Normal Estradiol Levels Research Articles

Challenges and diagnosis in therapy of secondary amenorrhoea in caesarean section patient with postpartum haemorrhage B-lynch sutures: a case report

Introduction and importance: International Federation of Gynecology and Obstetrics (FIGO) and WHO report the incidence of postpartum haemorrhage (PPH) reaches 1–10% and contributes to an increase in postpartum maternal mortality with uterine atony as the most common cause. B-Lynch method is a suturing technique to overcome PPH. Although this method has proven useful as an emergency life-saving measure, the post-procedure complications are still able to occur. Presentation of case: The patient was not menstruating for 14 months after giving birth through caesarean section with B-Lynch due to PPH. Before pregnancy, she had regular menstruation cycle and normal menstrual duration. Her general and gynaecological status were normal. Ultrasound showed the impression of uterine hypoplasia and endometrium that were difficult to assess while both ovaries were normal. Diagnostic hysteroscopy showed a severe degree of Asherman’s syndrome. The results of FSH, LH and estradiol were normal. Discussion: B-lynch suture is performed as a method to stop PPH in uterine atony. Secondary amenorrhoea occurs as a complication of B-lynch. Compression action of B-lynch can cause progressive myometrium necrosis resulting in synechiae and blockade of uterine blood flow. This will interfere with the development of the uterus. Intrauterine adhesions and amenorrhoea with normal levels of FSH, LH, and estradiol support the diagnosis of Asherman’s syndrome. Conclusion: This case shows that the B-Lynch procedure, which is the worldwide recommended method for treating postpartum haemorrhage due to its high success rate, can cause complications of Asherman’s syndrome and cause secondary amenorrhoea.

Mosaic Form of Turner Syndrome

Objective: To report a case of breast growth disorder in a mosaic form of Turner Syndrome. Turner syndrome is a chromosomal condition characterized by small height and primary ovarian insufficiency that affects one in every 2500 female births. Mosaicism is likely to occur when monosomy X develops in only a few cells during development. The clinical presentation of Turner syndrome mosaicism is atypical, with symptom severity varying based on the number of affected cells. This case discusses issues with secondary sex development, including mild hyperandrogenism, and explores how combination hormonal treatment can aid in enhancing secondary sex development.
 Method: Case Report.
 Case: A 21-year-old woman presented with chief complaint of the lack of breast enlargement. She exhibited normal genitalia internally and externally and had a regular menstrual cycle. Karyotyping revealed a mosaic pattern of 45, X/46, XX (1 percent/99%) with normal estradiol levels and elevated testosterone levels (indicating mild hyperandrogenism). The patient underwent two cycles of hormone therapy using Ethinyl Estradiol and Drospirenone, resulting in breast growth progression from Tanner stage 1 to Tanner stage 2.
 Conclusion: Mosaicism in Turner syndrome is plausible, and the severity of clinical symptoms correlates with the number of defective chromosomes. The presentation of Turner syndrome mosaicism varies, and therapy should be tailored to address specific symptoms. While breast development is observed in some girls with Turner Syndrome, instances of breast growth disorder may occur, involving estrogen activity and estrogen receptor sensitivity. Although the exact cause of impaired breast growth remains unknown, administering estrogen in such cases can improve secondary sexual characteristics.
 Keywords: mild hyperandrogenism, mosaicism, turner syndrome

FRI228 Primary Adrenal T-cell Lymphoma: A Case Report

Abstract Disclosure: H. Tabassum: None. S. Xu: None. A. Manavalan: None. Introduction: Primary T-cell adrenal lymphoma (PAL) is exceedingly rare. Adrenal insufficiency (AI) is common in these cases. Here we describe a patient with bilateral, large, T-cell PAL with rapid progression, without adrenal insufficiency. Clinical Case: A 62-year-old male, with coronary artery disease and recent coronary intervention, hyperlipidemia and hypertension presented to the hospital with abdominal pain, fever, night sweats and weight loss for a month. Work up revealed a 5.8 cm left adrenal mass with 14% absolute washout, measuring 34 Hounsfield Units (HU) pre-contrast, 68 HU postcontrast, and 63 HU on delayed images, and a 5.2 cm right adrenal mass with 42% absolute washout, measuring 35 HU pre-contrast, 81 HU postcontrast, and 62 HU on the delayed images with no other suspicious lesions or lymphadenopathy. The patient demonstrated no clinical symptoms or signs of adrenal hormone excess or deficiency. Levels of renin, aldosterone, serum cortisol, ACTH, 24-hour urine free cortisol, serum metanephrines, and thyroid function were normal. Additional tests to rule out adrenal cortical carcinoma (ACC) revealed normal levels of androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and estradiol. Persistent non-significant elevation of 11-deoxycortisol was observed at 51 ng/dL and 63ng/dL (Ref < 42 ng/dL). Adrenal biopsy was suggested but deferred due to the increased risk of hemorrhage given recent coronary revascularization and use of dual antiplatelet therapy. Follow up imaging in a few weeks revealed diffuse, retroperitoneal lymphadenopathy with unchanged adrenal masses. A lymph node biopsy confirmed a diagnosis of peripheral T-cell lymphoma. The left adrenal gland demonstrated an uptake SUV of 22.7 and the right, 19.17 on FDG PET. The patient was initiated on chemotherapy with etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin. Imaging three months later revealed a marked decrease in FDG activity SUV 6.98 g/mL on the left and SUV up to 3.32 g/mL on the right. Adrenal function remained intact on follow up. Conclusion: Peripheral T-cell lymphoma with adrenal involvement is an extremely rare and aggressive disease with rapid progression. Mostly seen in males over the age of 50, it may present with abdominal pain, B symptoms or both. While ACC is usually unilateral, lymphoma and metastatic disease may present bilaterally, however, other imaging features can be similar. AI is expected when 90% of the adrenal glands are destroyed by tumor infiltration, however, this does not always correlate with tumor size. In our patient, AI was not observed on presentation or follow up. As adrenal insufficiency can occur at any time in the disease course and may mimic symptoms of cancer or chemotherapy, the clinician should always be vigilant for its development in these cases. Presentation: Friday, June 16, 2023

