Analysis of Natural and Synthetic Estrogens at Sub-PPT Levels In
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Alpha-Fetoprotein: the Major High-Affinity Estrogen Binder in Rat
Proc. Natl. Acad. Sci. USA Vol. 73, No. 5, pp. 1452-1456, May 1976 Biochemistry Alpha-fetoprotein: The major high-affinity estrogen binder in rat uterine cytosols (rat alpha-fetoprotein/estrogen receptors) JOSE URIEL, DANIELLE BOUILLON, CLAUDE AUSSEL, AND MICHELLE DUPIERS Institut de Recherches Scientifiques sur le Cancer, Boite Postale No. 8, 94800 Villejuif, France Communicated by Frangois Jacob, February 3, 1976 ABSTRACT Evidence is presented that alpha-fetoprotein nates in hypotonic solutions, whereas in salt concentrations (AFP), a serum globulin, accounts mainly, if not entirely, for above 0.2 M the 4S complex is by far the major binding enti- the high estrogen-binding properties of uterine cytosols from immature rats. By the use of specific immunoadsorbents to ty. AFP and by competitive assays with unlabeled steroids and The relatively high levels of serum AFP in immature rats pure AFP, it has been demonstrated that in hypotonic cyto- prompted us to explore the contribution of AFP to the estro- sols AFP is present partly as free protein with a sedimenta- gen-binding capacity of uterine homogenates. The results tion coefficient of about 4-5 S and partly in association with obtained with specific anti-AFP immunoadsorbents (12, 13) some intracellular constituent(s) to form an 8S estrogen-bind- provided evidence that at low salt concentrations,'AFP ac-' ing entity. The AFP - 8S transformation results in a loss of antigenic reactivity to antibodies against AFP and a signifi- counts for most of the estrogen-binding capacity associated cant change in binding specificity. This change in binding with the 4-5S macromolecular complex. -
Estrone-Compound-Pal-011921
ESTRONE COMPOUND What is this medicine? Estrone (es-trohn) E1 Estrone is a hormone derived from yams and may be given to women who no longer produce a sufficient amount on their own. It may be used to reduce menopause symptoms (e.g., hot flashes, vaginal dryness). It may be used to help prevent bone loss. It may also be used for other conditions as determined by your doctor. Compounded Drug Forms: BLA tablet, sublingual tablet, fast-burst sublingual tablet, vaginal tablet, troche, vaginal suppository, cream, gel What should I tell my health care provider before I take this medicine? Allergy to estrone Pregnant or breastfeeding Have undiagnosed severe vaginal bleeding Active cancer of the breast or uterus A history of blood clots, stroke or heart attacks Smoking while using this medication may increase your risk of blood clots. Have liver dysfunction or disease How should I use this medicine? Follow the package directions provided by Belmar Pharmacy and by your prescriber. Your dosage is based on your medical condition and response to therapy. Follow the dosing schedule provided carefully. Oral tablets may be taken with or without food, if it upsets your stomach take it with a small meal. Sublingual tablets and fast-burst sublingual tablets should be placed under the tongue or between the cheek and gums and held in place until fully dissolved. Avoid swallowing saliva to ensure best absorption into the blood stream. Avoid eating or drinking 15 minutes before or after taking sublingual tablet. Topical products can be applied to the inner arm, upper thigh, back of the knee, tops of the feet and inner wrists. -
VI.2 Elements for a Public Summary
VI.2 Elements for a Public Summary VI.2.1 Overview of disease epidemiology In women in menopausal period, the decrease of hormones (estrogen levels) result in genital areas becoming dry, itchy and more easily irritated. Vaginal atrophy is a frequent complaint of these women. Symptoms associated with vulvovaginal atrophy (VVA), such as lack of lubrication and pain with intercourse, affect 20% to 45% of midlife and older women. About 50% of otherwise healthy women over 60 years of age experience symptoms related to urogenital atrophy such as vaginal dryness, dyspareunia, burning, itching, as well as urinary complaints or infections of the lower urinary tract. As these alterations frequently affect the quality of life of postmenopausal women, it is important for doctors to detect their presence and offer treatment options. VI.2.2 Summary of treatment benefits Estriol normalizes the vaginal, cervical and urethral epithelium and thus helps to restore the normal microflora and the physiological pH in the vagina. Moreover, estriol increases the resistance of the vaginal epithelial cells to infection and inflammation and decreases the incidence of urogenital complaints. Estriol, which is an estrogen, can be used in the treatment of vaginal symptoms and complaints (vaginal dryness, itching, discomfort and painful intercourse) due to estrogen deficiency related to menopause (whether naturally or surgically induced). In a randomized clinical trial versus placebo, intravaginal application of a low dose of estriol (50 micrograms per application) the main endpoint was to evaluate the efficacy of the product by evaluation of the change in the maturation value of the vaginal epithelium after 12 weeks of treatment. -
Estrogen ------Active Ingredient Protective Neurosteroid I.E
