Cessation Of Hormone Therapy Research Articles

Case Series: Severe meibomian gland loss in polycystic ovarian syndrome patients on estrogen-progesterone therapy: A case series

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

Evaluating the effects of hormone therapy termination on skeletal muscle and physical independence in postmenopausal women.

In women, the age-related decline in skeletal muscle structure and function is accelerated after menopause, which implicates the role of decreased circulating estrogen levels. Indeed, boosting estrogen, by means of postmenopausal hormone therapy (HT), generally proves beneficial to skeletal muscle. The evidence regarding whether these benefits persist even after cessation of HT is limited, nor is it clear how physical behavior (PB) impacts on benefits. Hence, this exploratory study focused on the interplay between HT administration/cessation, PB and in vivo skeletal muscle structure and function. Fifty healthy women (≥60 y) were included; 19 had an HT administration history (≥9 mo, with now ~8-y hiatus in treatment) and 31 no such history. On seven continuous days, PB data were collected using triaxial accelerometry and analyzed using compositional data analysis. Gastrocnemius medialis muscle volume, architecture, and function were determined using ultrasonography, electromyography, dual x-ray absorptiometry, and dynamometry. Current serum estradiol levels were measured using ELISA. Only fascicle length and duration of HT administration were positively associated. With respect to PB levels, we found a pattern suggesting greater vitality (higher physical activity and lower sedentarism) in previous HT users, compared with nonusers, despite the two groups currently no longer exhibiting significantly different levels of circulating estradiol. After an 8-year hiatus in treatment, HT provides limited advantages in gastrocnemius medialis muscle properties. Interestingly, it perhaps enhances vitality despite prolonged cessation, which in the longer term would facilitate greater physical independence, especially considering the association of sedentary behavior with greater frailty.

Abstract PO3-04-03: Drug Holidays in Patients with HER-2 Positive Metastatic Breast Cancer

Abstract Background Treatment of HER-2 positive metastatic breast cancer (MBC) involves the use of HER-2-targeted therapy in combination with cytotoxic chemotherapy and/or hormone therapy. Treatment duration for HER2-targeted agents is not standardized, and patients are often kept on these drugs indefinitely. Drug holidays can be initiated due to poor tolerance of drug or can be considered when trying to limit drug toxicity. Our study aims to determine the safety of utilizing drug holidays for patients receiving HER2-targeted therapies and the effect on overall survival and disease progression. Methods Study Design This retrospective study included patients who were diagnosed with metastatic HER2 positive breast cancer and had complete clinical and survival data available within UPMC Magee Women’s Hospital. The patients were divided into two groups based on whether they had a drug holiday or not. A drug holiday was defined as the temporary cessation of antiHER2 therapy for a minimum of three months in patients receiving HER2-targeted treatments. This involved the discontinuation of earlier- and later-line medications without considering the cessation of hormone therapy. Statistical Analysis The chi-square test or Fisher's exact test was used to compare categorical variables and the Mann-Whitney U test was used to compare continuous variables. The results were reported as proportions for categorical variables and as medians with 25th-75th percentiles for continuous variables. Survival rates and Hazard ratios were estimated using Kaplan-Meier log-rank tests and Cox models, respectively. The significance level was set at p < 0.05 for all analyses. Results 83 patients with HER2+ MBC treated with HER2-targeted therapy were identified, of which 54 patients were in the drug holiday group. Of noted patient variables, there was no significant difference in the tumor histology, distribution of estrogen receptor (ER) status (p= 0.38) and progesterone receptor (PR) status (p = 0.64). The use of hormonotherapy, immunotherapy, radiotherapy to the primary tumor, and radiotherapy to metastasis did not significantly differ between the two groups (p > 0.05 for all comparisons). Subgroup analysis was conducted within the hormonotherapy subgroup to assess the survival difference in the no drug holiday group and to evaluate the impact of drug holiday on antiHER2 therapy cessation while continuing hormonotherapy. There was a trend towards a higher proportion of patients who were deceased in the no drug holiday group (62%) compared to the drug holiday group (42%), although this difference did not reach statistical significance (p = 0.16). The disease status differed significantly between the two groups (p < 0.0001). In the no-drug holiday group, 72% of patients had progressive disease, while 20% had stable disease with the anti-HER2 therapy and 7% had no-evidence of disease. In contrast, the drug holiday group had a higher proportion of patients with no-evidence of disease (48%) compared to progressive disease (38%) and stable disease (14%). The drug holiday group demonstrated higher overall survival (61% with median follow-up 1719 days 25th-75th percentile: 963-2222) compared to the no drug holiday group (39% with median follow-up time of 803 days 25th-75th percentile: 216-1510) (p= 0.04). Conclusion Overall, our findings suggest that utilization of a drug holiday in stable and NED HER2+ MBC is not associated with decreased survival. Analysis within the hormonotherapy subgroup indicated no survival difference in the drug holiday group, highlighting the potential for cessation of antiHER2 therapy while continuing hormonotherapy in this specific subgroup. However further prospective studies with long drug holiday intervals, larger sample size, and control of other potential confounding factors are needed to validate these results. Citation Format: Saba Kurtom, Kazim Senol, Qurat Ul Ain Sabih, Efe Sezgin, Adam Brufsky, Vikram Gorantla, Shannon Puhalla, Atilla Soran. Drug Holidays in Patients with HER-2 Positive Metastatic Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-04-03.