Linking Cardiovascular Risk With Estradiol Level in Men.

Aim To study the relationship between the cardiovascular risk and the level of estradiol in men of young and middle age. The main group included 71 patients with newly diagnosed hyperestrogenia (HE) (serum estradiol >41.2 pg/ ml). Using pseudorandomization, 68 men with normal estradiol level and age- and body weight index (BWI)-matched with the main group were included into the control group. Anthropometric data, bioimpedance variables, blood pressure (BP), and concentrations of estradiol, testosterone, glucose, and total cholesterol were analyzed in both groups.Results Patients of the main and control groups did not differ in age, BWI, and smoking status. Testosterone concentration was 10.18 nmol/l in the HE group and 12.18 nmol /l in the control group (p=0.006). Systolic BP was 142.0 mm Hg in the HE group and 135.2 mm Hg in the control group (p=0.011); diastolic BP was 90.3 mm Hg in the HE group and 86.2 mm Hg in the control group (p=0.008). Total cholesterol was 5.87 mmol/l in the HE group and 5.33 mmol/l in the control group (p=0.023). Blood glucose did not differ between the groups. The presence of HE in men 2.11 times (р=0.038) increased the probability of arterial hypertension. The intergroup difference by the SCORE scale did not reach statistical significance (р=0.172). BWI, waist and hip circumferences, and bioimpedance body composition parameters did not differ between the groups.Conclusion In the studied cohort of young and middle-aged men, HE was an independent predictor for the presence of arterial hypertension. There were no significant intergroup differences in the total risk of cardiovascular diseases calculated with the SCORE scale.

The relationship between serum estrogen concentration and post-dural puncture headache: a retrospective study.

Post-Dural puncture headache (PDPH) is a severe and undesirable complication for the patient and anesthesiologist. PDPH is more common in female patients. However, its relationship with plasma estrogen levels has not been demonstrated. This study aimed to investigate the relationship between estrogen levels and PDPH in patients who underwent spinal anesthesia for in vitro fertilization (IVF) with supraphysiological estrogen levels. In this retrospective study, the data of patients between the ages of 18-45 with the following characteristics were included in the study: those who underwent IVF procedure between January 2021 and August 2022, in the ASA I-II risk group, and who underwent spinal anesthesia using a 25 G Quinke-tipped spinal needle at the L3-L4 or L4-L5 vertebra levels. The 48 patients in the study were in two groups according to their estradiol values: 'Supra physiological estradiol levels' (Group I=24 patients) and 'Normal estradiol levels' (Group C=24 patients). The relationship between PDPH and estrogen, progesterone, spinal needle diameter, and patient demographic characteristics were evaluated. The estrogen and progesterone levels of patients in Group I were higher than in Group C (p<0.001 and p<0.001, respectively). PDPH was present in 6 (25%) patients in Group I and 5 (20.8%) patients in Group C (p=0.731). There was no significant correlation between PDPH and estrogen and progesterone levels (p>0.05). Since there is no relationship between the supraphysiological estrogen level and PDPH, high serum estrogen level should not be considered as an additional risk factor for PDPH in the decision of anesthesia type for IVF procedure.

