Symptoms Of Estrogen Deficiency Research Articles

The Loss of Estradiol by Androgen Deprivation in Prostate Cancer Patients Shows the Importance of Estrogens in Males.

The role of estradiol (E2; an estrogen) in men needs to be more appreciated. In this review, we address the clinical situations that allow the study of the clinical consequences of E2 deficiency in men and discuss the effects of restoration of levels of this reproductive steroid hormone. In men with advanced prostate cancer (PCa) undergoing androgen deprivation therapy (ADT), E2 is suppressed along with testosterone, leading to side effects affecting the quality of life. These include hot flashes, arthralgia, fatigue, mood changes, cognition problems, weight gain, bone loss, and increased risk of cardiovascular disease. Transdermal E2 alone for ADT has shown equivalent testosterone suppression compared to gonadotropin-releasing hormone (GnRH) agonists while also preventing estrogen-deficiency side effects, including hot flashes and bone loss. Co-treatment of ADT with fetal estrogen estetrol (E4) has shown significant improvements of estrogen-deficiency symptoms. These observations emphasize the need to raise awareness of the importance of estrogens in men among clinicians and the lay public.

Saturated fatty acids and omega-3 polyunsaturated fatty acids improve metabolic parameters in ovariectomized female mice.

In menopausal and postmenopausal women, obesity, cardiovascular disease, osteoporosis and gut dysbiosis are induced by loss of ovarian 17β-estradiol (E2). Dietary fatty acid profile high in omega-6 polyunsaturated fatty acids (PUFAs), specifically linoleic acid (LA), and low in coconut oil saturated fatty acids (SFAs) and omega-3 PUFAs may worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or estradiol benzoate (EB)-treated ovariectomized C57BL/6J and transgenic fat-1 mice were fed high-fat diet (HFD, 45% kcal fat) with a high LA:SFA ratio (22.5%:8%; 22.5% LA diet) or a HFD with a low LA:SFA ratio (1%:31%; 1% LA) diet for a period of 14-15 weeks. EB treatment rescued obesity, glucose intolerance, and bone loss in OVX mice. fat-1 mice fed 1% LA diet mitigated weight gain and adiposity in Veh-treated OVX mice. fat-1 mice fed 22.5% LA diet had increased EE and activity as wheel running in EB-treated OVX mice. Except for EB treatment, coconut oil SFAs and omega-3 FAs can protect against glucose intolerance. Apparent improvement of insulin sensitivity was achieved by EB treatment in both WT and fat-1 mice fed 1% LA diet, while fat-1 mice fed 22.5% LA diet was protected against insulin resistance without EB treatment. Increase of relative abundance of gut microbial taxa as SCFA producers were associated with omega-3 FAs production and improved energy homeostasis. These data suggest that a balanced dietary FA profile containing coconut oil SFAs, and a lower ratio of omega-6/omega-3 FAs is a safer strategy for alleviating metabolic disorders during E2 deficiency.

Improvement of Estrogen Deficiency Symptoms by the Intake of Long-Term Fermented Soybeans (Doenjang) Rich in Bacillus Species through Modulating Gut Microbiota in Estrogen-Deficient Rats