Severe meibomian gland loss in polycystic ovarian syndrome patients on estrogen-progesterone therapy: A case series.

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

Efficacy of minodronic acid for the prevention of osteoporosis in premenopausal women with gynaecologic disease who undergo bilateral oophorectomy: a single-centre, non-randomised controlled, experimental study

We evaluated the efficacy of minodronic acid for osteoporosis prevention after bilateral oophorectomy for gynaecologic disease in premenopausal women. Bone mineral density (BMD) and young adult mean (YAM) data from the lumbar vertebrae and femur and bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5 b (TRACP 5 b) data were obtained for 101 patients. The primary endpoint was the efficacy of minodronic acid for osteoporosis prevention. Fifty-five and 31 patients were assigned to medication and no medication groups, respectively. The decrease in BMD and YAM and the increase in BAP/TRACP-5b were significantly more suppressed in the medication group. There were no significant between-group differences in age at oophorectomy, cancer type, body mass index (BMI), and adjuvant therapy. There were no adverse events due to minodronic acid. Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. Impact statement What is already known on this subject? Although the current strategy for osteoporosis prevention after premenopausal bilateral oophorectomy (b-OVX) is hormone therapy (HT), there is no consensus on the treatment duration or adverse events. What do the results of this study add? Therefore, we planned a prospective study to evaluate the efficacy of prophylactic treatment for osteoporosis after b-OVX in premenopausal women with gynaecologic disease using minodronic acid, an oral bisphosphonate, which have a strong evidence of the treatment for osteoporosis. The result showed minodronic acid significantly suppressed the decrease in bone mineral density (BMD) and young adult mean (YAM) and the increase in bone alkaline phosphatase (BAP)/tartrate-resistant acid phosphatase 5b (TRACP 5b). Minodronic acid may prevent osteoporosis after oophorectomy in premenopausal women with gynaecologic disease, independent of age at oophorectomy, cancer type, BMI, or adjuvant therapy. What are the implications of these findings for clinical practice and/or further research? Minodronic acid treatment for osteoporosis prevention after premenopausal b-OVX may be effective as a therapeutic agent after the cessation of HT, or alternative for patients who are contraindicated for HT in breast cancer and thrombosis and should be administered with caution with a history of uterine or ovarian cancer.

Risk for Venous Thromboembolism in Transgender Patients Undergoing Cross-Sex Hormone Treatment: A Systematic Review

