Withdrawal Of Hormone Replacement Therapy Research Articles

(209) Bipolar and Menopause: Case Reports of Late Onset Bipolar Disorder Following Acute Withdrawal of Hormone Replacement Therapy

(209) Bipolar and Menopause: Case Reports of Late Onset Bipolar Disorder Following Acute Withdrawal of Hormone Replacement Therapy

Successful Spontaneous Pregnancy and Live Birth in a Woman With Premature Ovarian Insufficiency and 10 Years of Amenorrhea: A Case Report

Background: Primary ovarian insufficiency (POI) is a devastating diagnosis for reproductive-aged women due to the associated infertility and other serious health consequences. Spontaneous pregnancy without hormone replacement therapy (HRT) and/or assisted reproductive technology (ART) rarely occurs in POI patients, particularly in those patients with long-term amenorrhea.Case: On March 4, 2019, a 31-year-old Chinese POI patient visited our hospital for a spontaneous pregnancy after 10 years of amenorrhea and discontinuation of HRT 4 years prior. The patient had menarche at the age of 13, with 3 years of regular menstruation followed by amenorrhea occurring at the age of 20. POI was diagnosed by several hospitals; chromosome examination revealed a normal 46, XX karyotype. Treatment with estradiol valerate and progesterone did lead to resumed menstruation, while amenorrhea resumed after withdrawal of HRT. The patient married at the age of 23 and tried to conceive by HRT until the age of 25; her beta-human chorionic gonadotropin (HCG), estrogen (E2), and progesterone levels were 32987.7~119151.4 mIU/ml, 671.0~>1,000 pg/mL, and 6.6~27.9 ng/ml, respectively. On March 22, 2019, ultrasonography showed an intrauterine pregnancy with a normally developed gestational sac sized 45 × 42 × 32 mm with a 17 mm crown-rump length. On October 29, a 3,400 g healthy girl baby was delivered; the patient had a spontaneous delivery with natural labor.Conclusion: Spontaneous pregnancy is possible in women with POI and 10 years of amenorrhea.

Mammographic Density Reduction as a Prognostic Marker for Postmenopausal Breast Cancer: Results Using a Joint Longitudinal-Survival Modeling Approach.

Previous studies have linked reductions in mammographic density after a breast cancer diagnosis to an improved prognosis. These studies focused on short-term change, using a 2-stage process, treating estimated change as a fixed covariate in a survival model. We propose the use of a joint longitudinal-survival model. This enables us to model long-term trends in density while accounting for dropout as well as for measurement error. We studied the change in mammographic density after a breast cancer diagnosis and its association with prognosis (measured by cause-specific mortality), overall and with respect to hormone replacement therapy and tamoxifen treatment. We included 1,740 women aged 50–74 years, diagnosed with breast cancer in Sweden during 1993–1995, with follow-up until 2008. They had a total of 6,317 mammographic density measures available from the first 5 years of follow-up, including baseline measures. We found that the impact of the withdrawal of hormone replacement therapy on density reduction was larger than that of tamoxifen treatment. Unlike previous studies, we found that there was an association between density reduction and survival, both for tamoxifen-treated women and women who were not treated with tamoxifen.

Abstract P5-08-31: Withdrawal of exogenous hormones affects prognostic multigene signature results in early luminal breast cancer