Traditionally made doenjang (TMD) produced by the long-term fermentation of soybeans with salt may improve symptoms of estrogen deficiency. We aimed to evaluate the effects of four TMD types, containing low and high amounts of Bacillus species and biogenic amines (HBHA, HBLA, LBHA, and LBLA), on energy, glucose, and lipid metabolism, by altering the gut microbiota in estrogen-deficient ovariectomized (OVX) rats. Their mechanisms were also examined. The OVX rats were divided into the control, cooked soybean (CSB), HBHA, LBHA, HBLA, and LBLA groups. Sham-operated rats were the normal control group. Serum 17β-estradiol concentrations were similar among all OVX groups. Tail skin temperatures, which are indicative of hot flashes, were higher in the control than the HBHA and HBLA groups and were similar to the normal control group. Weight gain and visceral fat mass were lower in the TMD and CSB intake groups but not as low as in the normal control group. Lean body mass showed a trend opposite to that of visceral fat in the respective groups. The hepatic triglyceride content decreased with the TMD intake compared to the control and CSB groups. mRNA expressions of the peroxisome proliferator-activated receptor-γ (PPAR-γ) and carnitine palmitoyltransferase-1 in the TMD and CSB groups were as high as in the normal control group, and the PPAR-γ mRNA expression was more elevated in the HBLA group than in the normal control group. The morphology of the intestines improved in the TMD groups compared to the control, and the HBHA and HBLA groups showed an enhanced improvement compared to the CSB group. The HBHA, HBLA, and LBHA groups increased the α-diversity of the cecal microbiota compared to the control. Akkermenia and Lactobacillus were higher in the HBLA and LBLA groups compared to the control. The expression of the estrogen, forkhead box proteins of the class-O subgroup, and insulin-signaling pathways were lower in the control group, and HBHA and HBLA prevented their decrement. In conclusion, long-term treatment with TMD containing high amounts of Bacillus potentially improves estrogen deficiency symptoms more than unfermented soybeans.

Coconut Oil Saturated Fatty Acids Improved Energy Homeostasis but not Blood Pressure or Cognition in VCD-Treated Female Mice.

Obesity, cardiometabolic disease, cognitive decline, and osteoporosis are symptoms of postmenopause, which can be modeled using 4-vinylcyclohexene diepoxide (VCD)-treated mice to induce ovarian failure and estrogen deficiency combined with high-fat diet (HFD) feeding. The trend of replacing saturated fatty acids (SFAs), for example coconut oil, with seed oils that are high in polyunsaturated fatty acids, specifically linoleic acid (LA), may induce inflammation and gut dysbiosis, and worsen symptoms of estrogen deficiency. To investigate this hypothesis, vehicle (Veh)- or VCD-treated C57BL/6J mice were fed a HFD (45% kcal fat) with a high LA:SFA ratio (22.5%: 8%), referred to as the 22.5% LA diet, or a HFD with a low LA:SFA ratio (1%: 31%), referred to as 1% LA diet, for a period of 23 to 25 weeks. Compared with VCD-treated mice fed the 22.5% LA diet, VCD-treated mice fed the 1% LA diet showed lower weight gain and improved glucose tolerance. However, VCD-treated mice fed the 1% LA diet had higher blood pressure and showed evidence of spatial cognitive impairment. Mice fed the 1% LA or 22.5% LA diets showed gut microbial taxa changes that have been associated with a mix of both beneficial and unfavorable cognitive and metabolic phenotypes. Overall, these data suggest that consuming different types of dietary fat from a variety of sources, without overemphasis on any particular type, is the optimal approach for promoting metabolic health regardless of estrogen status.

PSAT217 Estrogen Deficiency as a Cause of Decreased 1- alpha - hydroxylase Activity

Abstract Case description A 40 year old woman receiving cholecalciferol therapy -10,000 IU, and alfacalcidol 1 mcg per day showed a 25 (OH) D increase to 351. 1 ng/mL (normal 65-100) with a normally high parathormone level of 33.5 pg/mL (normal 15-65). Clinically, symptoms of vitamin D deficiency - decreased immunity, decreased muscle mass and strength, depression, and symptoms of estrogen deficiency (hot flashes, scanty menstruation, hair loss) persisted against a high 25(OH)D background, so estrogen determination was performed in the steroid profile of saliva. Estradiol content was decreased - 3.45 pg/ml (norm 4.17 - 9.28), in connection with which transdermal estrogen therapy in a dose of 3.0 g was prescribed. Against the background of estrogen therapy, parathormone decreased from 33.5 to 22.4 pg/ml. Determination of 25(OH)D and estradiol in saliva was performed by mass spectrometry, determination of parathormone by ELISA. Discussion Vitamin D status depends on several factors, in particular on the activity of the enzyme 1 - alpha-hydroxylase (CYP27B1) in the kidney, which converts 25 (OH) D into the active form (1,25 - (OH)2 - D), which in turn depends on both parathormone and sex steroids (estrogen and androgens), determination of which is not a routine practice in vitamin D deficient patients. Elevated parathormone levels are considered a marker of vitamin D deficiency (secondary hyperparathyroidism). Decreased parathormone levels are considered a laboratory manifestation of vitamin D overdose. In this patient, there was no decrease in parathormone below the differential level of 25(OH)D in the background of high levels. Sex steroids increase the synthesis of calcitriol (D hormone, dihydrocholecalciferol 1,25 - (OH)2 - D) by activating the enzyme 1 - alpha - hydroxylase (CYP27B1) in the kidneys. In particular, estradiol deficiency exacerbates vitamin D deficiency. Conclusion Determination of 25(OH)D levels in patients with decreased 1 -alpha-hydroxylase activity leads to hypodiagnosis of vitamin D deficiency. In all patients with high 25(OH)D levels, the determination of parathormone as well as estrogens in saliva is necessary. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Modern therapy for vasomotor symptoms of climacteric syndrome