Influence of Estradiol-Producing Ovarian Tumors on the Maturation Index of Cervical Cytology in Postmenopausal Women

Introduction: The aim of the study was to evaluate the influence of estradiol-producing ovarian tumors, including surface epithelial-stromal tumors, on the cervical cytology of postmenopausal women. Methods: This case-controlled study included 160 postmenopausal women who underwent a gynecological surgery between January 2009 and December 2016. The relationship between serum estradiol levels and the maturation index of cervical cytology was examined. Patients with ovarian tumors and a high estradiol level (≥28 pg/mL) constituted the estradiol-producing ovarian tumor group (30 women, including 23 with surface epithelial-stromal tumors). The maturation index of this group was compared with that of the control group (130 women with normal estradiol levels [<28 pg/mL] with either ovarian tumors or uterine tumors). Results: For all patients, the serum estradiol levels were significantly correlated with the maturation index (p < 0.001, r = 0.65). The maturation index of the estradiol-producing ovarian tumor group was significantly higher than that of the control group (0.67 ± 0.21 vs. 0.075 ± 0.16, p < 0.001). The area under the receiver operating characteristic curve for the maturation index was 0.94. The best maturation index cut-off level for estradiol-producing ovarian tumors was 0.20. Using this cut-off, the sensitivity and specificity were 94% and 82%, respectively. Conclusion: Estradiol-producing ovarian tumors influence cervical epithelial maturation in postmenopausal women. An increased maturation index may trigger the early detection of asymptomatic ovarian tumors.

Changes in anthropometric characteristics, androgen and estrogen levels during correction of male hypogonadism with testosterone or hCG: results of a retrospective comparative study

Background: The use of testosterone replacement therapy (TRT) is widespread. Despite the positive changes, such as: an increase in testosterone levels, an improvement in erectile function and an increase in libido, it is possible to develop a negative manifestation — hyperestrogenism. To date, there are no studies assessing the prevalence of hyperestrogenism in the presence of TRT.Aim: To study the reliability of an increase in total testosterone and estradiol levels and changes in total weight, body mass index (BMI), waist circumference (WC) and hips (OB), depending on the type of TRT and hCG therapy.Materials and methods: For retrospective analysis, the medical records of patients with baseline testosterone deficiency and normal estradiol levels, who were prescribed TRT or hCG therapy, were selected. The patients were divided into 3 groups depending on the form of TRT and hCG therapy. The level of testosterone, estradiol, sex hormone binding globulin (SHBG), weight, OT, OB, BMI in each group was assessed 2 times — before the appointment of treatment and at different periods of treatment, for example, after 3–6–9 and 12 months. Most of the patients had a period of monitoring these parameters before the appointment of TRT or hCG therapy and after 6 months.Results: The increase in the levels of total testosterone and estradiol against the background of TRT in the total sample was 109.6% and 111.3%, respectively. In each group, increases in total testosterone and estradiol levels were significant, p ≤ 0.001. The level of total testosterone to physiological values increased only in the 2-nd group — reaching the average-normal, recommended levels, from 8.7 ± 0.5 (2.5) to 16 ± 2 (10). The maximum rises in total testosterone, as well as estradiol, were noted in the 1st group, from 9.5 ± 0.72 nmol / L (3) to 24.9 ± 2.7 nmol / L (11.62)) and with 24.19 ± 2 (8.5) to 58.1 ± 4 (18.1), respectively. TRT, like hCG therapy, promotes an increase in the level of estradiol, which was demonstrated in all groups, and not only in group 1-st: in group 2-nd from 28.1 ± 2.3 (11.3) to 55 ± 4 (20) and in the 3-rd group from 27.1 ± 2.5 (10.5) to 55.8 ± 4.6 (19.6). On average for the entire sample, from 26.6 ± 1.32 (10.2) to 56.2 ± 2.5 (19). Weight loss on TRT was significant only in the 2-nd group, and in all parameters — weight, BMI, waist and hip circumference. In the 3-rd group, BMI, WC and OB values also slightly decreased. In the 1-st group, the total weight slightly increased, while the BMI did not change, as did the OB value, and the OT value decreased slightly.Conclusion: TRT significantly increases the levels of total testosterone and estradiol, contributing to the normalization of testosterone levels, as in the 2-nd group, or the development of supraphysiological levels of total testosterone and hyperestrogenism, as in the 1st and 3-rd groups. Given that there is a strong belief that TRT leads to significant weight loss, our study confirmed this statement only in the 2-nd group.

Изменения антропометрических характеристик, уровня андрогенов и эстрогенов при коррекции мужского гипогонадизма препаратами тестостерона или хорионического гонадотропина: результаты ретроспективного сравнительного исследования

