Amenorrhea In Premenopausal Women Research Articles

The frequency and predictors of persistent amenorrhea in premenopausal women with colorectal cancer who received adjuvant chemotherapy.

The purpose of this study was to identify the frequency of chemotherapy-induced amenorrhea and associated factors thereof in premenopausal female patients diagnosed with colon cancer. Premenopausal female patients under the age of 50 years who were diagnosed with stages I, II, and III colon cancer were included. A questionnaire surveying personal history including menarche, comorbidities, drugs, other clinical features, and menstrual history during and after completion of chemotherapy was filled by the patients during outpatient visits. Patients who received pelvic radiotherapy were excluded from the study. A total of 60 patients were included in the study. Eleven patients had been treated with surgery alone, and 49 patients had received adjuvant chemotherapy with either fluorouracil (5-FU) alone (n=22) or 5-FU+oxaliplatin (n=27). The frequency of persistent amenorrhea 1 year after receiving chemotherapy was 20% in the whole group, 18% in patients who had received adjuvant chemotherapy with 5-FU alone, and 22% in patients who had received chemotherapy with 5-FU+oxaliplatin. Frequency of persistent amenorrhea was 3.5% in patients under the age of 44 years and 42.8% in patients aged 44 years and older. Multivariate analysis showed that age of 44 years and older (hazard ratio: 29.3; 95% confidence interval: 2.8-309.2, P=0.005) and menarche age of 14 years and older (hazard ratio: 7.6; 95% confidence interval: 1.2-49, P=0.076) were significantly associated with increased risk of persistent amenorrhea. In this study, we found that the frequency of persistent amenorrhea was 20% in patients who received 5-FU monotherapy or oxaliplatin-based adjuvant chemotherapy protocols in colon cancer treatment. Older age and later menarche were the factors that increased the risk of persistent amenorrhea 1 year after chemotherapy.

HIV and amenorrhea: a meta-analysis.

There is conflicting literature to support a link between HIV and amenorrhea. Here, we conduct a meta-analysis to summarize the results from landmark studies in this area and shed light on this important clinical association. Using a search of Ovid Medline and Embase, a total of 322 articles were screened for controlled matched observational studies of amenorrhea in premenopausal women living with HIV (WLWH). For inclusion, amenorrhea was defined as absence of menses for 3 months or longer. The meta-analysis used a random-effects model with an I2 calculated to assess heterogeneity. Six studies from 1996 to 2010 were included in our analysis for a total of 8925 women (6570 WLWH). There was a significant association between HIV status and amenorrhea (OR 1.68, P value 0.0001) without evidence of heterogeneity (I2: 0.0%). In the majority of studies, there was no significant difference in substance use, smoking, or socioeconomic status between WLWH and controls. Additionally, in the majority of studies, amenorrhea in the setting of low BMI was significantly more frequent in WLWH than controls. This meta-analysis provides a large population assessment of amenorrhea in HIV to suggest increased prevalence of menstrual disturbances in WLWH. It lends evidence suggestive that this relation is independent of substance use and socioeconomic status, but may be related to low BMI. Our findings reinforce the importance of routine assessment of reproductive health and time of last menstrual period as part of the health assessment of women, especially those living with HIV.

SLCO1B1*5 polymorphism (rs4149056) is associated with chemotherapy-induced amenorrhea in premenopausal women with breast cancer: a prospective cohort study.

BackgroundBecause inheritance is recognized as playing a role in age at menarche and natural menopause, the development of chemotherapy-induced amenorrhea (CIA) might depend on inherited genetic factors; however, studies that explore such a correlation are few and have received scant attention. Given the importance of this topic we conducted a comprehensive genotype study in young women (≤45 years) with early-stage breast cancer.MethodsOur approach tested the effect of variant polymorphisms in drug metabolism enzymes (DMEs) using a predesigned pharmacogenomics panel (TaqMan® OpenArray®, Life Technologies GmbH, Darmstadt, Germany) in premenopausal women (n = 50). Patients received contemporary chemotherapy; in all cases a cyclophosphamide-based regimen with a dose of at least 500 mg/m2 for six cycles. CIA was considered to be present in women with no resumption of menstrual bleeding within 12 months after completion of chemotherapy or goserelin.ResultsTwenty-six patients (52 %) showed CIA during follow-up whereas 24 women (48 %) remained premenopausal. Of all the DMEs studied, only the SLCO1B1*5 (rs4149056) genotype was associated with the development of CIA (P = 0.017). Of the 26 patients who were homozygous for the T/T allele SLCO1B1*5, 18 (69.2 %) developed CIA compared with 8 (30.8 %) of the 22 patients who were heterozygous (C/T allele). The association of heterozygous SLCO1B1*5 allele (OR 0.038; 95%CI: 0.05–0.92) with a lower risk of developing CIA remained significant in a binary logistic regression analysis that include age, SLCO1B1*5 allele variants, and goserelin therapy.ConclusionsPatient age and SLCO1B1*5 allele variants predict the likelihood of young women with breast cancer developing CIA.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2373-3) contains supplementary material, which is available to authorized users.