As a result of the age-related decline in reproductive function, during the perimenopausal and postmenopausal periods female patients experience an estrogen deficiency state. Due to this state, symptoms of estrogen deficiency, which are combined into the concept of “climacteric syndrome”, begin to manifest. Climacteric syndrome is a complex of vegetative-vascular, mental, and metabolic-endocrine disorders that develop in women not only due to decrease in estrogen synthesis, but also the general ageing of the body. Clinical manifestations of the climacteric syndrome have a certain priority of development. With a decrease of the hormonal function of the ovaries, vasomotor disorders step forward. They represent all forms of autonomic regulation disorders, such as hot flashes, arterial pressure and pulse liability, respiratory disorders, hyperhydrosis, chills, and many others. In this article, the greatest emphasis is placed on the issue of vasomotor disorders, in particular hot flashes, in women of the perimenopausal and postmenopausal periods. Attention is paid to the medical and social component of the issue discussed. Given the fact that today the life expectancy of people, including women, is significantly increasing in the developed countries, a large number of females are faced with the issue of menopausal syndrome. The clinical manifestations of menopause not only have an extremely negative impact on the women’s quality of life, but also lay the groundwork for the development of more severe somatic disorders. The article also considers in detail the frequency of hot flashes, and the pathogenetic mechanisms of their development. The “gold standard” for the treatment of patients suffering from vasomotor disorders is particularly detailed. Today, the menopausal hormone therapy is recognized as the most effective therapeutic approach, which, subject to a personalized approach to patients and the absence of contraindications to its prescription, demonstrates high protective capabilities.

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study

BackgroundAndrogen deprivation therapy (ADT) for prostate cancer (PCa) is accompanied by side effects affecting health-related quality of life (HRQL). ObjectiveTo assess the effects of the fetal estrogen estetrol (E4) on symptoms related to estrogen and androgen deficiency, and on HRQL measured using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Design, setting, and participantsThis was a phase 2, double-blind, randomized, placebo-controlled study in patients with advanced PCa. InterventionPatients receiving ADT were randomly assigned at a 2:1 ratio to daily treatment with a high dose of E4 (HDE4; n = 41) or placebo (n = 21) for 24 wk. Outcome measurements and statistical analysisThe primary outcome was the effect of HDE4 cotreatment on hot flushes (HFs). Secondary outcomes were the Q-Man questionnaire for evaluation of the effect on estrogen and androgen deficiency symptoms, and the FACT-P questionnaire for evaluating HRQL. Results and limitationsAt 24 wk, the number of patients experiencing HFs was significantly lower in the HDE4 group than in the placebo group (14.3% vs 60.0%; p < 0.001). HDE4 treatment was associated with lower incidence of night sweats, arthralgia, and fatigue, but more nipple tenderness and gynecomastia. At 24 wk, the mean HRQL score favored HDE4 over placebo for the FACT-P total score (122.2 ± 12.3 vs 118.7 ± 19.7) and for several other FACT subscales. ConclusionsDaily HDE4 coadministration almost completely prevented HFs in patients with advanced PCa treated with ADT. HDE4 also had positive effects on HRQL and counteracted other estrogen deficiency symptoms caused by ADT. These data support the dual efficacy concept of ADT and HDE4 to improve HRQL and increase the antitumor effect of ADT. Patient summaryFor patients on androgen deprivation therapy for advanced prostate cancer, cotreatment with a high dose of estetrol almost completely prevents the occurrence of hot flushes and improves quality of life and well-being, but nipple sensitivity and an increase in breast size may occur.