Background: The use of testosterone replacement therapy (TRT) is widespread. Despite the positive changes, such as: an increase in testosterone levels, an improvement in erectile function and an increase in libido, it is possible to develop a negative manifestation — hyperestrogenism. To date, there are no studies assessing the prevalence of hyperestrogenism in the presence of TRT. Aim: To study the reliability of an increase in total testosterone and estradiol levels and changes in total weight, body mass index (BMI), waist circumference (WC) and hips (OB), depending on the type of TRT and hCG therapy. Materials and methods: For retrospective analysis, the medical records of patients with baseline testosterone deficiency and normal estradiol levels, who were prescribed TRT or hCG therapy, were selected. The patients were divided into 3 groups depending on the form of TRT and hCG therapy. The level of testosterone, estradiol, sex hormone binding globulin (SHBG), weight, OT, OB, BMI in each group was assessed 2 times — before the appointment of treatment and at different periods of treatment, for example, after 3–6–9 and 12 months. Most of the patients had a period of monitoring these parameters before the appointment of TRT or hCG therapy and after 6 months. Results: The increase in the levels of total testosterone and estradiol against the background of TRT in the total sample was 109.6% and 111.3%, respectively. In each group, increases in total testosterone and estradiol levels were significant, p ≤ 0.001. The level of total testosterone to physiological values increased only in the 2-nd group — reaching the average-normal, recommended levels, from 8.7 ± 0.5 (2.5) to 16 ± 2 (10). The maximum rises in total testosterone, as well as estradiol, were noted in the 1st group, from 9.5 ± 0.72 nmol / L (3) to 24.9 ± 2.7 nmol / L (11.62)) and with 24.19 ± 2 (8.5) to 58.1 ± 4 (18.1), respectively. TRT, like hCG therapy, promotes an increase in the level of estradiol, which was demonstrated in all groups, and not only in group 1-st: in group 2-nd from 28.1 ± 2.3 (11.3) to 55 ± 4 (20) and in the 3-rd group from 27.1 ± 2.5 (10.5) to 55.8 ± 4.6 (19.6). On average for the entire sample, from 26.6 ± 1.32 (10.2) to 56.2 ± 2.5 (19). Weight loss on TRT was significant only in the 2-nd group, and in all parameters — weight, BMI, waist and hip circumference. In the 3-rd group, BMI, WC and OB values also slightly decreased. In the 1-st group, the total weight slightly increased, while the BMI did not change, as did the OB value, and the OT value decreased slightly. Conclusion: TRT significantly increases the levels of total testosterone and estradiol, contributing to the normalization of testosterone levels, as in the 2-nd group, or the development of supraphysiological levels of total testosterone and hyperestrogenism, as in the 1st and 3-rd groups. Given that there is a strong belief that TRT leads to significant weight loss, our study confirmed this statement only in the 2-nd group.

Coronary artery calcification parameters in patients with coronary heart disease depending on the level of sex hormones

Abstract Funding Acknowledgements Type of funding sources: None. Introduction. In recent years, a lot of publications have been devoted to calcinosis of the coronary arteries as an important predictor of atherosclerosis. Particular attention is paid to gender-specific aspects of the pathogenesis and pathomorphology of Ischemic heart disease, as well as the levels of major sex hormones in both sexes. Goal. To study the severity of coronary heart disease in patients with Ischemic heart disease depending on the level of sex hormones, gender characteristics, and age. Methods. We studied 281 patients (147 women and 134 men) in the age range of 35-65 years with a previous (more than 30 days before inclusion in the study) acute myocardial infarction. The study program included determining the level of sex hormones (women - follicle-stimulating hormone, testosterone; men-testosterone, estradiol). Determination of the degree of coronary artery calcification was evaluated without contrast enhancement using ECG-synchronized MSCT. The volume and weight of total coronary calcium, Ca SCORE (according to the standardized quantitative system for measuring the calcium index-classifications Interpretation Guides, Mayo Clinic (1999) (low, moderate, moderately high, high) was used. Results. In the female groups (35-55 years old and 56-65 years old), all MSCT indicators of coronary artery calcification are lower than in male peers (p &amp;lt;0.01). For women, CA SCORE at 35-55 years old and 56-65 years old was 71.3 (25% and 75% percentiles, respectively: 22.2; 95.6) and 73.9 (45.1; 116.1), p = 0.247; in men - 144.1 (59.4; 184.8) and 189.1 (94.2; 226.1), p = 0.006. In women of both age groups, hyperandrogenism (testosterone &amp;gt; 3 nmol/l) was characterized by higher values of total coronary calcium (p &amp;lt; 0.001), total coronary calcium (p &amp;lt; 0.01) and coronary calcium index (p &amp;lt; 0.01). Independent direct associations of high testosterone with coronary calcification in women are confirmed by a series of covariance analyzes. Low testosterone in men (&amp;lt;12 nmol/l) was associated with an increase in MSCT indices of coronary artery calcification in the older age category (p &amp;lt; 0.001 for peers with normal androgen). Hyperestrogenia (estradiol ≥0.194 nmol/l) in men in both age groups was characterized by higher values of all indicators of coronary calcification in comparison with men with normal levels of estradiol (p &amp;lt;0.001-0.05), reaching maximum severity in men aged 56- 65 years old with high estradiol. According to the covariance analysis, the main hormone that directly determines Ca SCORE in men with coronary artery disease at the age of 35-65 years was the level of estradiol ≥0.194 nmol/l (p &amp;lt; 0.01). Conclusion. In the category of patients with myocardial infarction 35-65 years old, the coronary calcium index in women has lower values in comparison with men and does not significantly increase with age, directly depending on the level of total testosterone. In men, Ca Score is positively associated with concentration of estradiol ≥0.194 nmol/l.