BackgroundFeminizing and masculinizing hormone treatments are established components of management in transgender patients. Exogenous hormones have been associated with hemostatic effects, which are well-studied in cis-gender individuals on hormone replacement therapy (HRT). Unfortunately, comprehensive understanding of their effects on venous thromboembolism (VTE) risk in the transgender population is lacking. AimThis manuscript aims to identify the risk of VTE among transgender individuals undergoing cross-sex hormone therapy. MethodsA Systematic review of the literature was performed in March 2020 for studies reporting VTE rates in transgender patients undergoing hormone treatment and rates in cis-gender patients on HRT. Data regarding demographics, hormone therapy, and VTE incidence were collected and pooled for analysis. OutcomeThe primary outcome of interest was the development of a VTE event in association with concurrent hormone administration. ResultsOverall, 22 studies were included with 11 reporting VTE rates among transgender patients, 6 in cis-female patients, and 5 in cis-male patients. Data from 9,180 transgender patients (6,068 assigned male at birth [AMAB] and 3,112 assigned female at birth [AFAB]) undergoing hormone treatment and 103,713 cis-gender patients (18,748 female and 84,965 male) undergoing HRT were pooled. The incidence of VTE was higher in AMAB patients compared to AFAB patients (42.8 vs 10.8 VTE per 10,000 patient years; P = .02). The rate of VTE incidences in AMAB patients appears similar or higher than the rate demonstrated in cis-females on HRT. VTE incidence in AFAB patients, however, is similar to the published rates in cis-males on HRT. Clinical ImplicationsAMAB patients on hormone therapy have higher VTE rates than AFAB patients. AMAB and AFAB patients may have similar VTE incidence to cis-female and cis-male patients on hormone replacement therapy, respectively. Strengths & LimitationsThis is the first study to aggregate and quantify the development of VTE events in association with hormone therapy in transgender patients. It places these values in the context of rates published in more widely studied populations. It is limited by its retrospective data and heterogenic data. ConclusionSurgical planning regarding perioperative and postoperative VTE prophylaxis or cessation of hormone therapy should take into account each patient's Caprini risk assessment and the nature of each intervention.Kotamarti VS, Greige N, Heiman AJ, et al. Risk for Venous Thromboembolism in Transgender Patients Undergoing Cross-Sex Hormone Treatment: A Systematic Review. J Sex Med 2021;18:1280–1291.

Renal Transplantation and Renovascular Hypertension.

dermal estrogen: RR 1.68, 95% CI 1.41, 2.00; oral estrogen with progestin: RR 1.34, 95% CI 1.24, 1.44; transdermal estrogen with progestin: RR 1.46, 95% CI 1.16, 1.84). There was little risk after the cessation of hormones (RR 1.14, 95% CI 1.06, 1.23) and a decreasing risk of incontinence with increasing time since last hormone use; 10 years after stopping hormones, the risk was identical in women who had and had never taken hormone therapy (RR 1.02, 95% CI 0.91, 1.14). CONCLUSION: Postmenopausal hormone therapy appears to increase risk of developing urinary incontinence. This risk does not vary by route of administration, type of hormones, or dose taken, but is diminished upon cessation of use. Editorial Comment: This large study supports the randomized trials which have indicated that hormone therapy does not improve urinary symptoms. In fact,there was a significant increase in the risk of developing incontinence over 4 years in those taking postmenopausal hormone therapy at baseline,and this risk was similar for users of estrogen alone and estrogen combined with progestin,as well as users of oral or transdermal estrogen. The elevated risk was evident for short-term and long-term users but decreased after cessation of hormone therapy. Symptoms of stress and urge incontinence were not separated,however—a shortcoming of the study,as it is certainly possible that one type could be affected and not the other,and it is even possible that one type could be benefited. The authors acknowledge this in their discussion,and also the fact that (1) all information on hormone therapy and incontinence is self-reported,and (2) in an observational study it is possible that results are due to confounding but they point out that this potential is reduced because health professionals in this subject all had good access to health care and sound health knowledge regardless of their hormone use.

Voice Change Following Testosterone Supplementation in Women: A Multi-Institutional Case Series