Incidence of Chemotherapy- and Chemoradiotherapy-Induced Amenorrhea in Premenopausal Women With Stage II/III Colorectal Cancer

BackgroundThe incidence rates of colorectal cancer (CRC) in young individuals are increasing. There has been a significant improvement in overall survival in CRC because of advances in adjuvant chemotherapy and chemoradiotherapy over the past decades. However, these procedures may compromise the function of the reproductive system, and ovarian failure and premature menopause may occur. The objective of this analysis was to determine the incidence of long-term amenorrhea (≥ 12 months) in women with CRC aged 40 years and younger after adjuvant treatment. Patients and MethodsThe authors identified 162 premenopausal women with CRC aged 40 years or younger who were treated with adjuvant chemotherapy and chemoradiotherapy at Fudan University Shanghai Cancer Center from January 2008 to December 2012. One hundred twenty-three patients met all eligibility criteria and had sufficient follow-up for evaluation. The median age at diagnosis in patients with colon and rectal cancers was, respectively, 36 and 35 years (range, 17-40 and 24-40 years). ResultsAll patients had regular menses before treatment; 3 patients with colon cancer (4.2%) experienced long-term amenorrhea, and 48 patients with rectal cancer (94.1%) experienced long-term amenorrhea. The incidence of amenorrhea was significantly lower in patients with colon cancer (4.2%; 3 of 72) than in patients with rectal cancer (94.1%; 48 of 51) (P < .01). ConclusionIn this retrospective series, the incidence of amenorrhea in patients with colon and rectal cancers was 4.2% and 94.1%, respectively. We believe our data support the fact that young female patients with CRC, especially those with rectal cancer who are scheduled to undergo pelvic irradiation, should be counseled regarding fertility preservation options, including ovarian transposition and cryopreservation of ovarian tissue, embryo, or oocyte.

Biomarker prediction of chemotherapy-related amenorrhea in premenopausal women with breast cancer participating in E5103

This study aimed to investigate whether pre-chemotherapy anti-mullerian hormone (AMH) is a biomarker for chemotherapy-related amenorrhea (CRA) in breast cancer patients. A multicenter randomized controlled trial, ECOG5103, assigned patients with early stage breast cancer to standard doxorubicin-cyclophosphamide followed by paclitaxel with either placebo or one of two durations of bevacizumab therapy. Five hundred ninety-one patients were part of the decision-making/quality of life substudy, in which there were surveys from baseline through 18-month follow-up. One hundred twenty-four women were included in this analysis of menses data because they were premenopausal at enrollment, responded to the 12-month survey, had not undergone bilateral oophorectomy or ovarian function suppression before that survey, and had serum banked for research before chemotherapy. One hundred of the 124 also responded to the 18-month survey. Median age was 45 years (range 25-55), and median serum AMH level was 0.11 ng/mL (range 0.01-8.63) prior to treatment. Eighty-two percent had CRA at 12 months, and 81 % at 18 months. In multivariate analyses, older age (p = 0.0003) was the only statistically significant predictor of 12-month CRA, but at 18-months, lower pre-chemotherapy AMH (p = 0.04) and older age (p = 0.008) were both statistically significant predictors of CRA. Race, bevacizumab therapy, and tamoxifen use were not statistically significantly associated with CRA after adjustment for AMH and age. Pre-chemotherapy AMH level is a potential novel biomarker for CRA in premenopausal women with early stage breast cancer. Further research to evaluate the clinical utility of AMH testing is warranted.