The British menopause society consensus statement on the management of estrogen deficiency symptoms, arthralgia and menopause diagnosis in women with treated for early breast cancer.

This guidance document by the British Menopause Society provides an overview of the management of women experiencing estrogen deficiency symptoms and arthralgia following a breast cancer diagnosis. It is now recommended breast cancer patients are referred to health care professionals with an expertise in menopause for management of such symptoms, which in turn often involves liaison with patients' breast cancer teams.1 However, as many women initially present to primary health care professionals for advice, this statement is aimed to support the latter in such consultations by providing information about symptom aetiology, current management strategies and controversies and identifying useful practice points. This is an updated version of the 2018 consensus statement prepared by Miss Jo Marsden Consultant Breast Surgeon, King's College Hospital, London, (retired), Mr Mike Marsh, Consultant Gynae-endocrinologist, King's College Hospital, London, Dr Anne Rigg, Consultant Medical Oncologist, Guy's and St Thomas' Hospital, London.

Особенности течения COVID-19 у женщин в пери- и постменопаузе. Роль менопаузальной гормональной терапии

A literature review on the effect of peri- and postmenopausal period on the course of novel coronavirus infection and post-COVID-19 syndrome was performed. The aspects of hormone replacement therapy against the background of therapy for COVID-19 and post-COVID-19 syndrome were studied. The postmenopausal period in women was found to be a risk factor for a more severe course of COVID-19. Estradiol may act as a protective factor for women with COVID-19 by regulating cellular and humoral immunity factors such as interleukin-2, -6, -8, tumor necrosis factor-α and C3. Prolonged course of COVID-19, persistence of its symptoms and development of severe post-COVID-19 syndrome are associated with female sex, with women in peri- and postmenopausal period being most vulnerable. Symptoms of estrogen deficiency and menopause may be similar to the manifestations of post-COVID-19 syndrome, and these conditions can coexist and aggravate each other. According to international experts, the use of hormone replacement therapy will help to improve the well-being of women, their quality of life, and relieve the symptoms typical of menopause and post-COVID-19 syndrome. Key words: coronavirus infection, COVID-19, menopause, post-COVID-19 syndrome, hormone replacement therapy, estrogen

Erxian Decoction, a Famous Chinese Medicine Formula, Ameliorate Depression- Like Behavior in Perimenopausal Mice.

The present study was performed in order to find out the anti-depression effect of Erxian Decoction in perimenopausal mice. Erxian Decoction (EXD) has been used in folk medicine for the treatment of perimenopausal syndrome, but it has not been researched on perimenopausal depression. The present study aimed to evaluate the effect of extraction of Erxian Decoction on perimenopausal depressive mice. In this study, female ICR mice were randomly divided into 6 groups: Low, medium and high dose of EXD groups (0.5, 1.5, and 4.5 g/kg), soy isoflavones group (250 mg/kg) and Sham group. The mice in the Sham group received sham surgery (within ovaries), and the others were excised with bilateral ovaries and exerted by 28-day chronic mild unpredictable stimulation for the establishment of a perimenopausal depression model. Behavioral tests showed that EXD could relieve depression symptoms and improve spatial memory in mice. Western blotting showed that EXD significantly up-regulated the expression of brain-derived neurotrophic factor (BDNF) and Bcl-2 in hippocampus and estrogen receptors (ERs) in the uterus and adrenals, protecting hippocampal tissue and antagonizing the symptoms of estrogen deficiency in mice, which was further proved within a uterine morphology test. In addition, EXD reduced the serum levels of follicle-stimulating hormone, luteinizing hormone, and interleukin- 6. These results indicated that EXD can regulate hormone secretion and recover hippocampal damage in perimenopausal depressed mice. Besides, it can antagonize the symptoms of ovarian hormone deficiency as well as relieve perimenopausal syndrome.