To describe voice changes as a result of the off-label use of androgen supplementation in women. A multi-institutional retrospective consecutive case series identified women taking androgen supplementation who presented to voice clinics at two institutions with a chief complaint of voice change between 2014 and 2019. Age, occupation, hormone therapy, indication, Voice Handicap Index-10, fundamental frequency, semitone pitch range, testosterone blood level, treatment undertaken, and long-term outcome were collected. Nine women presented with voice change after initiation of androgen hormone supplementation. The mean age was 55 and three patients were performers. All patients underwent hormone therapy with testosterone supplementation, most commonly subcutaneous testosterone pellets. Six patients (67%) were being treated for menopause symptoms, one patient for decreased libido, one patient for breast cancer, and one patient who desired additional muscle gain. Time of symptom onset after hormone therapy initiation was highly variable, ranging from 0 to 48 months with a mean of 15 months. Mean Voice Handicap Index-10 was 21, mean fundamental frequency at comfortable speaking level was 155 Hz and mean semitone pitch range was 22 semitones. Two patients had markedly elevated serum total testosterone levels. Hormone therapy discontinuation and voice therapy were recommended in six (67%) patients each. Five patients returned for follow-up after treatment and noted some subjective benefit. Female patients treated with androgen supplementation may experience unintended voice changes, most prominently reduction in fundamental frequency. Although some benefit may be obtained from voice therapy and cessation of hormone therapy, voice changes may be permanent. Caution should be exercised when prescribing these medications to women.

EMAS position statement: Predictors of premature and early natural menopause

IntroductionWhile the associations of genetic, reproductive and environmental factors with the timing of natural menopause have been extensively investigated, few epidemiological studies have specifically examined their association with premature (<40 years) or early natural menopause (40–45 years). AimThe aim of this position statement is to provide evidence on the predictors of premature and early natural menopause, as well as recommendations for the management of premature and early menopause and future research. Materials and methodsLiterature review and consensus of expert opinion. Results and conclusionsStrong genetic predictors of premature and early menopause include a family history of premature or early menopause, being a child of a multiple pregnancy and some specific genetic variants. Women with early menarche and nulliparity or low parity are also at a higher risk of experiencing premature or early menopause. Cigarette smoking (with a strong dose–response effect) and being underweight have been consistently associated with premature and early menopause. Current guidelines for the management of premature and early menopause mainly focus on early initiation of hormone therapy (HT) and continued treatment until the woman reaches the average age at menopause (50–52 years). We suggest that clinicians and health professionals consider the age at menopause of the relevant region or ethnic group as part of the assessment for the timing of HT cessation. In addition, there should be early monitoring of women with a family history of early menopause, who are a child of a multiple pregnancy, or who have had early menarche (especially those who have had no children). As part of preventive health strategies, women should be encouraged to quit smoking (preferably before the age of 30 years) and maintain optimal weight in order to reduce their risk of premature or early menopause.

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Aortic hemodynamics in postmenopausal women following cessation of hormone therapy.

Central (aortic) blood pressure and aortic pulse wave characteristics are measures of cardiovascular health, predictive of cardiovascular mortality. Previous studies have compared aortic hemodynamics in women who do and do not take menopausal hormone therapy, but characteristics of these parameters following cessation of treatment have not been defined. Therefore, the purpose of this study was to define aortic pulse wave characteristics in postmenopausal women with and without a history of menopausal hormone therapy use. Pulse wave analysis was conducted on 67 women who had participated in the randomized, double‐blind, placebo‐controlled Kronos Early Estrogen Prevention Study (KEEPS), 3 years subsequent to the four‐year treatment period. Treatment was oral conjugated equine estrogen (0.45 mg/day; n = 18); transdermal 17β‐estradiol (50 μg/day; n = 23) each with oral micronized progesterone (Prometrium 200 mg); and placebo pills and patch (n = 26). At post‐treatment, median age (60 years) and body mass index (27 kg/m2) did not differ across prior treatment assignment. Aortic blood pressures (median systolic 115 mm Hg and diastolic 76 mm Hg) and augmentation index (median 33%) did not differ among women across prior treatment assignment. These results suggest that these doses and formulations of menopausal hormone therapy had no long‐term effects on central vascular function 3 years after cessation of treatment.