Incidence of Chemotherapy-Induced Amenorrhea in Premenopausal Women Treated With Adjuvant FOLFOX for Colorectal Cancer

BackgroundStudies indicate that the incidence of young women diagnosed with colorectal cancer is rising, thus there is an increasing number of female colorectal cancer survivors of premenopausal and child-bearing age. Adjuvant FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) chemotherapy is the most widely used standard treatment for stage III and high-risk stage II colon cancer. We evaluated the incidence of FOLFOX-induced amenorrhea in women age 50 and younger treated with adjuvant therapy for colorectal cancer. Patients and MethodsA search of pharmacy records identified 119 women age 50 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2011. Eligible patients were mailed an anonymous questionnaire. The returned surveys were reviewed and the results tallied. ResultsSeventy-three patients returned the questionnaire. Twenty-four patients were excluded from analysis: 19 were treated with pelvic radiotherapy, 2 patients had undergone bilateral oophorectomy, 2 had a hysterectomy, and 1 stopped menstruating before diagnosis. Forty-nine patient responses were analyzed. In total, 41% (n = 20) experienced amenorrhea during chemotherapy. Sixteen percent had persistent amenorrhea 1 year after completion of chemotherapy. The incidence of amenorrhea during chemotherapy trended higher in patients aged older than 40 compared with patients aged 40 and younger (59% vs. 31% [P = .075]). There was no statistically significant difference in persistent amenorrhea between the 2 age groups (24% vs. 13%; P = .42). ConclusionIn this retrospective series, there appears to be a trend toward FOLFOX induced amenorrhea during chemotherapy increasing with age. Twenty-four percent of women older than the age of 40 were found to have persistent amenorrhea after FOLFOX therapy. Because of the small sample size, the study is underpowered to detect a statistically significant difference between older and younger patients. Prospective studies are planned to further characterize the effect of FOLFOX on early menopause and fertility.

PO56 Prevalence of early menopause/secondary amenorrhea in premenopausal women diagnosed with early breast cancer who received adjuvant or neoadjuvant treatment based on docetaxel

undergoing BCT in the Indian scenario hypothesizing that for carefully selected patients BCT is a viable treatment option. Methods: In a retrospective review of prospectively maintained computerized database of 2500 operated breast cancer patients a total of 355 patients undergoing BCT were identified. Patients with age less than 40 years at presentation, unilateral lesion and known receptor and Her 2 status were included. Patients who received NACT and who did not complete planned RT were excluded. Results: 136 patients under 40 years of age had BCT. These patients were divided into TNBC and Non TNBC groups. TNBC patients constituted 54% of patients. Mean age (34.7 vs 35.1), tumour size (3.1 vs 2.6), stage at presentation (Stage I 15% vs 20%, Stage II 65% vs 75%, Stage III 20% vs 5%), pathological nodal status (pN0 53% vs 62%) and average LN dissected (11.5 vs 12.5) were comparable in the two groups. Standard lumpectomy was offered to all patients whereas Quadrantectomy (14% vs 6%) and Oncoplasty with volume replacement (4 patients vs. 2 patients) was used in both groups. At a mean follow up of 36 months Loco regional recurrence was 2.74% vs. 1.6% and Distant metastasis 6.8% vs. 11.1% in TNBC and non-TNBC group respectively. Discussion: Results of the present study indicate feasibility and safety of BCT in young TNBC patients. Hence young age at presentation associated with TNBC is not a contraindication for BCT provided they fulfill the standard criteria for BCT.

Incidence of chemotherapy-induced amenorrhea in premenopausal women treated with adjuvant FOLFOX for colorectal cancer.

e14112 Background: The gonadotoxicity of oxaliplatin-based chemotherapy is largely unknown. Studies indicate that the incidence of young women diagnosed with colorectal cancer is rising, thus there is an increasing number of female colorectal cancer (crc) survivors of premenopausal and child-bearing age. Adjuvant FOLFOX chemotherapy is the most widely used standard treatment for stage III and high-risk stage II colon cancer. The objective of this analysis was to evaluate the incidence of FOLFOX induced amenorrhea in women age 50 or younger treated with adjuvant therapy for colorectal cancer. Methods: A search of computerized pharmacy records identified 119 women age 50 or younger who received adjuvant FOLFOX chemotherapy at Memorial Sloan-Kettering for stage II or III colorectal cancer from January 2002 and January 2011 . Eligible patients were mailed an anonymous questionnaire. The returned surveys were reviewed and the results tallied. Results: Seventy three patients returned the questionnaire. Twenty four patients were excluded from analysis; 19 were treated with radiotherapy, 1 patient had undergone bilateral oophorectomy, 1 had a hysterectomy and 3 stopped menstruating prior to diagnosis. Forty nine patients were analyzed. In total, 41% experienced amenorrhea during chemotherapy. Sixteen percent had persistent amenorrhea approximately one year after completion of chemotherapy. The incidence of amenorrhea during chemotherapy and persistent amenorrhea was higher in patients age 40 or older than in patients under 40 (59% vs 31% (p=.17) and 24% vs 13% (p=.33), respectively). Conclusions: In this retrospective study, it appears that the incidence of FOLFOX chemotherapy induced amenorrhea is increased with age. Due to the small sample size the study may be underpowered to detect a statistical difference. Prospective studies are planned to more accurately characterize the impact of FOLFOX on early menopause and fertility.

