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Query: UMLS:C0006826 (cancer)
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The menopause is centered on the ovary and its in-built obsolescence. The events of the menopause start when the active ovary begins to fail and end when the ovary lapses into inactivity. The duration of these events is variable. Stimulated by the pituitary, 1 follicle develops each month as a hormone-producing organ. The life span of the follicle is then 28 days. Follicles continue to develop unt il none respond to the stimulus of the pituitary. The 32-week fetus has about 7 million primordial follicles. At birth, the number has dropped to 2 million. By puberty only 300,000 3008000 remain. During adult life about 400 follicles will have provided the ova and the hormones. The last few capable of funtion may have poor endocrine function. Ovarian activity is controlled by a "biological clock" in the hypothalamus. This controls the pituitary by a gonadotropin-releasing h ormone. In response the pituitary secretes follicle stimulating hormone (FSH) and luteinizing hormone (LH). The creation of the corpus luteum follows in the ovary and secretes progesterone while estrogen secretion continues. A cyclic drop in pituitary gonadotropin secretions causes the corpus luteum to degenerate. The ovary makes estrogen from cholesterol, converting it to pregnenolone, then to progesterone which is androstenedione to andnostenedione and on to estradiol. Estradiol is the estrogen secreted by the ovary, but it can be changed in the liver t o estrone and estriol. The pathways of the steroid hormone synthesis are the same in the adrenal cortex. When estrogen deficiency occurs in the menopause LH levels increase. Later the FSH is raised and remains high for the rest of life. This raised FSH and low estrogen levels appear to cause the characteristic hot flashes. Abrupt deprivation of estrogen causes more symptoms than a slow decline of function. Estrogen therapy may relieve these symptoms. Prevalence of coronary thrombosis rises sharply in the postmenopausal years. Estrogen-containing pills increase the incidence of venous thrombosis. Estrogen therapy reverses the atrophy of the genital tract. Cycles of treatment imitate the normal action of the functioning ovary but usually are not large enough to promote menstruation. Endometrial cancer appears to be increased by estrogen therapy. It may be that the addition of progesterone would protect against this from of cancer. The adjustment of tissues to an altered hormonal environment and the unrelated changes of aging make complicated problem.
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PMID:The menopause: the events of the menopause. 95 89

Twenty-five evaluable patients with advanced or recurrent epithelial ovarian carcinoma that was no longer controllable with surgery, radiation therapy, and/or chemotherapy were treated with leuprolide acetate, a gonadotropin-releasing hormone agonist, 1 mg subcutaneously daily. One partial response (4%) was observed among the 25 patients. The upper 95% confidence bound of the response rate is 17.6%. Fifteen patients (60%) exhibited stable disease for at least 8 weeks, and 9 patients (36%) developed progressive cancer while receiving treatment. The regimen was well tolerated with no patient experiencing life-threatening toxicity. Mild toxicities included leukopenia in 2 patients (8%), thrombocytopenia in 2 patients (8%), gastrointestinal toxicity in 5 patients (20%), anemia in 4 patients (16%), hot flashes in 1 patient (4%), and facial swelling in 1 patient (4%). Thus, leuprolide acetate was well tolerated but has insignificant activity in treating patients with chemotherapy-refractory ovarian adenocarcinoma.
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PMID:A phase II trial of leuprolide acetate in patients with advanced epithelial ovarian carcinoma. A Gynecologic Oncology Group study. 155 99

We report preliminary results for the first 164 patients enrolled in a multicenter study comparing the endocrine effects, efficacy, and safety of 3.6 mg of goserelin acetate (Zoladex) and orchiectomy in patients with Stage D2 prostate cancer. Eighty-one patients were randomly allocated to receive Zoladex and 83 to orchiectomy. The median follow-up time for all patients was two hundred ten days. Median serum levels of testosterone were reduced to castrate levels (less than 50 ng/dL) within four weeks in both groups and remained suppressed for up to sixty weeks. An objective response according to modified criteria of the National Prostatic Cancer Project was observed in 81 percent and 78 percent of patients in the Zoladex and orchiectomy groups, respectively. There were no statistically significant differences between treatment groups in the distributions of time to treatment failure or time to disease progression. The most commonly reported adverse events in both treatment groups were hot flashes, cancer-related pain, unspecified pain, and urinary symptoms. These results suggest that Zoladex may offer an alternative to orchiectomy in the treatment of advanced prostate cancer.
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PMID:Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Zoladex Prostate Study Group. 182 32

A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted. The most common side effects were nausea (31%), vomiting (12%), and hot flashes (29%). Five patients were removed from the study for possible adverse reactions: three patients experienced hypercalcemia; one experienced tremulousness, fatigue, and inability to think clearly; and one had vaginal bleeding. Twelve patients died while on study, 11 with disease progression and one with a pulmonary embolus. Sex hormone-binding globulin (SHBG) levels increased and there was a modest decline in serum antithrombin III levels. Four of 48 assessable patients had partial responses: three with breast cancer and one with endometrial cancer. Toremifene was generally well tolerated at the doses tested.
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PMID:Phase I study of toremifene in patients with advanced cancer. 183 8