An Adult With Hair Loss! a Rare Case of Non-Classical 3β Hydroxysteroid Dehydrogenase (3β HSD) Deficiency

Introduction: Congenital adrenal hyperplasia (CAH) is the most frequent cause of adrenal insufficiency and ambiguous genitalia in newborn. Unlike 21-hydroxylase and 11β- hydroxylase deficiencies, classical 3β hydroxysteroid dehydrogenase (3β HSD) deficiency affects steroid biosynthesis in both the adrenals and the gonads. We present a rare case of suspected 3β HSD in an adult with hair loss. Case: 33 years old with female with no PMH/prior pregnancies was referred to endocrinology for low testosterone, male pattern hair loss and decreased libido for 2 years. At onset of symptoms, she was following an intensive exercise regimen for weight loss and was using Oxandrolone for 2 months to promote muscle mass. She now reports increased axillary and pubic hair growth but loss of scalp hair as well as fatigue. Menarche was at 14 years. Menstrual cycles are regular but with hypomenorrhea. Physical examination showed normal BP, signs of male pattern hair loss on scalp. light terminal hair growth over abdomen, middle thighs and around areola but without galactorrhea. Labs remarkable for normal sodium and potassium, A1c 5.2%, ACTH of 7.2, Cortisol of 8.2 (5–25 µg/dl), TSH of 1.43 (0.5–5.0 mIU/L), Free T4 of 1.28 (0.8–1.8 ng/dl), Estrone 102 (17–200 pg/ml), Normal DHEA 133, Total testosterone <3 (8–60 ng/dl), Free testosterone 0.4 (0.3–1.9 ng/dL), LH 7 (1.0–18.0 mIU/mL), FSH 9.6 (2.0–12.0 mIU/mL), Estradiol 45.9 (15–350 pg/mL),low 17-hydroxyprogesterone of 11 (<80 ng/dL), DHEA-S of 88 (31–228 µg/dL), low Androstenedione of 28 (80–240 ng/dL) and Dihydrotestosterone 6.3 (normal). MRI brain revealed a normal pituitary gland, slightly enlarged for age. Co-syntropin stimulation test has been delayed due to the pandemic. Discussion: 3β HSD converts delta-5 steroids (pregnenolone, 17-hydroxypregnenolone, DHEA, androstenediol) to delta-4 steroids (progesterone, 17-hydroxyprogesterone, androstenedione, testosterone) respectively. Delta-4 steroids were low in our patient. Increased ratio of delta 5 steroids: delta 4 is characteristic of 3β HSD. Most cases of 3β HSD deficiency present as neonates with hyponatremia, hyperkalemia, and ambiguous genitalia but a non-salt wasting form has occasionally been described in older patients. The non-classical form often manifests as menstrual irregularities and hirsutism along with possible male pattern hair loss of varying degrees in women. The normal levels of estradiol and estrone are likely due to peripheral conversion of androstenedione by aromatase. 3β HSD deficiency is usually treated with steroids which helps resolve most symptoms.

Systemic estradiol levels with low-dose vaginal estrogens.

Objectives:To critically evaluate published systemic estradiol levels during use of low-dose vaginal estrogens considering detection method and estrogen dose; describe challenges with accurately measuring estradiol; and determine the normal estradiol level range in postmenopausal women.Methods:PubMed was searched for studies reporting systemic estradiol levels with lower-dose vaginal estrogens (≤25 μg estradiol or 0.3 mg conjugated equine estrogens). Estradiol levels at baseline and during treatment, area under the curve, and maximum estradiol concentrations were summarized by dose within assay type. A proposed range of systemic estradiol in normal, untreated, postmenopausal women was estimated by conservatively pooling means and standard deviations from published studies.Results:Mean basal estradiol levels were 3.1 to 4.9 pg/mL using liquid or gas chromatography/mass spectroscopy (LC or GC/MS/MS) with a range of undetectable to 10.5 pg/mL using radioimmunoassay. Systemic estradiol levels with vaginal estrogens reflected their doses as measured with LC or GC/MS/MS in different studies: 7.1 to 9.1 pg/mL and 16.7 to 22.7 pg/mL with a 25-μg softgel capsule insert and a tablet insert, respectively; 4.6 to 7.4 pg/mL and 6.6 to 14.8 pg/mL with a 10-μg softgel capsule and a tablet insert, respectively; and 3.6 to 3.9 pg/mL with a 4-μg softgel capsule insert. A mean systemic estradiol concentration ranging from undetectable to 10.7 pg/mL is proposed as an estimate for basal estradiol levels in normal, untreated, postmenopausal women. Systemic estradiol absorption may be influenced by the placement of estradiol higher (as with an applicator) versus lower (as without an applicator) in the vagina, as estradiol transport to the uterus would be more likely further away than closer to the introitus.Conclusion:Serum estradiol concentrations were generally lower when measured with more specific and sensitive assays. Estradiol absorption was dose-dependent, and may be influenced by dose, formulation, and positioning in the vagina. Very low systemic estradiol absorption with low/ultralow-dose vaginal estrogens may potentially decrease any adverse events that may be associated with higher doses of vaginal estrogens used for treating moderate to severe VVA due to less estradiol exposure.