Estrogen --------------------------------------------------------------- Active Ingredient protective neurosteroid i.e. neuromodulators, neuroprotective and regulate neurotransmission. • Estrogen (Estrone, Estradiol, Estriol) Before you take estrogen What is in this leaflet When you must NOT take it: This leaflet contains some information about your • If you are allergic to the active ingredient medication. It does not take the place of talking to • If the medication is expired or has not been stored your doctor or pharmacist. All medicines have risks correctly and benefits. Your doctor has weighed the risks of you • If you have or have history of breast cancer or taking this medication against the positive benefits other estrogen-dependent tumour they expect it will have for you. If you have any • If you have a history of venous thromboembolism concerns about taking this medicine, please contact (blood clots in the vein) us again or speak with your doctor or pharmacist for more information. Keep this leaflet with the medicine Let us know if you are: as you may need to read it again in the future. • Pregnant, planning on becoming pregnant, or breastfeeding What it is used for • Suffer from any other medical conditions such as migraine, diabetes, epilepsy This medication contains one or more active • or take any other medications ingredients of estrogens (estrone, estradiol, estriol). Estrogens play important roles in stimulating growth For a full list of precautions, please contact our of the reproductive tissues, maintaining healthy pharmacy bones, increasing the levels of neurotransmitters in the brain, and helping keep the cardiovascular system How to take estrogen healthy. Estrogens relieve symptoms (e.g. -
Feminizing Gender-Affirming Hormone Care the Michigan Medicine Approach
Feminizing Gender-Affirming Hormone Care The Michigan Medicine Approach Our goal is to partner with you to provide the medical care you need in affirming your gender. Our focus is on your lifelong health, safety, and individual medical and transition-related needs. The Michigan Medicine approach is based on the limited but growing medical evidence surrounding gender-affirming hormone care. Based on the available science, we believe mimicking normal physiology will provide you with the best balance of physical and emotional changes and long-term health. This philosophy aligns with current national and international medical guidelines in the care of gender diverse people. We are committed to staying up-to-date with the latest research and medical evidence to ensure you are getting the highest quality care. We know that there are competing approaches to gender-affirming care that are not based on validated scientific evidence. These approaches make scientifically unsubstantiated claims and have unknown short and long-term risks. We are happy to discuss these with you. Below are some answers to questions our patients have asked us about gender- affirming hormone care. We hope the Q&A will help you understand the medical evidence behind our approach to your gender-affirming hormone care, and how it may differ from other approaches, including the approach other well-known clinics in Southeast Michigan. Is there a benefit for monitoring both estrone (E1) and estradiol (E2) levels and aiming for a particular ratio? There are 3 naturally occurring human estrogens: estrone (E1), estradiol (E2), and estriol (E3). Your body naturally balances your estradiol and estrone ratio. -
Estriol Face Cream Handout
is used, most of the time it refers to Estradiol Hormone Health (E2), which is the highest concentration --80%-- during a woman's reproductive years (from & Skin Health puberty to pre-menopause). Estriol (E3) makes Dr. Randolph’s NEW up another 10% and Estrone (E1) makes up the last 10%. Estriol Face Cream Estriol (E3) is considered a "weak" estrogen which can be derived from plant sources. It does What is it? not need to be counterbalanced by progesterone, and does not have a systemic (widespread) effect Dr. Randolph's NEW prescription-only Estriol on the body. This makes estriol an ideal estrogen Face Cream consists of Estriol 0.3% , DMAE for topical use, since research suggests its 3%, and Hyaluronic Acid 0.5% mixed in a cream application remains in the skin, rather than in base. Dr. Randolph, along with Compounding the bloodstream. There is also evidence that Pharmacist Will McGalliard, developed this estriol, (sometimes called the "good estrogen") combination of ingredients to provide a may inhibit some of the unwanted effects of clinically-proven treatment that will boost estradiol by "binding" to estrogen receptors that collagen, reduce wrinkles, improve skin moisture typically promote cell proliferation. and elasticity. Who is it for? How does it work? For women or men who wish to improve the One of the many roles of estrogen in the body is appearance and health of their skin by boosting to increase the synthesis of collagen, which is the the development of underlying collagen skin's underlying support structure. Collagen structure, increasing elasticity and skin moisture, also promotes skin thickness and elasticity. -
Tibolone : a Selective Tissue Estrogenic Activity Regulator