Two hundred sixty-five women estimated the likelihood that they would take estrogen plus progestin to alleviate menopausal symptoms when faced with hypothetical cases varying in degree of hot flashes and risk of osteoporosis and cancer. Clustering of their judgment policies revealed four groups of women with respect to their approach to this decision. These groups of women were significantly different from each other on educational level, perceived experience of stress, and attitudes toward menopause and use of medications. Willingness to take hormonal therapy across all cases was related to attitudes about, and knowledge of, menstruation, perceived stress, mother's experience with menstrual problems, severity of symptoms, and use of vitamins. While there have been previous attempts to cluster rater policies, the current study represents a novel attempt to understand the differences between people who appear to have different policies about a decision problem, in this case, whether or not to take hormone therapy to counter menopausal symptoms.
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PMID:Capturing and clustering women's judgment policies: the case of hormonal therapy for menopause. 203 Feb 80

The efficacy and side-effects of megestrol acetate and medroxyprogesterone acetate in postmenopausal patients with advanced breast cancer were compared in a prospectively randomized study. The dosage of MA was 2 X 80 mg p.o. or MPA 2 X 500 mg p.o. daily, given as a secondary hormonal treatment, mostly after previous treatment with tamoxifen. Ninety-eight patients entered the study and 92 were evaluable for effect, 48 patients on MA and 44 on MPA. Age, main tumor site and prior treatment were not different, but there was a preponderance of ER-negative tumors in the MA group. Responses appeared to be more frequent in the MPA-treated group (25% vs. 43%), predominantly in bone lesions, 12% for MA and 45% for MPA. Median progression-free survival was comparable, 15 vs. 10 months, and overall survival was not different (20 vs. 16 months). Toxicity was frequent, occurring in 83% vs. 74% of patients: increased appetite, nausea and dizziness in more than 20%, and a preponderance of pyrosis and breathlessness on MA and hot flashes, sweating and tremors on MPA. Cushingoid symptoms were present in about a quarter of the patients treated for more than 3 months. The occurrence of thrombo-embolic episodes and cardiovascular events was evenly distributed. Patients on MPA had more often increase in body weight, systolic blood pressure and serum creatinine than those treated with MA. It is concluded that MPA may be more effective for treatment of bone metastases, at the expense of more progestational side-effects. The occurrence of Cushingoid effects is frequent but similar in both arms, while the incidence of cardiovascular or thrombo-embolic events cannot be related to the use of either compound.
Eur J Cancer 1990 Mar
PMID:A randomized comparison of megestrol acetate (MA) and medroxyprogesterone acetate (MPA) in patients with advanced breast cancer. 214 91

For perimenopausal women, an important decision is whether or not to use hormone replacement therapy (HRT). The decision is complex because HRT involves judgment in weighing gains and losses related to physiological risk. Gains involve relief of hot flashes and prevention of osteoporosis; losses include cancer mortality and side effects of medication. A policy-capturing study of 283 perimenopausal women showed that the factor of most frequent concern was relief of hot flashes. Cluster analyses identified four major groups. Group 4 had an n of 9 and the lowest R2, making interpretation of data questionable. The largest group responded to hot flashes alone; the second to hot flashes and osteoporosis; and the third to hot flashes, somewhat to osteoporosis, but also to side effects of estrogen/progestin therapy. Results indicate nursing interventions should anticipate differences in women's concerns and tailor counseling appropriately.
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PMID:Women's use of information regarding hormone replacement therapy. 227 Mar

Thirty postmenopausal patients who had evaluable estrogen receptor-positive or unknown metastatic breast cancer were treated with cyclic sequential combined hormonal therapy consisting of 50 micrograms of ethinylestradiol orally daily for 7 days followed by 400 mg of medroxyprogesterone acetate orally daily for 21 days, followed in turn by 7 days of rest. Cyclic administration was continued until progressive disease was detected. Patients who had had one previous chemotherapy regimen were included, but 63% of patients were previously untreated. Six patients achieved complete remission and 11, a partial remission, for an overall response rate of 57%. Median remission duration was 22 months; median time to disease progression for all 30 patients was 8 months. Toxicity consisted of cyclic vaginal bleeding, hot flashes, weight gain, irritability, and fluid retention. This cyclic, sequential hormonal regimen was effective and well tolerated.
Cancer 1989 Sep 01
PMID:Sequential cyclic combined hormonal therapy for metastatic breast cancer. 252 85

Ovarian failure may be a long-term consequence of cancer treatment for premenopausal women. Caused by several treatments, including radiation therapy and the alkylating agents, it produces signs and symptoms associated with menopause: hot flashes, amenorrhea, dyspareunia, loss of libido, and irritability. Critical factors that determine ovarian functioning after treatment for cancer are the patient's age at the time of therapy, the amount of radiation that the ovaries received, and the dose of the antineoplastic agent(s). Medical interventions, such as hormonal therapy and surgical repositioning of the ovaries, may maintain ovarian function for some women. Nursing intervention includes assessment, education, and counseling. Counseling focuses on how the prematurely menopausal patient feels about herself as indicated by self-esteem, body image, and sexuality.
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PMID:Ovarian failure and cancer treatment: incidence and interventions for premenopausal women. 278 Apr 1

A patient with adenoid cystic carcinoma was treated with mitoxantrone at a dose of 12 mg/m2 every 3 weeks. After the fifth dose, she developed amenorrhea accompanied by vasomotor instability (hot flashes). Subsequent serum gonadotropin and estradiol levels confirmed the postmenopausal state. The mechanism of mitoxantrone-associated amenorrhea is most likely due to direct toxic effects on the ovary, as is seen with other forms of chemotherapy. Ovarian dysfunction with mitoxantrone has not been previously reported. The important consequences of chemotherapy-induced ovarian failure are described. This toxic effect may be more frequently described as the drug becomes more widely available.
Cancer Treat Rep 1986 May
PMID:Possible mitoxantrone-induced amenorrhea. 301 Dec 60


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