Antipsychotic medication for women with schizophrenia spectrum disorders.

There are significant differences between men and women in the efficacy and tolerability of antipsychotic drugs. Here, we provide a comprehensive overview of what is currently known about the pharmacokinetics and pharmacodynamics of antipsychotics in women with schizophrenia spectrum disorders (SSDs) and translate these insights into considerations for clinical practice. Slower drug absorption, metabolism and excretion in women all lead to higher plasma levels, which increase the risk for side-effects. Moreover, women reach higher dopamine receptor occupancy compared to men at similar serum levels, since oestrogens increase dopamine sensitivity. As current treatment guidelines are based on studies predominantly conducted in men, women are likely to be overmedicated by default. The risk of overmedicating generally increases when sex hormone levels are high (e.g. during ovulation and gestation), whereas higher doses may be required during low-hormonal phases (e.g. during menstruation and menopause). For premenopausal women, with the exceptions of quetiapine and lurasidone, doses of antipsychotics should be lower with largest adjustments required for olanzapine. Clinicians should be wary of side-effects that are particularly harmful in women, such as hyperprolactinaemia which can cause oestrogen deficiency and metabolic symptoms that may cause cardiovascular diseases. Given the protective effects of oestrogens on the course of SSD, oestrogen replacement therapy should be considered for postmenopausal patients, who are more vulnerable to side-effects and yet require higher dosages of most antipsychotics to reach similar efficacy. In conclusion, there is a need for tailored, female-specific prescription guidelines, which take into account adjustments required across different phases of life.

Amenorrhea rates in women treated with novel oral, continuous hormonal therapy of body identical 17β-estradiol and micronized progesterone

Introduction: Bleeding and spotting is a major reason of discontinuation of hormonal therapy (HT) among postmenopausal women (PW) who expect amenorrhea during that period of their lifetime. New oral combination therapy of 1 mg 17β-estradiol and 100 mg micronized progesterone (1 mg E2/100 mg P4) in a single softgel capsule is the first HT of naturally occurring E2 and P4 identical to human endogenous ovarian hormones (body-identical). It is approved in the US, Canada, and several EU countries; indicated in EU for the treatment of estrogen deficiency symptoms in PW with an intact uterus.

Salivary Estrogens Androgens and Aromatase Inhibitors by LC-MS/MS in Breast Cancer Patients Treated With Testosterone Pellets Combined With Aromatase Inhibitors

Introduction: High dose testosterone (T) has been used for treating hormone-sensitive breast cancers for many years. However, a drawback to T therapy is its propensity to convert to estradiol (E2) via aromatase, which can override the growth inhibitory effects of T and stimulate estrogen sensitive tumors. Aromatase is higher in some women than others, particularly those with active tumors, truncal obesity, and inflammatory conditions contributing to and caused by cancer. Oral aromatase inhibitors (AI) have been used to prevent conversion of T to E2. While this effectively reduces E2 burden, systemic oral AI require higher dosing, which often leads to severe side effects. As an alternative to oral AI therapy, researchers have found that T combined with a much lower dose of AI in a solitary pellet implant placed in the subcutaneous (SC) tissue, or alternatively, into the breast adjacent to a primary tumor, is effective in reducing tumor burden and maintaining a low systemic level of E2, while reducing the adverse side effects of very low E2. Study Design: In this case study we report on the use of an LC-MS/MS method to monitor salivary levels of E2, Estrone (E1), T, and the AIs Letrozole (LET) and Anastrozole (ANZ) following T + AI therapy in a breast cancer patient (intolerant of oral LET) with active (measurable) tumor in the breast and metastatic disease. Steroids and AIs were measured in saliva at baseline, 1 week, and 4 weeks after insertion of subcutaneous pellets containing ‘60 mg T + 4 mg ANZ’ and ‘60 mg T + 6 mg LET’. Results: LC-MS/MS (range values-pg/ml) for postmenopausal women, and baseline, week 1 and week 4 post treatment values for each steroid and AI were: E2: (range 0.3-0.9), 0.4, < 0.3, < 0.3; E1: (range 0.9-3.1), 1.0, <0.4, <0.4; T: (range 7-22), 6, 96, 48; ANZ: (range <4), < 4, 2063, 24; LET: (range <4), < 4, 744, 175. Self-reported (Pre/Post Therapy) estrogen deficiency symptoms such as hot flashes, night sweats, vaginal dryness, joint pain, and sleep disturbances were significantly improved post T+AI therapy. In addition, the intramammary tumor decreased in size > 95% by month 5. Summary: These results show that low-dose SC AI therapy (4-6 mg/2-3 months = 0.1 mg/day) with T (120 mg/2-3 months = 1-2 mg/day) increases T to supra-physiological levels, prevents T metabolism to estrogens E2 and E1, reduces estrogen deficiency symptoms, and has beneficial effects on tumor growth inhibition. Simultaneous testing of sex-steroids E2, E1, T, and aromatase inhibitors LET and ANZ by LC-MS/MS provides a convenient means to monitor the bioavailable levels of these analytes and adjust them as necessary to optimize therapeutic efficacy and reduce adverse side effects.