Efficacy and safety of ovarian stimulation before chemotherapy in 205 cases

Ovarian stimulation and cryopreservation of fertilized oocytes before cancer therapy is the best established and efficient fertility preservation technique and should still be considered before chemotherapy. Within a short time frame of 2 weeks, between 8.6 (18-25 y) and 5.1 (36-40 y) fertilized oocytes can be cryopreserved.

The effects of paclitaxel, dose density, and trastuzumab on treatment‐related amenorrhea in premenopausal women with breast cancer

Little information is available regarding the effects of new adjuvant treatment regimens on menstrual functioning in premenopausal women with early breast cancer. The authors conducted a retrospective review of data from premenopausal women who received treatment for early breast cancer to evaluate the rates of amenorrhea in follow-up. The women who were included received treatment with either doxorubicin and cyclophosphamide (AC) or combined AC and paclitaxel (T) (AC-T) given either every 3 weeks, or as a dose-dense (DD) regimen, or as AC followed by weekly T with trastuzumab or followed by trastuzumab (AC-T+trastuzumab). A multivariate logistic regression analysis was conducted to evaluate amenorrhea during follow-up. Of 431 patients who were eligible for analysis, the average age at diagnosis was 13 years (range, 25-55 years), 61% of women received AC only, and 39% received AC-T. Of the 39% who received AC-T, 49% of women received DD therapy, 14% received AC-T+trastuzumab, and 71% of all patients received tamoxifen (TAM). The median follow-up was 33 months (range, 6-114 months). After adjusting for age, weight, gravidity, parity, age at menarche, smoking, alcohol use, TAM use, type and regimen of chemotherapy, and use of trastuzumab, the likelihood of remaining amenorrheic was not statistically different in patients who received AC-T versus AC (odds ratio [OR], 1.59; 95% confidence interval [CI], 0.8-3.2), DD treatment versus treatment every 3 weeks (OR, 0.56; 95% CI, 0.25-1.3), or AC-T + trastuzumab (OR, 0.6; 95% CI, 0.22-1.61). Amenorrhea was associated significantly with TAM use and age at diagnosis. Recent advances in the adjuvant treatment of early breast cancer do not appear to have increased the risk of amenorrhea in premenopausal women.

NSABP B-30: definitive analysis of patient outcome from a randomized trial evaluating different schedules and combinations of adjuvant therapy containing doxorubicin, docetaxel and cyclophosphamide in women with operable, node-positive breast cancer.

Abstract Abstract #75 Background: The primary aims of this study were to determine 1) if a concurrent regimen of therapy containing cyclophosphamide compared to a sequential regimen containing cyclophosphamide would prolong disease-free survival (DFS) and overall survival (OS) and 2) if a regimen without cyclophosphamide was at least as efficacious as the two regimens containing cyclophosphamide. The secondary aims were to compare toxicities among the three regimens and to compare differences in amenorrhea in premenopausal women in each arm and its relationship to outcome.&amp;#x2028; Materials and Methods: 5351 pts with cT1-3, N0-1, M0 were enrolled from 3/1/99 to 3/31/2004. 1783 pts were randomized to Group 1 [doxorubicin (A) 60 mg/m2 and C 600 mg/m2 q 3 weeks (wks) x 4 followed by docetaxel (T) 100 mg/m2 q 3 wks x 4], 1784 pts to Group 2 [A 50 mg/m2 and T 75 mg/m2 q 3 wks x 4], and 1784 to Group 3 [A 50 mg/m2 T 75 mg/m2 and cyclophosphamide (C) 500 mg/m2 q 3 wks x 4]. All patients with ER-positive tumors received hormonal therapy after completing chemotherapy. The protocol specifies that 800 deaths are required for the definitive analysis. This is expected to occur by Fall 2008.&amp;#x2028; Results: Mean time on study is currently 79 months. At entry, 46% of pts were &amp;lt; 49 yrs; 54% were &amp;gt; 50 yrs. 82% were white, 10% black, 4% Hispanic. 66% had 1-3 positive nodes, 26% had 4-9, and 8% had 10+. 75% of pts were ER pos. 49% had lumpectomy, 51% mastectomy, and 24% local/regional radiotherapy. Mean tumor size was 2.5 cm. The presentation will include the first results of DFS, OS, and relevant toxicities from the trial. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 75.

