percentages, * = χ2 categorical significance p<.05, means with same superscript are not significantly different)It was concluded that estrogen replacement therapy and exercise have positive effects on common symptoms reported to accompany menopause.

Premature Luteinization: Could It Be An Early Manifestation of Low Ovarian Reserve?

Objective: To gain insight into the physiologic significance of premature luteinization and to evaluate whether it could be a manifestation of low ovarian reserve. Design: Retrospective evaluation. Setting: Reproductive medicine unit. Patient(s): Thirty-one consecutively seen women with normal ovulation and unexplained infertility. Intervention(s): Induction of superovulation with hMG coupled with synchronized IUI. A GnRH agonist was not used during the study. Main Outcome Measure(s): Premature luteinization was defined as a progesterone/estradiol ratio of >1 on the day of hCG administration. Patients were evaluated during their first cycles of hMG treatment and then were divided into those with (study group) and those without (control group) premature luteinization. The ovarian reserve parameters were compared between the two groups. Result(s): Nineteen of the 31 patients with unexplained infertility demonstrated premature luteinization. Patient characteristics were similar between the study and control groups. Mean (±SD) day 3 FSH levels were 8.2 ± 3.3 and 6.6 ± 1.7 mIU/mL in the study and control groups, respectively. Mean (±SD) day 3 estradiol levels were significantly higher in the study than in the control group (74 ± 49 pg/mL vs. 30 ± 17 pg/mL, respectively). Mean (±SD) estradiol levels on the day of hCG administration also differed significantly between the study and control groups (760 ± 539 pg/mL vs. 1,568 ± 675 pg/mL, respectively). Likewise, the number of follicles that were ≥15 mm on the day of hCG administration was significantly lower in the study than in the control group (2.9 ± 1.5 vs. 4.3 ± 1.3, respectively). The total dose of hMG and duration of administration were similar in the two groups. The clinical pregnancy rates after four cycles of treatment were 15.8% and 41.7% in the study and control groups, respectively. Conclusion(s): This preliminary work suggests that, in cycles that are not treated with a GnRH agonist, signs of premature luteinization in patients with unexplained infertility could be an early manifestation of low ovarian reserve. It appears that hMG treatment in this group of patients could uncover the pathogenesis of their infertility.

Sex steroids in cardiopulmonary bypass

BackgroundSex steroids have immunomodulatory effects. No data exist on alterations of sex steroids during cardiopulmonary bypass (CPB). Cardiac surgery with CPB releases an immunological response with complement and cytokine activation.ResultsPlasma estradiol and progesterone levels before and immediately after CPB were measured in 11 patients. During CPB, mean estradiol levels decreased from 29 to 15 pg/ml and progesterone levels rose from 0.13 to 0.90 ng/ml. These changes were statistically significant.ConclusionsThese are the first preliminary results evaluating plasma levels of sex steroids during CPB. Whether alterations in estradiol and progesterone levels influence complement and cytokine activation during bypass or vice versa is currently being investigated.

The pharmacodynamic effects of an oral contraceptive containing 3 mg micronized 17β-estradiol and 0.150 mg desogestrel for 21 days, followed by 0.030 mg desogestrel only for 7 days

During oral treatment with 3 mg micronized 17β-estradiol and 0.150 mg desogestrel for 21 days followed by 0.030 mg (A) desogestrel (15 women) or placebo (B) (14 women) for 7 days, ovarian function, bleeding pattern and estradiol levels were evaluated. The study was performed in a group-comparative, double-blind fashion. During a pre-treatment control cycle, using ultrasound scan, follicular diameter was measured on cycle days 10–16 and endometrial thickness on one of cycle days 22–26. Estradiol was measured at time of ultrasound scan and progesterone three times in the luteal phase. During three treatment cycles, follicular diameter and endometrial thickness were monitored three times weekly and at the same time, estradiol and progesterone were measured. Treatment resulted in anovulation in all women. Maximum and mean estradiol levels were approximately 900 pmol/l and 550 pmol/l during treatment, respectively, and approximately 200 pmol/l during the estradiol-free weeks in both groups. Ten women showed ovarian activity (follicle size ≥ 15 mm) during treatment, seven in group A and three in group B. Endometrial thickness decreased approximately 3 mm during treatment in both groups. The incidence of breakthrough bleeding and spotting was higher in group A when compared to group B. The study indicates that the combination of 3.0 mg micronized estradiol and 0.150 mg desogestrel is an effective and safe contraceptive, offering an acceptable cycle control. The addition of a low dose of desogestrel during the pill-free period did not further suppress ovarian activity nor improve the bleeding pattern. The results of this study should be interpreted with great care, since the number of women studied is relatively small.