Sonographic Predictors Of Pelvic Organs In Women With Premature Ovarian Failure

Premature menopause is a pathological condition characterized by the cessation of the functional activity of the ovaries in women under the age of 40 and manifested by amenorrhea, high levels of gonadotropins in the blood, infertility and symptoms of estrogen deficiency. POF occurs on average in 1% of women. The exact nature of the disease remains unknown. The basis of this pathology, regardless of the etiological factor, is a decrease in the reserve of primordial follicles, which is unusual for this age period, up to its complete depletion and the formation of the afollicular type of POF. This condition is described as a "multifactorial syndrome" due to chromosomal abnormalities, genetic disorders, fermentopathies, infectious and iatrogenic factors.

From menarche to menopause

On September 11–12, 2020, in Kyiv hosted the International Women's Health Summit “From Menarche to Menopause” with the participation of leading foreign and domestic experts in the field of obstetrics and gynecology. The event was devoted to such topical topics as miscarriage, infertility, menstrual irregularities, menopausal hormone therapy (MHT).The current concern in clinical practice is not overuse of MHT, but it underutilization, and the fact that only a small number of women with impaired quality of life through menopausal symptoms receive treatment, despite that they perfectly fit the patient's profile for such therapy.All types of MHT are characterized by following effects: a positive effect on the cardiovascular system if MHT was start before 60 ages or in the first 10 years after menopause onset; the mortality rate from all causes is not increased in patients on MHT. The “ideal” MHT should relieve vasomotor symptoms, influence urogenital symptoms, prevent fractures and bone loss, protect the cardiovascular system and endometrium, and should not increase the risks of breast cancer, deep vein thrombosis and pulmonary embolism. Estradiol + dydrogesterone (Femoston®) scheme fits perfectly into these criteria. Femoston® is an oral MHT preparation that is effective in relieving symptoms of estrogen deficiency with a proven safety profile on the cardiovascular system and breast. This drug helps to reduce the manifestations of symptoms of estrogen deficiency, increase bone mineral density, and has a positive effect on metabolic processes. Numerous studies have shown that combination of estradiol + dydrogesterone is not only highly effective against menopausal symptoms, but also extremely important features, in particular, a proven safety profile for breast cancer.