Chemotherapy-related amenorrhea in premenopausalwomen with breast cancer

To report the incidence of chemotherapy-related amenorrhea (CRA) from chemotherapy with/without adjuvant endocrine therapy in premenopausal women with breast cancer and to analyze the related factors. From January 2000 to August 2006, 326 premenopausal women (<or=50 y old) who completed chemotherapy were available for analysis. The CRA definitional criterion in this study was no menstruation for 6 months in a woman who was premenopausal at diagnosis. As risk factors for CRA, woman's age, the type of chemotherapy regimen, adjuvant endocrine therapy use, and body mass index were evaluated. The median age was 42 years (range, 22-50 y). The median follow-up period was 37 months (range, 12-80 mo). Women were divided into two groups by age at diagnosis: 128 women in group 1 (less than 40 years old) and 198 women in group 2 (age >or=40 y). CRA occurred in a total of 223 (68%) women: 43% in group 1 and 85% in group 2 (P < 0.001). Despite CRA, 14% resumed menstruation: 24% in group 1 and 11% in group 2. Another 40 (12%) women had less than 6 months of menstruation interruption. Permanent CRA was related with age at diagnosis and use of adjuvant endocrine therapy (P < 0.05). In this study, there were four pregnancies, two of which resulted in therapeutic abortion due to ongoing chemotherapy. This study confirmed that the rate of CRA depends on age at diagnosis and the use of adjuvant endocrine therapy. It is essential to inform young women of reproductive age of the possibility of amenorrhea or resumption of menstruation and contraceptive options.

Amenorrhea in premenopausal women on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm of NSABP B-30 trial

The NSABP B-30 trial addresses whether amenorrhea after adjuvant chemotherapy increases survival. Preliminary to the trial outcome analysis, we examined the incidence of amenorrhea and its relationship to symptoms and quality of life (QOL) in the standard-care arm of this adjuvant breast cancer trial. Premenopausal women treated on the doxorubicin-and-cyclophosphamide-followed-by-docetaxel arm were included. Questionnaires assessing menstrual history, QOL, and symptoms were administered at baseline, day 1 of cycle 4 (or 9 weeks from start of chemotherapy for those who stopped chemotherapy early), and at 6, 12, and 24 months. Seven hundred and eight patients were evaluable for the analysis, with median potential follow-up of 57.5 months. Of these, 321 patients also participated in the QOL substudy. Of the 708 patients, 83% reported > or =1 episode of amenorrhea for > or =6 months. The estimated rate of resumption of menses at 24 months was 45.3% for women <40 years, 10.9% for women 40-50, and 3.2% for women >50 years. Those treated with tamoxifen were more likely to become amenorrheic (p = 0.003). Menstrual status was not significantly associated with QOL or symptoms. Prolonged amenorrhea is associated with a regimen that contains doxorubicin, cyclophosphamide, and docetaxel, and is age dependent and impacted by tamoxifen use. Vasomotor symptoms are common in this patient population but are not associated with menstrual status. These results can be used to inform premenopausal women about the risk and time course of amenorrhea associated with this common adjuvant therapy regimen, along with the effects on symptoms and QOL.

Amenorrhea in Premenopausal Women After Adjuvant Chemotherapy for Breast Cancer

Chemotherapy and ovarian ablation both independently improve survival in premenopausal women with hormone-sensitive breast cancer. Amenorrhea is a well-recognized occurrence after chemotherapy. The rate of chemotherapy-induced amenorrhea varies with patient age and chemotherapy regimens administered. However, the impact of chemotherapy-induced amenorrhea on prognosis is still being defined. Older studies in premenopausal women argue that the benefit with chemotherapy is a result of direct cytotoxicity alone. However, studies that restrict outcome analysis to hormone receptor-positive tumors suggest that chemotherapy has a dual mechanism in women with hormone-responsive tumors; indirect endocrine manipulation secondary to chemotherapy-induced ovarian suppression and direct cytotoxicity. The significant health ramifications involved with the induction of premature menopause as well as potential benefits necessitate a comprehensive evaluation of chemotherapy-induced amenorrhea. This review will discuss the incidence of amenorrhea with commonly-used adjuvant chemotherapeutic regimens, the possible benefits of chemotherapy-induced amenorrhea, and the challenges of interpreting the existing data in breast cancer trials.