Abstract Background Early breast cancer (BC) outcomes are mainly estimated based on clinicopathological parameters and rarely include proliferation markers: (Ki-67), and multigene signatures (MGS), which are typically measured in tumors from resection specimens (RS). We believe that tumor proliferation can change within days of anti-estrogen use. However, little is known how proliferation changes after withdrawal of hormone replacement therapy (HRT) or oral anti-conception (OAC) after a core needle biopsy (CNB) shows BC. Hence, this study compares the Ki-67 labeling index and the MGS results in CNB and RS collected from a cohort of patients under OAC/HRT. Patients and Methods This retrospective study included consecutive women diagnosed with a grade 1-2, any pTN0-1, primary operable estrogen receptor-positive, human epidermal growth factor receptor 2-negative, and invasive ductal carcinoma between January 2013 and July 2014 at the Multidisciplinary Breast Center of University Hospitals Leuven were selected from a prospectively managed database. Ki-67 staining was performed on RS (Ki-67RS) to compare those who used HRT/OAC for at least 3 months at diagnosis and those not using OAC/HRT at diagnosis. OAC/HRT was always stopped between CNB and RS. Subsequently, we compared Ki-67 of the CNB (Ki-67CNB) with the matched RS in 15 patients with a low Ki-67RS (14%) stopping OAC/HRT after CNB; revised standard pathology confirmed absence of tumor heterogeneity in all samples. In addition, in a subset of patients (≥50 years, Ki-67RS ≤5%) we compared Ki-67 index and MGS results (MammaPrint (MP) and BluePrint, Agendia) from the CNB versus RS. Results 193 patients with a known Ki-67RS were included; 38 patients (mean age of 55 years) were on OAC/HRT at CNB and 155 patients (mean age of 64 years) were not. The median time between stopping OAC/HRT and resection was 23 days (range 8-48 days). Ki-67RS was <6%, 6-14% and ≥15% in 30.0%, 36.8% and 33.2% in the whole group of patients, respectively. These figures were 44.7%, 44.7% and 10.5% in patients on OAC/HRT at CNB diagnosis and 26.5%, 34.8% and 38.7% in patients not on OAC/HRT. This difference was significant (p<0.05) for patients ≥50 years on HRT at CNB diagnosis. Four of 15 patients, which stopped OAC/HRT after the CNB (26.7%), showed a low Ki-67RS (≤14%) and had a high matched Ki-67CNB (≥15%). In another subset of four out of 15 patients we compared CNB and RS (table1) where we observed changes in both Ki-67 and MGS. MP and Ki-67 results from matched CNB and RS. CNBRSPatientKi-67 (%)MP indexKi-67 (%)MP index150.371-20.31280.1150.043100.0650.03425-0.702-0.13Low risk is defined as MP index ≥0.0575 and/or Ki-67 ≤14. Conclusion Women on OAC/HRT, at diagnosis of an early luminal BC, are more likely to have a lower Ki-67RS as those not using OAC/HRT. Our findings are likely explained by a sudden decrease in sex steroids after BC diagnosis, resulting in lower proliferation markers. As such, a lower hormonal environment by withdrawing HRT/OAC at BC diagnosis might underestimate proliferation markers used for prognostic and predictive purposes. Therefore we are currently testing this hypothesis in larger cohorts. Citation Format: Jongen L, De Vries P, Van Asten K, Lintermans A, Laenen A, Wildiers H, Floris G, Neven P. Withdrawal of exogenous hormones affects prognostic multigene signature results in early luminal breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-08-31.

Manic Episode Precipitated by Withdrawal of Hormone Replacement Therapy in Severe Hypothyroidism

Manic Episode Precipitated by Withdrawal of Hormone Replacement Therapy in Severe Hypothyroidism

Sequentially combined estradiol valerate plus levonorgestrel therapy decreases 18:1 trans-fatty acid content of plasma lipids in healthy postmenopausal women

Trans-fatty acids (TFA) have been classified as atherogenic dietary constituents but the effect of hormone replacement therapy (HRT) on their concentrations is not known. We used a washout protocol to study the effect of long-term estrogen and combined estrogen–progestin HRT on plasma elaidate (18:1t), which is the trans isomer of oleate and the major TFA in the diet. The study group comprised 15 women receiving estradiol valerate HRT and 15 women receiving combined HRT with estradiol valerate and levonorgestrel. The concentrations of elaidate in plasma phospholipids, cholesteryl esters and triglycerides were determined by gas chromatography. At baseline, the total plasma elaidate concentration was lower in the combined HRT group than in the estradiol valerate HRT group (p < 0.01). In the combined HRT group, the concentration of elaidate increased significantly after withdrawal of HRT (p < 0.001) and decreased again to the baseline level after restart of therapy (p < 0.001). These changes were due to decreases in the concentrations of phospholipids and triglycerides; in phospholipids there was also a proportional decrease of elaidate. There were no changes in elaidate in women receiving estradiol valerate alone. Our results suggest that long-term combined HRT treatment decreases plasma TFA, which is not achieved by estrogen alone.