Uterine aquaporin expression is dynamically regulated by estradiol and progesterone and ovarian stimulation disrupts embryo implantation without affecting luminal closure.

The study investigated the effect of normal and supraphysiological (resulting from gonadotropin-dependent ovarian stimulation) levels of estradiol (E2) and progesterone (P4) on mouse uterine aquaporin gene/protein (Aqp/AQP) expression on Day 1 (D1) and D4 of pregnancy. The study also examined the effect of ovarian stimulation on uterine luminal closure and uterine receptivity on D4 of pregnancy and embryo implantation on D5 and D7 of pregnancy. These analyses revealed that the expression of Aqp3, Aqp4, Aqp5 and Aqp8 is induced by E2 while the expression of Aqp1 and Aqp11 is induced by P4. Additionally, P4 inhibits E2 induction of Aqp3 and Aqp4 expression while E2 inhibits Aqp1 and Aqp11 expression. Aqp9, however, is constitutively expressed. Ovarian stimulation disrupts Aqp3, Aqp5 and Aqp8 expression on D4 and AQP1, AQP3 and AQP5 spatial expression on both D1 and D4, strikingly so in the myometrium. Interestingly, while ovarian stimulation has no overt effect on luminal closure and uterine receptivity, it reduces implantation events, likely through a disruption in myometrial activity and embryo development. The wider implication of this study is that ovarian stimulation, which results in supraphysiological levels of E2 and P4 and changes (depending on the degree of stimulation) in the E2:P4 ratio, triggers abnormal expression of uterine AQP during pregnancy, and this is associated with implantation failure. These findings lead us to recognize that abnormal expression would also occur under any pathological state (such as endometriosis) that is associated with changes in the normal E2:P4 ratio. Thus, infertility among these patients might in part be linked to abnormal uterine AQP expression.

The role of gonadal hormones in the hypoglossal discharge activity of rats exposed to chronic intermittent hypoxia

ObjectiveThe role of gonadal hormones in chronic intermittent hypoxia (CIH)-evoked hypoglossal nerve (XII) neuroplasticity has not been thoroughly studied. The purpose of this study was to reveal the effects of gonadal hormone concentration variations on the XII discharge activity of rats exposed to CIH and the corresponding relationship with 5-hydroxytryptamine (5-HT). MethodsThis study employed five groups of female rats and six groups of male rats. Gonadal hormone levels were modified through gonadal resection and daily supplementation with gonadal hormones in rats of both sexes. Rats in the CIH groups were exposed to an additional 4 weeks of CIH once the operative incision for gonadectomy had healed. Finally, XII spontaneous discharge activities were recorded, and serum estradiol, testosterone and 5-HT concentrations were detected by ELISA. ResultsAmong the female rats, the normal estradiol level groups expressed XII neuroplasticity, while the low estradiol level group failed to express this phenomenon. XII neuroplasticity was related to the serum estradiol concentration. In the male rats, XII neuroplasticity was successfully evoked in the normal testosterone level group but was suppressed in the low testosterone level group and aromatase inhibitor group. XII neuroplasticity was not significantly related to serum testosterone concentrations. Both estradiol and testosterone concentrations were related to 5-HT concentrations. ConclusionsThis is the first study to analyze the effects of gonadal hormones on XII neuroplasticity in both female and male rats. The results suggest that the estradiol level is related to XII neuroplasticity rather than the testosterone level, and testosterone may indirectly adjust XII neuroplasticity by converting to estradiol. Estradiol and testosterone levels are related to 5-HT levels in the respective genders.