Fracture incidence in pre- and postmenopausal women after completion of adjuvant hormonal therapy for breast cancer

IntroductionAlthough the effect of hormonal therapy (HT) on fracture risk during treatment of breast cancer is established, information about fracture incidence after completion of HT is scarce. In this hospital based observational study we evaluated fracture rates after completion of HT in pre- and postmenopausal women with breast cancer. MethodsAll women diagnosed with breast cancer in the VieCuri Medical Center between 1998 and 2005 who started adjuvant HT with aromatase inhibitors or tamoxifen were included (n = 289). Data on fracture rate, fracture type and risk factors for fracture after completion of HT were collected. ResultsThe overall fracture rate was 12% in pre- and 15% in postmenopausal women respectively during an average follow-up of 3.1 ± 2.9 years. The number of patients with at least one fracture was 41 (14%). There was no difference in fracture rates between different types of HT (P = 0.15). The most common types of fractures were toe/finger fractures in premenopausal- and hip and major fractures in postmenopausal women. Median time to first fracture was shorter in premenopausal women (1.4 years, IQR 0.2–3.5) than in postmenopausal women (2.4 years, IQR 0.7–5.1, P = 0.01). A history of previous fracture was a significant risk factor for fracture in postmenopausal women (HR 3.9, 95% CI 1.3–11.7). ConclusionFracture rates in the first years after cessation of HT for breast cancer were 12% and 15% for pre- and postmenopausal women respectively. The most common fractures in postmenopausal women were hip and major fractures.

Management of Hepatocellular Adenoma: Recent Advances

Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs more frequently in young women with a history of prolonged use of oral contraceptives. Surgical resection is considered because of the risk of hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA is a heterogeneous disease comprising 3 subtypes with distinct molecular and complication profiles. The inflammatory or telangiectatic subtype is at increased risk for hemorrhage, the β-catenin-activated subtype is at increased risk for malignant transformation, and the hepatocyte nuclear factor-1α-inactivated or steatotic subtype is at the least risk for complications. One-third of the patients with HCA have multiple tumors on imaging with no increased risk of complications. Magnetic resonance imaging is the modality of choice for the diagnosis and subtype characterization of HCA. Systematic resection of HCA is recommended in male patients owing to the higher incidence of malignant transformation, and surgical excision in women should be reserved for tumors 5 cm or larger associated with an increased risk of complications. Cessation of hormonal therapy and radiologic surveillance in women with HCA tumors smaller than 5 cm shows that the vast majority of HCA remain stable or undergo spontaneous regression. Percutaneous core needle biopsy is of limited value because the therapeutic strategy is based primarily on patient sex and tumor size. Transarterial embolization is the initial treatment for HCA complicated by hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however, frequent sonographic surveillance is recommended.

Use and discontinued use of menopausal hormone therapy by healthy women in Norway

This work aims to study the use of hormone therapy (HT) in a representative cohort of Norwegian women during the menopausal transition, to identify predictors of HT use, and to describe the reappearance of symptoms in former HT users. In 1997, 2,229 women in Hordaland County, aged 40 to 44 years, were selected randomly from a national health survey and followed up with seven postal questionnaires in 1999-2010. Data from 2,002 women (90%) were eligible for analysis. Summary statistics and multiple logistic regression analysis were used. We studied the reappearance of symptoms after HT discontinuation using a subcohort based on their propensity scores for HT use. The 2-year incidence of new HT users dropped from 8.2% (95% CI, 7.0-9.5) in 2002 to 4.3% (95% CI, 3.4-5.2) in 2004 and remained stable despite an increasing prevalence of symptoms in the cohort. Self-rated health was stable during the period. The mean duration of HT use was 4.5 years (95% CI, 4.0-5.0). The odds of HT use were higher among women with daily hot flushes than among those who never or rarely experienced them (odds ratio, 3.2; 95% CI, 2.3-4.4). After HT cessation, hot flushes returned and corresponded to those in untreated controls. The 2-year incidence of HT users decreased almost 50% after 2002. Increasing symptoms and decreasing incidence of HT use did not influence self-rated health. Hot flushes were the strongest predictor of HT use. Symptoms reappeared in most women after HT cessation.