Effect of withdrawal of hormone replacement therapy on bone mass and bone turnover: the OFELY study

The beneficial effects of hormone replacement therapy (HRT) on bone mineral density (BMD) and bone turnover are well documented but whether HRT withdrawal is followed by an accelerated rate of bone loss is still controversial. We analyzed 26 women who have withdrawn HRT during a 6-year follow-up of the OFELY cohort. They were compared with three groups of women from the same cohort: One hundred four healthy postmenopausal women who continued HRT during the 6-year follow-up, 78 untreated postmenopausal women matched for age, and 31 untreated women within 5 years of menopause. Bone markers [serum osteocalcin (Intact OC), bone alkaline phosphatase (Bone ALP), and serum CTX] were performed annually during 4 years and bone mineral density (BMD) was measured at the forearm (DXA) during 6 years. Withdrawal of HRT was followed by a significant bone loss with an annual rate ranged from −0.7 to −1.6% at the radius according to the skeletal site and by a marked increase of bone markers after 6 months: +36 % for osteocalcin, +23% for bone alkaline phosphatase, and +120% for serum CTX ( P < 0.05 to P < 0.001). In contrast, in the HRT continuing group, there was no bone loss and no substantial change of bone markers over 4 years. The rate of bone loss after withdrawal of HRT was significantly greater than in postmenopausal women matched for age who never received HRT (2.2 to 2.8 times higher according to the radius area) and not different as compared to the accelerated bone loss observed in untreated women within 5 years of menopause. We conclude that in postmenopausal women who have been on HRT for 6 years, cessation of treatment results in a rapid increase of bone turnover and a rate of bone loss similar to early postmenopausal women during the subsequent 4 years and greater than untreated women of the same age.

Hormone replacement therapy: to use or not to use?

The main indication for hormone replacement therapy (HRT) is to control menopausal symptoms and improve quality of life. Ideally, withdrawal of HRT should be attempted after 4-5 years of therapy. HRT reduces fracture risk and remains appropriate therapy for osteoporosis, particularly in women with symptoms. HRT is not appropriate for primary or secondary cardioprotection. HRT leads to a small increase in breast cancer incidence, which increases with duration of therapy and age. HRT increases the risk of thromboembolism. Patient management and therapy should be reviewed annually with risk-benefit counselling.

Prevention of postmenopausal bone loss with exchange for short-term HRT for 1α-hydroxycholecalciferol

Objective: The present study investigated bone turnover with exchange of hormone replacement therapy (HRT) by treatment with 1α-hydroxycholecalciferol in early postmenopausal women. Methods: Subjects included a total of 75 postmenopausal women between 49 and 59 years of age who visited the Department of Obstetrics and Gynecology at Osaka Medical College Hospital for regular gynecological checkups and menopausal disorder, postmenopausal osteoporosis or hyperlipidemia, and were diagnosed with menopausal disorder or osteopenia. Changes in bone turnover and vertebral bone mineral density (BMD) in 28 patients who had undergone HRT; conjugated equine estrogen 0.625 mg daily and medroxyprogesterone acetate 2.5 mg daily) for at least 2 years and then switched to 1α-hydroxycholecalciferol (0.5 μg orally twice daily) and in 26 patients who were observed without drug administration after discontinuation of HRT were compared with those in 37 patients who continued HRT. BMD of the lumbar spine (L2–4) was determined using Dual Energy X-ray Absorptiometry. Results: While we observed a significant decrease in vertebral bone mass in the HRT-no medication group at 12 months ( P=0.049) and 18 months ( P=0.013), there was no significant decrease in vertebral bone mass in either the continuous HRT group or the group with change of HRT to 1α-hydroxycholecalciferol. In the group with change of HRT to 1α-hydroxycholecalciferol, although urinary pyridinoline level increased significantly from the baseline level throughout the study period ( P<0.05), serum propeptide of type-1 procollagen (P1CP) level also increased significantly from the baseline level throughout this period ( P<0.001). Furthermore, significant increase from the baseline value ( P<0.01) was observed in serum osteocalcin level at 6, 12 and 18 months. Conclusions: These results indicate that switching to 1α-hydroxycholecalciferol therapy after short-term HRT increased both bone resorption and bone formation, and permitted maintenance of increase in bone mass due to HRT for at least 18 months, though this switching accelerated bone turnover. This may have occurred because stimulation of bone formation induced by HRT was maintained by 1α-hydroxycholecalciferol, though bone turnover was slightly promoted because of withdrawal of HRT. This method was thus found to be very effective in preventing bone loss in patients who have discontinued HRT and are considered relatively contraindicated for use of estrogen.