JK SCIENCE DRUG REVIEW Tibolone : A Selective Tissue Estrogenic Activity Regulator Sudhaa Sharma, Annil Mahajan*, Sudesh Kumar*, Vishal R. Tandon** Tibolone is a STEAR (Selective tissue estrogenic postmenopausal women reporting female sexual activity regulator) (1). It is a synthetic steroid with tissue dysfunction (FSD) is significantly increased under selectivity that has progestogenic, some androgenic as tibolone in comparison with Estrogen progestron therapy well as estrogenic effects. It has been used as an with a better improvement of sexual function (7). In the alternative to estrogen replacement therapy in several first trial by Nevinny-Stickel (8), there was no significant European countries for almost 2 decades, primarily for improvement in regard to libido in women taking the prevention of postmenopausal osteoporosis and tibolone. On the contrary, the recent double blind and treatment of climacteric symptoms. placebo-controlled trial by Laan (9) has shown that Mechanism of action (2) : Tibolone itself has no treatment with tibolone significantly improved the biological activity; its effects are the results of the activity physiological aspects of sexual function in of its metabolites on various tissues. After administration, postmenopausal women, such as vaginal blood flow, tibolone is quickly metabolized into 3a-hydroxytibolone vaginal lubrication, and subjective measures, such as (3 ß OH-tibolone) and 3 ß-OH-tibolone compounds, sexual desire and arousability, but there was no difference which are also present in an inactive, sulfated form. A in the frequency of sexual intercourse, nonpenetrative third compound, the ?4- isomer, is formed from tibolone sexual activity, or initiation and rejection of sexual directly or from the 3 ß -OH-metabolites. -
Drugs for the Treatment of Menopausal Symptoms
Review Drugs for the treatment of menopausal symptoms † Susan R Davis & Fiona Jane Monash University, Alfred Hospital, Central Clinical School, Women’s Health Program, 1. Introduction Commercial Road, Prahran, Victoria, Australia 2. Which menopausal symptoms Importance of the field: Over the last decade, the management of the meno- merit treatment? pause has attracted extensive public and professional debate and has become 3. Pharmacotherapy for one of the most controversial areas in clinical practice. menopausal symptoms Areas covered in this review: This review provides an overview of the field, 4. New frontiers primarily from a clinical practice perspective. However, as we have incorpo- 5. Expert opinion rated in this ‘big-picture’ snapshot of the field both conventional and comple- mentary approaches to managing the menopause, it is not an exhaustive review of the literature. What the reader will gain: By reviewing menopausal management from the perspective of practicing clinicians, we hope readers will gain insight into decision making processes appropriate for dealing with symptomatic women. Take home message: Although most women do not require pharmacother- apy for menopausal symptoms, many are severely affected by estrogen defi- ciency at and beyond menopause and, for such women, hormone therapy is important if they are to retain an acceptable quality of life. This article consid- ers the drug treatment of the symptomatic postmenopausal woman and the safety issues related to these medications. Keywords: estrogen, HRT, menopause, progestogen Expert Opin. Pharmacother. (2010) 11(8):1329-1341 For personal use only. 1. Introduction Menopause is not only associated with symptoms that range from bothersome through to extremely distressing, it is also accompanied by hormonal changes that impact adversely on several non-reproductive systems. -
Label Extension of HERS, HERS II
Depo®-Estradiol Estradiol cypionate injection, USP WARNINGS: ESTROGENS INCREASE THE RISK OF ENDOMETRIAL CANCER. Close clinical surveillance of all women taking estrogens is important. Adequate diagnostic measures including endometrial sampling when indicated, should be undertaken to rule out malignancy in all cases of undiagnosed persistent or recurring abnormal vaginal bleeding. There is currently no evidence that the use of “natural” estrogens result in a different endometrial risk profile than “synthetic” estrogens at equivalent estrogen doses. (See WARNINGS, malignant neoplasms, Endometrial cancer.) CARDIOVASCULAR AND OTHER RISKS Estrogens with and without progestins should not be used for the prevention of cardiovascular disease. (See WARNINGS, Cardiovascular disorders.) The Women’s Health Initiative (WHI) study reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women (50 to 79 years of age) during 5 years of treatment with oral conjugated estrogens (CE 0.625 mg) combined with medroxyprogesterone acetate (MPA 2.5 mg) relative to placebo. (see CLINICAL PHARMACOLOGY, Clinical Studies.) The Women’s Health Initiative Memory Study (WHIMS), a substudy of WHI, reported increased risk of developing probable dementia in postmenopausal women 65 years of age or older during 4 years of treatment with oral conjugated estrogens plus medroxyprogesterone acetate relative to placebo. It is unknown whether this finding applies to younger postmenopausal women or to women taking estrogen alone therapy. (See CLINICAL PHARMACOLOGY, Clinical Studies.) Other doses of conjugated estrogens with medroxyprogesterone acetate, and other combinations and dosage forms of estrogens and progestins were not studied in the WHI clinical trials and, in the absence of comparable data, these risks should be assumed to be similar. -