A randomized, controlled trial of estradiol replacement therapy in women with hypergonadotropic amenorrhea.

Premature ovarian failure is classically defined as menopause occurring before age 40 and is associated with elevated serum FSH levels. If elevated FSH levels indicate lack of ovarian feedback and depletion of primordial follicles, women with prematurely elevated FSH levels should have infertility. However, there are many reports of pregnancies in affected women occurring during estrogen therapy leading to the hypothesis that estrogen may have a salutary effect on folliculogenesis and conception. This randomized, controlled trial was designed to investigate whether estrogen replacement therapy offered a significant therapeutic benefit in hypergonadotropic amenorrhea and to evaluate the potential pathophysiologic mechanisms that would explain the reported pregnancies. Thirty seven women, aged 16 to 40, with menstrual dysfunction and documented FSH levels elevated above the 95% confidence limits of the mid-cycle gonadotropin peak of the normal menstrual cycle (> 40 IU/L 2nd IRP hMG in our RIA) on at least two occasions, entered the study. The average duration of their amenorrhea was 15.9 months (range 2-96 months). Subjects were randomized to begin estradiol replacement (micronized estradiol [Estrace TM], 2 mg orally each day) or no therapy for 6 weeks in a 12-week, cross-over design with weekly monitoring by both pelvic ultrasonography and serum hormone levels. Thirty-one women completed the entire randomized study. As expected, estradiol therapy increased mean serum estradiol levels by 98 pg/mL and was associated with a significant decrease in mean LH and FSH levels (LH: 45.4 IU/L 2nd IRP hMG vs. 37.1 IU/L, FSH: 63.4 IU/L vs. 40.6 IU/L, geometric means). However, there was no effect of estradiol replacement on mean ovarian volume, the number or size of new follicles, or the ovulation rate in all subjects or in the subset with no identified cause for their hypergonadotropic hypogonadism (n = 20). Two pregnancies occurred during the randomized trial, one on and one off estradiol. In both arms of the study, the majority of subjects developed cystic ovarian structures by ultrasound that were temporally associated with increasing serum estradiol levels, indicating functional ovarian follicles. Seventy-eight percent of all subjects grew at least one new follicle over 10 mm in diameter and 46% ovulated at least once, as determined by a serum progesterone level more than 4 ng/mL. Although ovulations were significantly more common in the 10 women subjects who had less than 3 months of amenorrhea (all of whom ovulated) than in the 27 with greater than 3 months of amenorrhea (only 7 of whom ovulated (26%), P < 0.001), there was no significant difference in eventual pregnancies (2 of the 10 women with less than 3 months of amenorrhea vs. 3 of the 27 with greater than 3 months of amenorrhea, P = 0.47). We conclude that in hypergonadotropic women with amenorrhea: 1) folliculogenesis occurs often but is less frequently followed by ovulation and rarely by pregnancy, suggesting that elevated FSH is a marker of oocyte dysfunction occurring distinct from and earlier than granulosa cell or follicular dysfunction; and 2) estrogen therapy does not improve the rate of folliculogenesis or ovulation.

Endocrine function of the peri- and postmenopausal ovary

The concentration of sex steroids in peripheral and ovarian venous blood was measured in 130 perimenopausal women. We found that the postmenopausal ovary continues to secrete a large amount of testosterone and a moderate amount of androstenedione, estrone, and dehydroepiandrosterone. Although the mean estradiol levels in the ovarian vein of postmenopausal women was low, a few subjects showed estradiol levels higher than 50 pg/ml. Postmenopausal ovaries probably continue to secrete estradiol under some endocrine conditions. These data show that the postmenopausal ovary maintains some secretory function related to estrone and estradiol. However, the endocrine effect of the postmenopausal ovary may be related to its contribution of androgens to the plasma pool of estrogens through extragonadal conversion.