The Mediterranean diet and menopausal health: An EMAS position statement

IntroductionGlobally, 985 million women are aged 50 and over, leading to increasing concerns about chronic conditions such as cardiovascular disease, osteoporosis, dementia, and cognitive decline, which can adversely affect quality of life and independent living. AimTo evaluate the evidence from observational studies and randomized trials on the effects of the Mediterranean diet on short- and long-term menopausal health: estrogen deficiency symptoms, cardiovascular disease, osteoporosis, cognitive and mental health, breast cancer, and all-cause mortality. Materials and methodsLiterature review and consensus of expert opinion. Summary recommendationsThe Mediterranean diet is a non-restrictive dietary pattern common in the olive-growing areas of the Mediterranean basin. It may improve vasomotor symptoms, cardiovascular risk factors such as blood pressure, cholesterol and blood glucose levels, as well as mood and symptoms of depression. Long-term adherence may: improve cardiovascular risk and events, and death; improve bone mineral density; prevent cognitive decline; and reduce the risk of breast cancer and all-cause mortality.

Uterine Fibroid Causing Hyperprolactinemia and Paradoxical Prolactin Rise with Dopamine Agonist: Case Report and Systematic Review

Hyperprolactinemia in premenopausal women often presents with amenorrhea, symptoms of estrogen deficiency and sub-fertility. After exclusion of other common causes and in the context of a normal pituitary MRI scan, hyperprolactinemia is typically deemed “idiopathic.” Here we present a case where excess prolactin secretion was attributed to a uterine fibroid and following myomectomy the hyperprolactinemia and its clinical sequelae resolved. Following 6 years of secondary infertility, a 41-year-old woman presented with secondary amenorrhea, expressible galactorrhea, and symptoms of estrogen deficiency. Prolactin levels were consistently raised (1300 mU/L to 2100 mU/L, reference interval < 600 mU/L), and repeated pituitary imaging demonstrated no pituitary abnormality. Prolactin levels demonstrated a paradoxical rise in response to dopamine agonist therapy (2000 mU/L to 5900 mU/L). Imaging demonstrated a uterine fibroid and the patient underwent myomectomy. Following myomectomy, prolactin levels became undetectable, galactorrhea and symptoms of estrogen deficiency resolved, menses returned, and a planned unassisted pregnancy followed. Ectopic prolactin secretion from uterine fibroids is a rare cause of hyperprolactinemia and can result in the same clinical sequelae as pituitary causes. As ectopic prolactin secretion is not under inhibitory control of dopamine, it is usually resistant to, or may rise in response to, dopamine agonist therapy. Prior to a diagnosis of “idiopathic” hyperprolactinemia, ectopic sources of prolactin should be considered.