P-166: Chemotherapy-related amenorrhea in premenopausal women with breast cancer: The effect of paclitaxel, dose density and trastuzumab

The effect of the addition of paclitaxel (T) to adriamycin and cyclophosphamide (AC), use of a dose dense (DD, q2wk) regimen, or use of trastuzumab/herceptin (H) on menstrual functioning in premenopausal women with early breast cancer remains uncertain. No previous studies have evaluated the effects of DD and H on the menstrual cycle.

Amenorrhea in premenopausal women on the doxorubicin (A) and cyclophosphamide (C) → docetaxel (T) arm of NSABP B-30: Preliminary results

537 Background: NSABP B-30, an adjuvant study with 3 chemotherapy treatment arms in node-positive breast cancer, accrued 5351 patients (pts) from 1999–2004. A secondary objective of this study was to document menstrual history (MH) in premenopausal women in each treatment arm and its relationship to symptoms, quality of life (QOL), disease-free survival, and survival. This report describes preliminary results re MH in the AC ⋄ T arm. Methods: Pts completed a baseline and MH follow-up form day 1 cycle 4 (D1C4), and 6, 12, 18, 24 months (mo) after randomization. Pts < 60 yrs who had been on study ≥ 24 mo were included in this analysis. Results: Of the 528 pts with 24-mo follow-up in the MH study, 490 pts (93%) were menstruating regularly at start of chemotherapy, with 17% of these pts amenorrheic for ≥ 3 mo by D1C4. Including full length of follow-up, 80% reported amenorrhea ≥ 6 mo, 11% for ≥ 3 mo, 4% changes in menstrual cycles, and 5% no changes. The table provides rates of amenorrhea at 6- and 12-month follow-up by age and tamoxifen usage. In a sensitivity analysis designed to account for missing data, median duration of amenorrhea for pts ≤ 30 yrs was estimated to be 3–13 mo; 30.1–40 yrs 9–17 mo; 40.1–60 yrs >24 mo. 354 pts participated in both QOL and MH studies. Menstrual status was not a significant predictor of the FACT-B Trial Outcome Index in repeated measures analysis (p=0.35). Conclusions: Amenorrhea occurred in a substantial percent of women after AC⋄ T, which increased with age. There was no correlation with QOL in this early analysis. Future studies include time to amenorrhea and examine the association of amenorrhea with body mass index and race. No significant financial relationships to disclose.

Chemoendokrine Therapie des Mammakarzinoms bei prämenopausalen Patientinnen

Ovarian ablation has been used for a long period of time as an effective method in breast cancer treatment. The effectiveness of this therapy has been proven by multiple trials which by now provide long-time results. Currently available endocrine therapies either lower estrogen production or modulate estrogen receptor (ER) activity or regulate the expression of the ER. The efficacy of chemotherapy is partly related to the induction of secondary amenorrhea in premenopausal women by cytotoxic agents. A comparison of current standard chemotherapies with endocrine therapies shows that ovarian suppression and chemotherapy are equieffective in premenopausal women with hormone-sensitive breast cancer. Ovarian ablation increases long-lasting survival in breast cancer patients younger than 50 years of age, at least in the absence of chemotherapy. In premenopausal women with hormone-sensitive breast cancer ovarian suppression with gosereline with or without tamoxifen seems to be at least as effective as CMF chemotherapy alone. There are data which indicate a superiority of gosereline plus tamoxifen to gosereline monotherapy, at least if chemotherapy has been applied as well. Sequential use of gosereline after CMF chemotherapy seems to be superior to any modality alone in node-negative patients, at least in women younger than 40 years of age with hormone-sensitive tumors. Monochemotherapy alone is not sufficient in patients younger than 35 years of age with hormone-sensitive tumors. On the basis of the available data a final answer to the use of combined chemoendocrine therapy cannot be given as yet.