Other Data Relevant to an Evaluation of Carcinogenicity and Its Mechanisms
COMBINED ESTROGEN−PROTESTOGEN MENOPAUSAL THERAPY 263 4. Other Data Relevant to an Evaluation of Carcinogenicity and its Mechanisms 4.1 Absorption, distribution, metabolism and excretion The distribution of progestogens is described in the monograph on Combined estro- gen–progestogen contraceptives. That of estrogens is described below. 4.1.1 Humans Little more has been discovered about the absorption and distribution of estrone, estradiol and estriol products and conjugated equine estrogens in humans since the previous evaluation (IARC, 1999). Greater progress has been made in the identification and characterization of the enzymes that are involved in estrogen metabolism and excre- tion. The various metabolites and the responsible enzymes, including genotypic varia- tions, are described below (see Figures 3 and 4). Sulfation and glucuronidation are the main metabolic reactions of estrogens in humans. (a) Metabolites (i) Estrogen sulfates Several members of the sulfotransferase (SULT) gene family can sulfate hydroxy- steroids, including estrogens. The importance of SULTs in estrogen conjugation is demons- trated by the observation that a major component of circulating estrogen is sulfated, i.e. estrone sulfate (reviewed by Pasqualini, 2004). In addition to the parent hormones, estrone and estradiol, SULTs can also conjugate their respective catechols and also methoxyestro- gens (Spink et al., 2000; Adjei & Weinshilboum, 2002). The resulting sulfated metabolites are more hydrophilic and can be excreted. In postmenopausal breast cancers, levels of estrone sulfate can reach 3.3 ± 1.9 pmol/g tissue, which is five to nine times higher than the corresponding plasma concentration (equating gram of tissue with millilitre of plasma) (Pasqualini et al., 1996). In contrast, levels of estrone sulfate in premenopausal breast tumours are two to four times lower than those in plasma. -
Ryeqo, INN: Relugolix / Estradiol / Norethisterone Acetate
ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions. 1. NAME OF THE MEDICINAL PRODUCT Ryeqo 40 mg/1 mg/0.5 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each film-coated tablet contains 40 mg relugolix, 1 mg estradiol (as hemihydrate), and 0.5 mg norethisterone acetate. Excipient with known effect Each film-coated tablet contains approximately 80 mg of lactose monohydrate. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablet. Light yellow to yellow, round film-coated tablet of 8 mm with “415” on one side and plain-faced on the other side. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Ryeqo is indicated for treatment of moderate to severe symptoms of uterine fibroids in adult women of reproductive age. 4.2 Posology and method of administration Posology One tablet of Ryeqo must be taken once daily, at about the same time with or without food. Tablets should be taken with some liquid as needed (see section 5.2). In patients with risk factors for osteoporosis or bone loss, a dual X-ray absorptiometry (DXA) is recommended prior to starting Ryeqo treatment (see section 4.4). When starting treatment, the first tablet must be taken within 5 days of the onset of menstrual bleeding. If treatment is initiated on another day of the menstrual cycle, irregular and/or heavy bleeding may initially occur. -
Estrone Screening Profile Estrone Is a Contaminant That Has Been Detected in Minnesota Waters
CONTAMINANTS OF EMERGING CONCERN PROGRAM Estrone Screening Profile Estrone is a contaminant that has been detected in Minnesota waters. The information in this profile was collected for the screening process of the Minnesota Department of Health’s Contaminants of Emerging Concern (CEC) program in November 2011. The chemicals nominated to the CEC program are screened and ranked based on their toxicity and presence in Minnesota waters. Based on these rankings, some chemicals are selected for a full review. CEC program staff have not selected estrone for a full review. Estrone Uses Potential Health Effects Estrone is a hormone produced naturally in humans Adverse health effects from prescribed doses of and animals. Estrone is a component of some estrone can include cancer, cardiovascular effects, medications used for the treatment of menopausal stroke, dementia, and others.5 Drinking water and premenopausal symptoms. Estrone is produced contaminated with low levels of estrone is not likely to naturally by men and women, but women produce pose a health risk. much higher levels than men. It is the most abundant Based on the screening assessment, a full review of natural estrogen produced by postmenopausal estrone may be possible; however, it is ranked lower women. The placenta also produces estrogens, than other nominated CEC chemicals at this time. including estrone, during pregnancy. References Estrone in the Environment 1. Ying G, Kookana RS, Ru YJ.2002. Occurrence and fate of Estrone enters the environment when it is excreted hormone steroids in the environment. Env Intl; 28:545. from humans and animals. The spreading of poultry http://www.lu.lv/ecotox/publikacijas-3-kursa- and cattle waste on agricultural land increases the risk studentiem/Steroid_hormones_EI.pdf 2.