THE RELATIONSHIP BETWEEN LEVELS OF ALDOSTERONE, ESTRADIOL AND SERUM MARKERS OF ENDOTHELIAL DYSFUNCTION IN HYPERTENSIVE WOMEN

Objective: To study the relationship between plasma levels of aldosterone, estradiol and serum markers of endothelial dysfunction (ED) such as stable nitric oxide metabolites NO2-+NO3- (NOx), endothelin-1 (ET-1), homocysteine (HC), von Willebrand factor (vWF) in nondiabetic women with essential hypertension (EH). Design and method: We examined 79 hypertensive, nondiabetic women (mean age 51,4 ± 6,5y, mean EH duration 8,5 ± 7,6y). 28% of the group were smokers, 54% were obese, 76% - with dyslipidemia. Regular menstrual function had 30% of the women, the rest of the group – postmenopausal (median duration of postmenopause was 5,7 ± 3,5y). Circulating NOx levels were studied by spectrophotometry, ET-1, HC, vWF levels – by immunoenzyme assay, aldosterone and estrogen levels - by immunoenzyme assay. Statistical analysis was done using the Statistica 10.0 software. Results: We compared the levels of ED markers in women with a normal (56%), and elevated levels of aldosterone (44%), as well as in women with a normal (62%) and low levels of estradiol (38%). Women with hiperaldosteronemia had higher concentration of NOx (45.3 ± 17.6 and 38.8 ± 16.5 mmol/l, respectively, p < 0.05), E-1 (1.4 ± 1.1 and 0.9 ± 0.8 fmol/l, respectively, p < 0.05) and vWF (1.6 ± 0.8 and 1.3 ± 0.9 mg/dl, respectively, p < 0.05). Aldosterone levels correlated with NOx (r = 0.36, p < 0.05), E-1 (r = 0.3, p < 0.05) and vWF (r = 0.34, p < 0.05) levels. Women with hypoestrogenemia had higher NOx (46.3 ± 16.9 and 37.5 ± 16.0 mmol/l, respectively, p < 0.05), E-1 (1.5 ± 1.1 and 0.8 ± 0.4 fmol/l, respectively, p < 0.05) and vWF (1.6 ± 0.9 and 1.2 ± 0.7 mg/dl, respectively, p < 0.05) levels as well. Estradiol levels correlated with NOx (r = -0.6, p < 0.05) and vWF (r = -0.5, p < 0.05) levels. Conclusions: Our results suggest that women in perimemopausal period demonstrate hormonal disorders with elevation of aldosterone level and decline of estrogen level, which are related to the increase of a number of substances considered as the markers of endothelial dysfunction.

Estrogen Levels Do Not Rise With Testosterone Treatment For Transgender Men

Existing transgender treatment guidelines suggest that for transmasculine treatment, there is a possible need for estrogen-lowering strategies adjunct to testosterone therapy. Further, guidelines advocate consideration of prophylactic female reproductive tissue surgeries for transgender men to avoid the possibility of estrogen-related health risks. Despite the paucity of objective data, some transgender men seek conversion inhibitors. We sought to determine estradiol levels in transgender men treated with testosterone therapy and the change in those levels with treatment, if any. Estradiol levels were extracted from the electronic medical records of 34 anonymized transgender men treated with testosterone therapy at the Endocrinology Clinic at Boston Medical Center. Data were sufficient to observe 6 years of follow-up. With increased testosterone levels in trans-gender men, a significant decrease in estradiol levels was noted. There was a significant negative correlation between testosterone levels and body mass index, which may serve to explain part of the mechanism for the fall in estradiol levels. Even though the fall in estradiol levels was significant statistically, the actual levels remained within the normal male range, even with 6 years of follow-up. These data suggest that when exogenous testosterone is used to achieve normal serum male testosterone levels for transgender men, it is converted to normal male levels of estradiol, with some decline in those estradiol levels that might be attributable to a fall in fat mass. There appears to be no role for aromatase conversion inhibitors or other estrogen-reducing strategies in trans-gender men. Abbreviation: BMI = body mass index.

Luteinizing hormone elevation in ovarian granulosa cell tumor: a case report and review of the literature

BackgroundOvarian granulosa cell tumors (GCTs) are the most common type of potentially malignant ovarian sex cord-stromal tumor. GCTs often produce estrogen and/or progesterone; consequently, symptoms related to hyperestrogenism are common at diagnosis. Nonspecific symptoms or signs associated with this neoplasm include amenorrhea and changes in various sex hormone levels, which can be hard to diagnose or explain. The aims of this report were to describe a case of GCT with rare presentations and to review the pertinent literature.Case presentationA 33-year-old woman presented with secondary amenorrhea and elevated LH with normal FSH and low estradiol levels. Laparoscopy revealed an ovarian GCT, and the patient underwent left adnexectomy and platinum-based chemotherapy. Removal of the ovarian GCT resulted in the normalization of LH levels and a return to spontaneous menses.ConclusionsThe mechanisms responsible for elevations in serum LH due to GCTs require further investigation. However, addressing the patient’s clinical problems remains the most important treatment consideration.

Loss of PI3K p110α in the Adipose Tissue Results in Infertility and Delayed Puberty Onset in Male Mice.