Complete Resolution of Metastatic Breast Cancer by Withdrawal of Hormone Replacement Therapy

We report the case history of a patient with a known history of locally recurrent breast cancer, who developed metastatic disease while taking hormone replacement therapy (HRT). She underwent complete radiographic resolution of disease with no treatment other than cessation of the HRT.

Withdrawal of hormone replacement therapy is associated with significant vertebral bone loss in postmenopausal women.

This study aimed to assess the changes in vertebral bone mineral density (BMD) after cessation of hormone replacement therapy (HRT) in postmenopausal women who had been treated on a long-term basis. Fifty healthy postmenopausal women who had been followed both during the course of HRT and after cessation of treatment in our menopause clinic were included in this study. All women had started HRT within the first 3 years after the postmenopause and had received HRT (either 1.5 mg/day of 17 beta-estradiol given percutaneously or 50 micrograms/day of 17 beta-estradiol given as a transdermal patch, combined in all women with natural progesterone or a 19-norprogesterone derivative) for a mean 5 +/- 2.4 years. In all women, vertebral BMD was assessed during the course of HRT up to the last 6 months before estrogen withdrawal, then at least once within the first 18 months after cessation of treatment. Of the initial population, 30 women were additionally reviewed later on and up to 8 years after cessation of treatment (mean duration of follow-up for the whole population: 3.9 +/- 1.7 years). Rates of changes in vertebral BMD were compared with those determined in a group of healthy untreated women who had been followed within the first years of postmenopause during the same time period as the study population. In the study group, bone loss was found to accelerate within the first 2 years after HRT withdrawal and the annual rate of loss was identical to that which occurs within the first 2 years of postmenopause in untreated women (-1.64% +/- 1.3% vs -1.52 +/- 0.9%, NS). Beyond this first 2-year time period, the annual rate of bone loss decreased as a function of time following cessation of treatment, as was observed following the menopause in untreated women (between 3 and 5 years: -0.83% + 1.35% in the study group vs -0.70% +/- 0.8% in the control group, NS). On average, 3 years after cessation of HRT mean vertebral BMD when expressed as a Z-score was significantly higher (-0.13 vs -0.89, p < 0.01) than at baseline, before HRT was started, which suggested a lasting beneficial effect on bone mass. However, even though our findings do not support the hypothesis that bone loss might continue to be accelerated several years after cessation of treatment we cannot fully address the question as to whether any residual benefit on bone mass over a longer period of time may be observed. In conclusion, the pattern of bone loss observed after cessation of estrogen therapy was found to be comparable to that which occurs in younger women within the first years after the menopause. Such a pattern needs to be kept in mind when the decision to stop HRT is taken, especially in women who were given HRT to prevent osteoporosis. The issue of assessing their risk of fracture several years after cessation of treatment thus needs to be addressed.

Complete Resolution of Metastatic Breast Cancer by Withdrawal of Hormone Replacement Therapy

Complete Resolution of Metastatic Breast Cancer by Withdrawal of Hormone Replacement Therapy