Therapy In Premenopausal Women Research Articles

Reinstatement of Serum Pregnanolone Isomers and Progesterone During Alcohol Detoxification Therapy in Premenopausal Women

Alcohol abuse is associated with menstrual irregularities related to the inhibition of progesterone secretion involved in regulation of the menstrual cycle. Reduced progesterone metabolites, including pregnanolone isomers (PIs), are efficient neuromodulators. The authors attempted to evaluate whether levels of PIs reflect impairment in progesterone biosynthesis in premenopausal women treated for alcohol addiction and whether alcohol detoxification therapy contributes to the restoration of their reproductive functions and psychosomatic stability by influencing steroid biosynthesis. Serum allopregnanolone (3alpha-hydroxy-5alpha-pregnan-20-one; P3alpha5alpha), pregnanolone (P3alpha5beta), isopregnanolone (P3beta5alpha), epipregnanolone (P3beta5beta), progesterone, pregnanolone sulfate (PregS), pregnanolone, and estradiol were measured in 20 women during therapy (at start, three days, 14 days, one month, and four months) by gas chromatography-mass spectrometry or radioimmunoassay. The results were evaluated by a linear mixed model for longitudinal data, with stage of the treatment and subject as categorical factors, phase of the menstrual cycle as a time-varying covariate, and age of the subject as a covariate and by regression in individual stages of the menstrual cycle. During detoxification treatment, progesterone increased in the luteal phase. P3alpha5alpha, P3beta5alpha, and P3beta5beta rose in both phases of the menstrual cycle. Given the similar mechanism in the effects of alcohol and steroids in activating gamma-aminobutyric acid A receptors, the restoration of progesterone and PIs during therapy could be explained by an adaptation to increasing requests for gamma-aminobutyric acid A-receptor activating substances owing to the cessation of alcohol intake or by the regeneration of progesterone formation. In conclusion, the reinstatement of progesterone, P3alpha5alpha, and P3beta5beta serum levels demonstrates the favorable effect of detoxification therapy on both reproductive functions and the psychosomatic stability of premenopausal women treated for alcohol addiction.

Endocrinology and hormone therapy in breast cancer: endocrine therapy in premenopausal women.

Endocrine therapy remains important in premenopausal women with hormone receptor positive breast cancer. Ovarian ablation, used alone, is effective in delaying recurrence and increasing survival in such women. When added to chemotherapy, it is less clear that it is effective perhaps because of the endocrine ablative effect of chemotherapy. Trials comparing ovarian ablation with or without tamoxifen to CMF-type chemotherapy suggest that the endocrine therapy is equivalent to or better than this chemotherapy in women whose tumors have estrogen and/or progesterone receptor. Tamoxifen is also effective in preventing recurrence and prolonging survival in the adjuvant setting in premenopausal women. While most of the available data deals with tamoxifen given alone, it appears to have a similar beneficial effect when added to chemotherapy in the premenopausal adjuvant setting. Adjuvant aromatase inhibitors should not be used in premenopausal women.