Deletion of PI3K catalytic subunit p110α in adipose tissue (aP2-Cre/p110αflx/flx, α−/− hereafter) results in increased adiposity, glucose intolerance, and liver steatosis. Because this endocrine organ releases hormones like leptin, which are important in reproductive physiology, we investigated the reproductive phenotype of α−/− males. Compared to controls, α−/− males displayed delayed onset of puberty accompanied by a reduction in plasma LH levels and testicular weight. At postnatal day 30, α−/− mice exhibited normal body weight but elevated fasted plasma leptin levels. Testicular leptin gene expression was increased, whereas expression of the cholesterol transporter StAR and of P450 cholesterol side chain cleavage enzyme was decreased. Adult α−/− males were infertile and exhibited hyperandrogenemia with normal basal LH, FSH, and estradiol levels. However, neither sperm counts nor sperm motility was different between genotypes. The mRNA levels of leptin and of 17-beta-dehydrogenase 3, and enzyme important for testosterone production, were significantly higher in the testis of adult α−/− males. The mRNA levels of ERα, an important regulator of intratesticular steroidogenesis, were lower in the testis of adult and peripubertal α−/− males. We propose that chronic hyperleptinemia contributes to the negative impact that disrupting PI3K signaling in adipocytes has on puberty onset, steroidogenesis, and fertility in males.

Роль гиперпролактинемии в генезе преждевременного телархе и ее коррекция у девочек первых пяти лет жизни

The family resource center MI «Dnipropetrovsk regional perinatal center with a hospital» DRC Isolated telarhe in girls of 1–5 years, often caused by increased levels of prolactin (PL), which plays an important role in the development of the female reproductive function (in general), and in mammohenezis (in particular). The aim of the study: to study the effectiveness of a drug Cyclodynon® on girls with an incomplete form of precocious puberty by the isosexual type – isolated telarhe on the base of increased levels of PL. Materials and methods. In the regional center of family planning on the basis of SI «Dnipropetrovsk regional perinatal center with a hospital» DRH survey was conducted in 30 girls aged from 1 to 5 years with premature isolated telarhe (PIT). Girls with isolated telarhe and a high level of PL were prescribed the drug, Cyclodynon® depending on the age and level of PL in serum at a dose from 1/8 of pill to 1 tablet (from 5 drops to 40 drops) in the morning on an empty stomach 1 time per day (guidelines of the Institute of health protection of children and adolescents of NAMS of Ukraine). Results. In the study to include 30 girls with isolated telarhe noted a steady increase of PL (up to 680 mIU/l for normal values 110-560 mIU/l) at relatively normal levels of gonadotropins and estradiol. Use of the drug of special extract of Vitex Agnus Castus – Cyclodynon® led to a gradual, within 3 months, reduce of prolactin levels to the normal range of 680 to 396 mIU/L. Reducing of prolactin levels correlated with regression of clinical signs of telarhe. No side effects or undesirable Cyclodynon® application within 3 months is not noted. Conclusion. A standardized herbal medicinal product Cyclodynon® with dopaminergic effect contributing to the normalization of PL for the treatment of girls with incomplete form of precocious puberty in isosexual type – isolated telarhe on the base of increased level of PL, is an effective and pathogenetically justified. This is confirmed by the results of clinical and hormonal reaserches. Key words: isolated telarhe, prolactin, Cyclodynon®.

A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice.

Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition.

PP.24.04

Objective: To study the relationship between changes in the content of estradiol and follicle-stimulating hormone (FSH), the restructuring process of the cardiovascular system in women with hypertension. Design and method: 64 women in the late reproductive age with hypertension not taking antihypertensive therapy. All determined by the level of estradiol and FSH. Depending on the degree of estradiol and FSH patients with hypertension were divided into groups. In group 1 (gr.) Included 34 hypertensive age 39,11 ± 4,3 years with the menstrual cycle and estrogen deficiency. In the 2nd c. - 30 with hypertension, age 39,14 ± 2,23 years, with the menstrual cycle and normal levels of estradiol and FSH. A comparison group of 20 healthy women, 38,45 ± 4,12 years with normal levels of estradiol and FSH without hypertension. Performed duplex scanning of the common carotid artery (CCA). Results: Observed expansion of the mean diameter of CCA in patients with hypertension and estrogen deficiency. Blood flow velocity in the CCA significantly lower in comparison with the control in patients with hypertension and gipoestrogeniya. Resistance index was higher in patients with hypertension 1 gr. in comparison with the control and patient 2 gr. The elastic properties of the wall of the carotid artery decreased: from 41,3 ± 10,8 x ∼ 3 / kPa in patients with hypertension and normal levels of estradiol to 36,4 ± 10,8 x Yu- 3 / kPa p = 0.034 for patients with hypertension with decreased levels of estradiol. The index of stiffness was higher in comparison with the control as in patients with hypertension estrogenodefitsitom, and without it. Conclusions: Duplex scanning of carotid arteries in women with hypertension shows expansion of the lumen of the CCA, reducing blood flow velocity, expressed against the backdrop of estrogen deficiency, indicating that the more significant changes in the vascular wall in hypertensive patients compared with having normal levels of estradiol.