Factors Associated with Successful Discontinuation of Hormone Therapy

Careful management of symptoms, particularly sleep and mood disturbances, may assist women in discontinuing hormone therapy (HT). We sought to describe characteristics associated with successful HT cessation in women who attempted to discontinue estrogen pills/patches with or without progestin. We invited 2,328 women, aged 45-70, enrolled January 1, 2005, to May 31, 2006, at Group Health in Washington State and Harvard Vanguard Medical Associates in Massachusetts, to participate in a telephone survey about HT practices. For the sample, we selected 2,090 women with estrogen dispensings (pharmacy data) during the study period, 200 women without HT dispensing after January 2005, and 240 women with no estrogen dispensings; 1,358 (58.3%) completed the survey. These analyses are based on survey responses. Among 802 women who attempted HT discontinuation, the mean age was 50 years, 93% were postmenopausal, 90% were white, 30% had had a hysterectomy, and 75% experienced hot flashes after discontinuation. Those who did not succeed had greater trouble sleeping (74% vs. 57%) and mood disturbances (51% vs. 34%) than those who succeeded. In multivariable analyses, factors associated with successful discontinuation included doctor advice (odds ratio [OR] 2.62, 95% confidence interval [CI] 1.68-4.08), lack of symptom improvement (OR 4.21, CI 1.50-12.17), vaginal bleeding (OR 5.96, CI 1.44-24.6), and learning to cope with symptoms (OR 3.36, CI 2.21-5.11). Factors associated with unsuccessful HT discontinuation included trouble sleeping (OR 0.40, CI 0.26-0.61) and mood swings or depression (OR 0.63, CI 0.42-0.92). Doctor advice is strongly associated with successful HT discontinuation. Symptom management, particularly sleep and mood disturbances, may help women discontinue HT.

Alcohol consumption and breast cancer risk among postmenopausal women following the cessation of hormone therapy use: the California Teachers Study.

Alcohol consumption increases breast cancer risk, but its effect may be modified by hormone therapy (HT) use, such that exposure to both may be synergistic. Because many women stopped taking HT after mid-2002, it is important to quantify risks associated with alcohol consumption in the context of HT cessation, as these risks may be more relevant to cancer prevention efforts today. Among 40,680 eligible postmenopausal California Teachers Study cohort participants, 660 were diagnosed with invasive breast cancer before 2010. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% confidence intervals (CI). Increased breast cancer risk associated with alcohol consumption was observed among postmenopausal women who were current HT users [RR, 1.60; 95% confidence interval (CI), 1.13-2.26 and RR, 2.11; 95% CI, 1.41-3.15 for <20 and ≥20 g/d of alcohol], with risks being similar by HT preparation. Alcohol did not increase risk among women who had stopped using HT within 3 years or 3 to 4 years before completing the follow-up questionnaire or in the more distant past. Results were similar for estrogen receptor positive (ER+) and ER+PR+ progesterone receptors positive (PR+) tumors; while power was limited, no increase in risk was observed for ER- tumors. Following the cessation of HT use, alcohol consumption is not significantly associated with breast cancer risk, although a nonsignificant increased risk was observed among women who never used HT. Our findings confirm that concurrent exposure to HT and alcohol has a substantial adverse impact on breast cancer risk. However, after HT cessation, this risk is reduced.

Post-myocardial infarction hormone therapy revisited

Current guidelines recommend that postmenopausal hormone therapy should not be used in the setting of secondary prevention of coronary heart disease, and that it should be stopped when an acute coronary event occurs. Reviewing the available data on the issue of discontinuation of therapy in post-myocardial infarction patients shows that the basis for this recommendation is not so solid and clear-cut. In fact, the few relevant studies concluded that cessation of hormone therapy carried no benefit, and perhaps even caused some adverse cardiac events, when compared to women who continued with treatment after they suffered a coronary event. The following article uses a recently published study as an opportunity to review this topic. Based on the literature, my personal view is that long-term hormone users should not automatically withhold therapy post-myocardial infarction, but careful individual evaluation and consideration should precede any decision.

