Climacteric Patients Research Articles

A prospective study on women with a history of breast cancer and with or without estrogen replacement therapy

Objective: Because a categorical refusal of estrogen replacement therapy (ERT) from postmenopausal patients with a history of breast cancer is not based on any research evidence and may be more harmful than beneficial, we evaluated the safety and efficacy of ERT in these women. Methods: We recruited 131 patients who had been treated for breast cancer for a mean of 4.2 years (range 1 month to 20 years) before. Eighty-eight decided to use ERT, whereas 43 refused or had no need for ERT. At recruitment, the patients were carefully examined for breast and gynaecologic findings. Non-hysterectomized patients wishing to receive ERT ( n=54) then started using estradiol as oral tablets (2 mg/day) ( n=44) or as transdermal gel (1.5 mg/day) ( n=10) in combination with 10-day courses of oral medroxyprogesterone acetate at 4-week intervals, whereas hysterectomized patients ( n=34) used only estradiol, orally (2 mg/day) ( n=31) or transdermally (1.5 mg/day) ( n=3). The patients using ERT were carefully examined 6 and 12 months later, and then annually at a specific outpatient department, and the mean follow-up time is now 2.5 years (range from 1 month to 5.2 years, 216 woman-years). The 43 patients not wishing to receive ERT were followed annually at the oncologic department for a mean of 2.6 years (range from 1 month to 4.7 years), and served as a control group. Results: ERT significantly reduced climacteric symptoms, and the Kupperman score fell by 63%, from 26.9±8.6 to 9.9±6.7 (mean±SD). In non-hysterectomized women, medroxyprogesterone acetate triggered withdrawal bleeding in all except seven women. Seven patients (13%) experienced spotting during ERT. In 27 women, endometrial thickness exceeded 10 mm, and two of the total of 54 patients (3.7%) had simple hyperplasia. This vanished spontaneously in 3–6 months. Ten patients terminated the use of ERT within the first 12 to 39 months due to the lack of severe vasomotor symptoms ( n=4) or due to the recurrence of breast cancer or to cancer of the contralateral breast ( n=6). Eighty-one of the 88 patients (92%) using ERT showed no evidence of recurrence, whereas five patients (5.7%) had recurrence in 12–36 months and two patients (2.3%) developed a cancer of the contralateral breast in 14–24 months; another one of those wanted to continue with ERT. Thus the combined risk of recurrence or a new cancer of the contralateral breast in ERT users was 7/216 woman-years (3% per year). In the control group, 38 of 43 patients (88.4%) showed no evidence of recurrence or contralateral cancer, whereas four patients had recurrence and one developed a contralateral breast cancer (5/112 woman-years, 4% per year). Conclusions: Symptomatic climacteric patients with a history of breast cancer benefited from ERT without increasing their risk of recurrence, but the short follow-up and the small number of patients limit any definitive recommendations.

Fidedignidade do Teste-reteste na Aplicação do Índice Menopausal de Blatt e Kupperman

Purpose: based on the knowledge that the reliability of an instrument is essential for a correct interpretation of the results of research, the purpose of the present study is to evaluate the reliability of one of the menopausal indexes more often used in clinical practice and research, the Blatt and Kupperman Menopausal Index (BKMI). Methods: the population consisted of 60 climacteric patients attended at the Gynecology Outpatient Clinic of the Lauro Wanderley University Hospital of the Federal University of Paraiba in Joao Pessoa city. The reliability coefficient was analyzed by the test-retest method, whose application was done on two different occasions with an interval of four weeks, without administration of medicines. Results: the variation of the score observed with the application of BKMI at the first measurement was 2 to 41, with a median of 18 and mean of 18.8 (± 10.76), while at the second measurement, the menopausal index was 20.2 (± 10.51), median 19, and values ranging from 2 to 39. Despite these results, a Speaman (rs) coefficient of 0.68 (p = 0.001), which is a coefficient of only moderate intensity, was observed. Conclusions: the test-retest reliability in the application of the BKMI shows that, although this instrument presented a statistically moderate reliability, the intensity observed does not represent a reliable measurement. Considering that a correlational study is only a type of screening of the quality of a measurement method, we concluded that other studies must be performed with the purpose of evaluating the reliability and the validity of the BKMI. It is possible that the attribuition of different values to the items of BKMI and the inclusion of symptoms directly related to the estrogenic defficiency, like symptoms of vaginal atrophy, would make the instrument more reliable.