Introducing Breast Cancer Research's updates on clinical trials

In the present issue of Breast Cancer Research, we are launching a new feature focused on clinical research in breast cancer. Each issue will contain an update from one of the major worldwide groups that focuses on their most important clinical trials. The objectives and scientific rationale for the trial(s) will be described, and the status of the trial(s) (present accrual, planned closure date) will also be provided. We are pleased that the European Organisation for Research and Treatment of Cancer (Belgium) was willing to be the first in this series. We have two goals in mind in promoting this new feature. First, we want to provide a forum for each of the cooperative groups to share their current research. In this way, clinicians and researchers around the world can become familiar with the questions that are being addressed in ongoing trials. These updates may, in some cases, lead to collaborations across groups. The recent and ongoing experience with the trials in premenopausal women with hormone receptor-positive tumors has demonstrated the feasibility of conducting clinical trials (SOFT, A Phase III Trial Evaluating the Role of Ovarian Function Suppression and the Role of Exemestane as Adjuvant Therapies for Premenopausal Women with Endocrine Responsive Breast Cancer; TEXT, A Phase III Trial Evaluating the Role of Exemestane Plus GnRH Analogue as Adjuvant Therapy for Premenopausal Women with Endocrine Responsive Breast Cancer; and PERCHE, A Phase III Trial Evaluating the Role of Chemotherapy as Adjuvant Therapy for Premenopausal Women with Endocrine Responsive Breast Cancer Who Receive Endocrine Therapy) on both sides of the Atlantic Ocean. Furthermore, we hope these clinical trial updates may lead to enhanced patient accrual through awareness and referrals. The second goal is even more important. Despite improvements in breast cancer screening, local therapy, and adjuvant systemic therapy, far too many women ultimately die from breast cancer. Over the past decade, there has been an unprecedented expansion in our understanding of the basic mechanisms underlying breast cancer. There is greater knowledge than ever before about growth factor receptors, signaling pathways, tumor–stromal interactions, and a whole range of other topics that could lead to therapeutic advances. It is our view that a substantial reduction in breast cancer mortality is critically dependent on close collaborations between basic, translational, and clinical researchers. By publishing updates of the ongoing trials, we hope to bring basic and translational scientists who work on breast cancer closer to the clinic by exposing them to the unanswered clinical questions. At the same time, we challenge clinicians and clinical trialists to interact with their colleagues in the laboratory and to design trials that will help answer questions that arise from laboratory-based hypotheses. At some point in the not so distant future, mortality from breast cancer will be a concept of the past. But approaching this goal in the next decade will depend upon close and thoughtful collaborations between those of us who see patients and design trials, and our colleagues who are working in the laboratory. We hope the series will be of interest to the readership of Breast Cancer Research. Over the months ahead, we welcome and look forward to your comments on how we can improve this effort.

Combined use of goserelin (zoladex) and anastrozole (arimidex) as second-line endocrine therapy in premenopausal women with advanced breast cancer — a study of its clinical and endocrine effects

Combined use of goserelin (zoladex) and anastrozole (arimidex) as second-line endocrine therapy in premenopausal women with advanced breast cancer — a study of its clinical and endocrine effects

Resting ECG is modified after oophorectomy and regresses with estrogen replacement therapy in premenopausal women

Objective: To assess the effects of bilateral oophorectomy on the resting ECG and whether they regress with estrogen replacement therapy. Study design: Twenty-six premenopausal and 15 postmenopausal women were enrolled in the present study. All women had undergone hysterectomy and bilateral ovariectomy. All women underwent 12-lead ECG on admission to hospital. A second ECG was recorded 20–25 days after surgery. After this second ECG, premenopausal women were randomly divided into two groups. The women of Group A ( n=14) received transdermal ethinyl estradiol (EE). The women of Group B ( n=12) did not receive any therapy. A third ECG was performed in both groups 30–35 days after randomization. Results: Bilateral oophorectomy did not induce any significant modifications in the ECG parameters of the postmenopausal women whereas in the premenopausal women, we observed a significant increment in mean duration of the T wave, a significant decrease in its amplitude and significant reduction in ST depression in V2, V3, V4 and V5. The third ECG showed regression of the ECG modifications in Group A. In the women of Group B, the second and third ECGs were not substantially different, but there were statistically significant differences between the first and third ECGs. Conclusions: The results of the present study show that ovariectomy induces significant though not clinically evident modifications in resting ECG. These ECG changes are probably due to the sudden reduction in sex hormone plasma levels after ovariectomy. Administration of estradiol induced regression of the ECG modifications.

The role of hormone replacement therapy in women with a current or past history of endometriosis

Endometriosis is an oestrogen sensitive condition, leading to reluctance to prescribe hormone replacement therapy. Treatment of endometriosis either medically with gonadotrophin releasing hormone analogues or with surgery involving bilateral oophorectomy leads to oestrogen deficiency. While this may lead to vasomotor symptoms, the consequence which has been of most concern is a reduction in bone mass. Repeated courses of gonadotrophin releasing hormone analogues may mean that women with endometriosis enter the menopause with a below average bone density. Thus, there is a place for hormone replacement therapy both as add-back therapy in premenopausal women receiving gonadotrophin releasing hormone analogues, and in postmenopausal women with a past history of endometriosis. Addback therapy with continuous combined regimes and tibolone do not prevent disease resolution in the hypogonadal patient. The evidence regarding the use of hormone replacement therapy in patients with a history of endometriosis is poor, but suggests that we could be less conservative than we have been.

P276 Clinical results of EP and P therapy in premenopausal women

P276 Clinical results of EP and P therapy in premenopausal women

Ovarian torsion in a premenopausal woman treated with tamoxifen for breast cancer

Tamoxifen therapy in premenopausal women with breast cancer may be associated with the development of ovarian cysts. In this report, a case of ovarian torsion associated with TAM therapy is described.