Chemoendokrine Therapie des Mammakarzinoms bei prämenopausalen Patientinnen

Im Rahmen der adjuvanten endokrinen Therapie des prämenopausalen Mammakarzinoms besitzt die ovarielle Ablation eine besondere Bedeutung. Die Wirksamkeit dieser Therapieform wurde in etlichen Studien belegt, zu denen mittlerweile auch Langzeitergebnisse vorliegen. Derzeit verfügbare endokrine Therapien senken entweder die Östrogenproduktion oder modulieren die Aktivität des Östrogenrezeptors (ER) bzw. regulieren die Expression des ER. Die Wirksamkeit von Chemotherapien bei prämenopausalen Patientinnen wird unter anderem auf die Induktion einer sekundären Amenorrhö zurückgeführt. Der Vergleich von Standardchemotherapien mit endokrinen Therapieformen zeigt, dass die ovarielle Suppression bei prämenopausalen Patientinnen mit hormonsensiblem Mammakarzinom einer Chemotherapie gleichwertig ist. Die ovarielle Ablation verbessert das Langzeitüberleben von Patientinnen unter 50 Jahren, zumindest in Abwesenheit einer Chemotherapie. Bei prämenopausalen Patientinnen mit hormonsensiblem Mammakarzinom scheint die ovarielle Suppression mit Goserelin mit oder ohne Tamoxifen äquieffektiv zu sein zur Chemotherapie mit CMF. Es gibt Hinweise, dass Goserelin plus Tamoxifen effektiver ist als eine Goserelin-Monotherapie, zumindest wenn auch eine Chemotherapie durchgeführt wurde. Der sequenzielle Einsatz von Goserelin nach CMF scheint besser als die jeweilige Monotherapie bei Patientinnen mit nodalnegativem Mammakarzinom; dies gilt zumindest für Patientinnen unter 40 Jahren mit hormonsensiblem Tumor. Die alleinige Chemotherapie bei Patientinnen unter 35 Jahren mit hormonsensiblem Mammakarzinom ist nicht ausreichend. Eine eindeutige Aussage zum kombinierten Einsatz von Chemotherapie und endokriner Therapie kann zum jetzigen Zeitpunkt jedoch aufgrund der angeführten Datenlage abschließend nicht gegeben werden (Tab. [1]).

Oral pilocarpine to treat vaginal xerosis associated with chemotherapy-induced amenorrhea in pre-menopausal women

8099 Background: Chemotherapy-induced amenorrhea frequently results in side effects common to those experienced in menopause; vaginal dryness (VD) and its related symptoms are prominent examples. Although many of these side effects respond to the use of estrogen replacement therapy (ERT), many cancer survivors choose to not chance the risks linked with ERT. Previous results in a placebo-controlled Phase III study treating xeroses associated with Sjögren's syndrome with oral pilocarpine (OP){Salagen® Tablets}demonstrated impressive improvement in VD, P≤0.02 (25% vs.14%):Vivino et al; Arch Intern Med. 1999;159. Methods: A 12-week, open-label pilot study was conducted using OP (5mg./qid) in pre-menopausal women with VD caused by the effects of high cumulative dose cyclophosphamide on ovarian function. Study enrollment required a minimum 2 month history of VD and 4 months status-post chemotherapy. The primary endpoint of this study was a global assessment of VD measured on a standard visual analog scale (VAS), at 6 and 12 weeks of treatment, or at final study visit if prior to week 12. Participants were asked to characterize their VD at these visits compared to their VD before treatment with OP; each participant acted as her own control. Results: The pre-study expectation was for a 25 mm (absolute) improvement in the participants' VAS by end of study. Four of four evaluable participants treated with OP experienced a marked clinical improvement in VD.Three responders recorded ≥40mm absolute gain in VAS, the fourth gained ≥28mm. Conclusions: OP, a well-tolerated muscarinic agonist was able to stimulate remaining mucus and other moisture producing cells in the vaginal mucosa & muscularis to the extent that a marked clinical improvement in VD was experienced by each of the study participants. The only AEs experienced were mild and of the known side effects of OP and did not interfere with treatment. These results warrant further investigation as a possible treatment for symptomatic relief of this difficult problem. No significant financial relationships to disclose.

Oral pilocarpine to treat vaginal xerosis associated with chemotherapy-induced amenorrhea in pre-menopausal women

Oral pilocarpine to treat vaginal xerosis associated with chemotherapy-induced amenorrhea in pre-menopausal women