Abstract P5-11-15: Estetrol for treatment of advanced ER+/HER2- breast cancer

Abstract Introduction: A high dose of the fetal estrogen estetrol (E4) is anticipated to have anti-tumor effects in patients with advanced, anti-estrogen resistant, ER+/HER2- breast cancer (BC). It will most likely also improve patient’s quality of life by reducing symptoms of estrogen deficiency such as hot flushes, arthralgia, sleep disturbances, vaginal dryness, mood changes and depression, bone loss and fractures and cognition. The ABCE4 study is performed in Germany in this patient population. The main objectives of the study are to assess safety and tolerability of three doses of E4, to determine anti-tumor response and to evaluate estrogen deficiency symptoms. Study design: This is a multi-center, open-label, phase IB/IIA, dose-escalation study with a 3 + 3 cohort design, whereby successive cohorts of 3 patients receive 20 mg, 40 mg and 60 mg E4 per day by oral administration. Dose limiting toxicity (DLT), safety and wellbeing are evaluated after 4, 8 and 12 weeks of treatment. Occurrence of DLT at completion of phase IB after 4 weeks treatment determines escalation to the next higher dose. Objective anti-tumor effects are assessed by computer tomography scanning and evaluated according to RECIST criteria before and after 12 weeks of treatment. Thereafter treatment may continue based on an evaluation of the patient and her treating physician. In view of the small numbers required for this study design no statistical testing was performed. Results: A total of 12 postmenopausal women with progressive, heavily pre-treated advanced BC have been enrolled. Nine patients completed Phase IB. One patient in the 20 mg group discontinued the study during Phase IIA due to disease progression after 9,5 weeks of E4 treatment. She died 3 weeks later. Eight patients completed both the Phase IB and IIA part of the study. None of the patients experienced a DLT. All three E4 doses were well tolerated by all patients. In total 38 adverse events were reported. Adverse events were mainly of mild or moderate intensity. The following 8 events were considered possibly related to E4 treatment: increased endometrial thickness, spotting (2 patients), dry skin, pruritus, edema, fatigue (2 patients), alopecia and acid regurgitation. Seven events fulfilled the criteria of seriousness from which one was considered to be related to E4 treatment. This patient experienced moderate vaginal bleeding after 36 weeks treatment with 20 mg E4 and was hospitalized for hysteroscopy and endometrial ablation with full recovery thereafter. Importantly five of the eight patients who completed treatment with E4 reported subjective improvement and “felt much better” than before the start of E4 treatment. This was described by one of the patients as: ‘”feeling less down and exhausted; instead feeling much more optimistic, powerful and positive when taking E4”. Five patients completing 12 weeks E4 treatment showed objective anti-tumor effects with stable disease (n=4) and one remission. All five continued E4 treatment. Tumor assessment after 24 weeks of E4 treatment showed again stable disease in 4 patients. Conclusion: We conclude that daily doses of 20 mg, 40 mg and 60 mg E4 are well tolerated without DLTs. The majority of patients experienced favorable subjective effects and four patients treated for 24 weeks or longer showed stable disease and tumor remission respectively. Treatment with E4 meets the criteria for further investigation and development of E4 as a new drug for the treatment of anti-estrogen resistant advanced breast cancer. Final dose selection of E4 will take place in September 2019. Citation Format: Marcus Schmidt, Arnd Hönig, Yvette Zimmerman, Carole Verhoeven, Katrin Almstedt, Marco Battista, Hans Georg Lenhard, Jan Krijgh, Herjan Coelingh Bennink. Estetrol for treatment of advanced ER+/HER2- breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-11-15.

British Menopause Society consensus statement on the management of estrogen deficiency symptoms, arthralgia and menopause diagnosis in women treated for early breast cancer.

This guidance document by the British Menopause Society provides an overview of the management of women experiencing estrogen deficiency symptoms and arthralgia following a breast cancer diagnosis. It is now recommended that breast cancer patients are referred to health care professionals with an expertise in menopause for the management of such symptoms, which in turn often involves liaison with patients' breast cancer teams. However, as many women initially present to primary health care professionals for advice, this statement is aimed to support the latter in such consultations by providing information about symptom aetiology, current management strategies and controversies and identifying useful practice points.

Soy Isoflavones Ameliorate Metabolic and Immunological Alterations of Ovariectomy in Female Wistar Rats: Antioxidant and Estrogen Sparing Potential.

Hormone replacement therapy (HRT) can alleviate estrogen deficiency symptoms especially during menopause. The present study aimed at investigating the effect of soy isoflavones as HRT on immunological and bone health-related parameters with a special focus on the interactions between immunological status and metabolism. Thirty healthy cyclic female Wistar rats were used in this experiment. Ten females were sham-operated, and 20 females were subjected to ovariectomy. Overiectomized (OVX) female rats were randomly divided into 2 groups: the control group (G1, OVX/casein) was fed a casein-based diet, and the second group (G2, OVX/soy) was fed a high soy isoflavone diet. Both groups were compared to a sham-operated group (G3, sham/casein). Treatments continued for 7 weeks. Feed intake, weight gain, and lymphoid organ relative weights were recorded. Some metabolic, immunological, and bone health-related parameters were measured. Moreover, nitric oxide (NO), malondialdehyde (MDA), and total antioxidant capacity (TAC) were determined. Bone histopathology and immunohistochemistry to estrogen receptor alpha (ERα) were done. Feeding soy to OVX females reduced feed intake, weight gain, relative lymphoid organ weight, and T-lymphocytes transformation. Soy isoflavone administration normalized nearly all metabolic and immunological parameters to a level comparable to the sham group via oxidative stress amelioration and bone ERα promotion. Soy isoflavones seemed to be good HRT in estrogen deprivation which modulated the appetite, weight gain, lipid profile, proinflammation, and bone turnover.