Assessing the cost effectiveness of adjuvant therapies in early breast cancer using a decision analysis model

We have developed a decision analysis model that uses the results of available randomized controlled trials to model the natural history of early breast cancer and assess the potential clinical and financial effects of using adjuvant therapies. The original model was used to assess the impact of chemotherapy in hypothetical groups of 45-year-old and 60-year-old node-negative, estrogen receptor-negative women. Using the 1992 Early Breast Cancer Trialists' Collaborative Group report, we have expanded and revised the model to assess: 1) the role of tamoxifen alone, chemotherapy alone, or combined therapy in pre-menopausal women, and 2) chemotherapy in elderly women with node-negative, estrogen receptor-negative cancer. For pre-menopausal women, we found that chemotherapy increases quality adjusted life expectancy and survival by a substantial amount at a cost less than most accepted medical interventions. Combined therapy is beneficial and cost-effective in estrogen receptor-positive cancer. For the elderly, chemotherapy prolongs survival but to a lesser extent compared to younger women. The cost of this benefit is high but within the range of commonly reimbursed procedures for women under age 75 without other co-existing conditions. For most patients some form of adjuvant therapy is beneficial and cost-effective. The model builds upon the data derived from collaborative efforts assessing the effectiveness of adjuvant therapies. The model highlights the need for an equal commitment to assessing the economic and quality of life impacts of breast cancer treatments.

Longitudinal study of bone loss after thyroidectomy and suppressive thyroxine therapy in premenopausal women.

The effects of suppressive doses of L-thyroxine on the appendicular and axial bone mineral content were followed for 12-36 months after total or subtotal thyroidectomy in 15 premenopausal women. Compared to age-matched controls, these patients had a more marked bone loss of the spinal bone mineral content (2.6 +/- 1.9% vs 0.2 +/- 1.2% per year). The changes in radial cortical bone density were not significantly different from the control group. We conclude that when a suppressive therapy with L-thyroxine is necessary the rate of bone loss should be monitored at regular intervals.

Therapy in Premenopausal Women with Advanced, Oestrogen Positive or/and Progesterone Positive Breast Cancer: Surgical Oophorectomy versus the LHRH Analogue, Zoladex

The basis and design of a trial that will compare surgical oophorectomy with the LHRH analogue, Zoladex, in the treatment of premenopausal women with advanced, oestrogen receptor-positive or progesterone receptor-positive breast cancer, is described.

Endocrine therapy of breast cancer. Status and perspectives

The modified therapeutic approach to metastatic breast cancer has been influenced by the realization that it cannot be cured even with the most aggressive chemotherapy. Consequently, quality of life and duration of remission have become more important parameters than judging therapeutic success only by rate of remission. The discovery of hormone receptors and of potent drugs with few side effects, which replaced ablative procedures, has led to an increased significance of endocrine therapy. Improved understanding of the endocrine mechanisms regulating malignant growth and their relationship to growth factors and tumor associated proteolysis have concurrently stimulated clinical research. Endocrine manipulation of malignant growth is based on competitive (antihormones), inhibitive (aromatase inhibitors, LHRH agonists), additive (gestagens) and ablative (ovarectomy) mechanisms. The knowledge of the optimal sequence and modality is mandatory for an individualized treatment, leading to significant advantages for the majority of patients. Premature induction of cytotoxic polychemotherapy may even cause disadvantages for subgroups of patients and should only be used as primary therapy in those situations, where urgent remission is mandatory. Only after all endocrine therapies have been tried and evaluated, one should turn to chemotherapy, whereby a trend towards "soft" chemotherapy, often as monotherapy, is favoured. The development of new substances, such as long acting LHRH analogues, "pure" antiestrogens with high receptor affinity, highly potent selective aromatase inhibitors and also the discovery of anti-progestins lead to further improvement of endocrine therapy in relation to efficacy as well as reduction of side effects. Adjuvant endocrine therapy with Tamoxifen correlates positively with the course of the disease and the survival rate in postmenopausal women. Unfortunately no effective adjuvant hormone therapy in premenopausal women exists to date.

Estrogenic Hormone Therapy in Advanced Breast Cancer.

Excerpt Physiologic doses of estrogenic hormone have been demonstrated to stimulate breast cancer in young women, thereby providing a rationale for castration as a therapy in premenopausal women wi...