Hip fracture in postmenopausal women after cessation of hormone therapy

Millions of women in the United States and across the globe abruptly discontinued postmenopausal hormone therapy (HT) after the initial Women's Health Initiative trial publication. Few data describing the effects of HT cessation on hip fracture incidence in the general population are available. We evaluated the impact of HT cessation on hip fracture incidence in a large cohort from the Southern California Kaiser Permanente health management organization. In this longitudinal observational study, 80,955 postmenopausal women using HT as of July 2002 were followed up through December 2008. Data on HT use after July 2002, antiosteoporotic medication use, and occurrence of hip fracture were collected from the electronic medical record system. Bone mineral density (BMD) was assessed in 54,209 women once during the study period using the dual-energy x-ray absorptiometry scan. After 6.5 years of follow-up, age- and race-adjusted Cox proportional hazard models showed that women who discontinued HT were at 55% greater risk of hip fracture compared with those who continued using HT (hazard ratio, 1.55; 95% CI, 1.36-1.77). Hip fracture risk increased as early as 2 years after cessation of HT (hazard ratio, 1.52; 95% CI, 1.26-1.84), and the risk incrementally increased with longer duration of cessation (P for trend < 0.0001). Longer duration of HT cessation was linearly correlated with lower BMD (β estimate [SE]) = -0.13 [0.003] T-score SD unit per year of HT cessation; P < 0.0001). Women who discontinued postmenopausal HT had significantly increased risk of hip fracture and lower BMD compared with women who continued taking HT. The protective association of HT with hip fracture disappeared within 2 years of cessation of HT. These results have public health implications with regard to morbidity and mortality from hip fracture.

Predictors of Breast Density Change After Hormone Therapy Cessation: Results from a Randomized Trial

Postmenopausal hormone therapy cessation is associated with a decrease in mammographic density (MD), but it is unknown whether this effect is modified by woman-level characteristics. We investigated whether we could identify characteristics of women who were most likely to experience a decrease in MD due to hormone therapy cessation. Postmenopausal hormone therapy users with a prior screening mammogram (n = 1,168) were randomized to continue hormone therapy or to suspend hormone therapy for 1 month or 2 months before their next screening mammogram. We estimated relative risks (RR) and attributable risks with 95% CIs of a ≥7.5% decrease in percentage MD (%MD) versus no change associated with hormone therapy cessation, stratified by age, body mass index (BMI), parity, and other factors. Hormone therapy cessation increased a woman's likelihood of experiencing a ≥7.5% decrease in %MD by 30% (95% CI = 1.03-1.7), but we found little evidence of effect modification by age, race, BMI, change in BMI, baseline %MD, parity, family history of breast cancer, hormone therapy type, or duration of hormone therapy use. Woman-level factors do not appear to explain why some women experience a decrease in %MD following hormone therapy cessation and others do not. We were unable to identify subgroups of women who are more likely to experience a decrease in MD due to hormone therapy cessation; other factors, such as genetic factors, may be important determinants of hormone therapy-related changes in MD.

Changes in Invasive Breast Cancer and Ductal Carcinoma In Situ Rates in Relation to the Decline in Hormone Therapy Use

To assess trends in invasive breast cancer and ductal carcinoma in situ (DCIS) incidence in association with changes in hormone therapy (HT) use in regular mammography screeners. We included 2,071,814 screening mammography examinations performed between January 1997 and December 2006 on 696,385 women age 40 to 79 years; 9,586 breast cancers were diagnosed within 12 months of a screening examination. We calculated adjusted annual rates (mammogram level) for prevalent HT use, incident invasive breast cancer (overall and by tumor histology and estrogen receptor [ER] status), and incident DCIS. After a precipitous decrease in HT use in 2002, the incidence of invasive breast cancer decreased significantly in 2002 to 2006 among women age 50 to 69 years (P(trend(2002-2006)) = .005) and 70 to 79 years (P(trend(2002-2006)) = .003) but not in women age 40 to 49 years (P(trend(2002-2006)) = .45). DCIS rates significantly decreased in women age 50 to 69 years after 2002 (P(trend(2002-2006)) = .02). Invasive ductal tumors significantly declined in women age 50 to 69 years and 70 to 79 years in 2002 to 2006. In women age 50 to 69 years, invasive lobular and ER-positive cancer rates declined steadily in 2002 to 2005 (P(trend(2002-2005)) = .02 and .03, respectively), but an elevated rate in 2006 rendered the overall trend nonsignificant (P(trend(2002-2006)) = .89 and .91, respectively). In parallel to the sharp decline in HT use in women undergoing regular mammography screening, invasive breast cancer rates decreased in women age 50 to 69 and 70 to 79 years after 2002, and DCIS rates decreased in women age 50 to 69 years, consistent with evidence that HT cessation reduces breast cancer risk. However, the decrease in incidence may have started to level off in 2006; this finding has not been uniformly reported in other populations, warranting further investigation.