Medial frontal cortex hypoperfusion in climacteric patients

Medial frontal cortex hypoperfusion in climacteric patients

Benefit of a fixed drug combination containing St John's Wort and Black Cohosh for climacteric patients – results of a randomised clinical trial

Benefit of a fixed drug combination containing St John's Wort and Black Cohosh for climacteric patients – results of a randomised clinical trial

P069 Comparative assessment of endocrinologic stimulation tests (TRH; GH-RH) with patients at fertile age and climacteric patients

P069 Comparative assessment of endocrinologic stimulation tests (TRH; GH-RH) with patients at fertile age and climacteric patients

A Computerized Record for the Comprehensive Management of the Climacteric Patients

Pansini, F. M.D.; Bagni, B. M.D.†; Bentivoglio, R.*; Bonaccorsi, G. M.D.; Zanotti, L. M.D.; Albertazzi, P. M.D.; Mollica, G. M.D. Author Information

Endometrial and vaginal response to three different oestrogen preparations administered by the transdermal and oral routes

In a randomized, cross-over study endometrial and vaginal response to transdermal 17β-oestradiol (TTS-oestradiol 50 μg) and two forms of oral oestrogen replacement therapy (conjugated oestrogens 1.25 mg and oestradiol valerate 2 mg) were studied in 13 peri-menopausal and post-menopausal women. Five (5) of the women exhibited periodic ovarian function as evidenced by peripheral oestradiol and progesterone levels and were considered to be peri-menopausal. In the post-menopausal group of 8 women the bleeding pattern was more regular than among the peri-menopausal women. In the case of the post-menopausal group the number of days on which spotting and bleeding occurred was significantly lower during the administration of TTS-oestradiol than during treatment with conjugated oestrogens. This finding was paralleled by a significantly higher karyopyknotic index in the vaginal epithelium and significantly increased deoxyribonucleic acid (DNA) synthesis in the endometrial cells during treatment with equine oestrogens. No significant difference was seen in these indices when the effect of TTS-oestradiol was compared with that of oestradiol valerate. The study results in the post-menopausal group suggested a relationship between the intensity of the oestrogen treatment and not only the proliferation and maturation of the oestrogen target-organ cells but also the number of days on which bleedling occurred. It was concluded that a clear distinction needs to be made between peri-menopausal and post-menopausal women. In the present study the irregular ovarian activity among the peri-menopausal subjects precluded an unbiased assessment of the exogenous oestrogens. It is also likely that exogenous oestrogens exert a cumulative action with oestrogen secreted endogenously, interfere with the physiological events at the target organ level and induce uncontrollable endometrial bleeding. The complete cessation of ovarian activity may therefore have to be established before exogenous oestrogens are administered to climacteric patients.

Clinical profile of Org OD 14

The clinical profile of Org OD 14 ((7α,17α)-17-hydroxy-7-methyl-19-norpregn-5 (10)-en-20-yn-3-one) is remarkable in that the compound demonstrates simultaneous weak oestrogenic, androgenic and progestational activity after oral administration to animals. It was therefore studied to evaluate its efficacy in the treatment of the climacteric syndrome. Clinical data demonstrating these combined hormonal effects are reviewed in this paper: • - Administration of 2.5 mg/day Org OD 14 suppressed gonadotrophins in post-menopausal women and inhibited ovulation in fertile women. In post-menopausal women virtually no endometrial proliferation was induced, only occasional, very slight proliferation being seen. Even after 2 yr of therapy no endometrial hyperplasia was observed. A weak stimulatory effect on the vaginal mucosa was apparent. In addition, Org OD 14 prevented post-menopausal bone loss and alleviated vasomotor climacteric symptoms effectively. It also had a beneficial effect on mood and libido. • - Org OD 14 was well tolerated. The incidence of side effects (changes in body weight, vaginal bleeding) was low and similar to that with placebo treatment. Extensive safety studies of up to 5 yr duration, including liver function tests and metabolic studies, indicated no untoward effects. • - It was concluded that Org OD 14 is an effective and safe new preparation for the treatment of climacteric patients.

The Social and Psychological Origins of the Climacteric Syndrome.

The social and psychological origins of the climacteric syndrome. John G. Greene. Gower Publishing Company Ltd., Aldershot, U.K. and Brookfield, VT, 1984, 247 pp., $ 29.50. When I first became involved in research on the psychosocial aspects of the climacteric in 1969 I had only few studies to refer to. Only the study by Neugarten and coworkers (1963) and the study of Laszlo Jaszmann (1967) into the epidemiology of climacteric complaints, a study in which I had been indirectly involved, gave me some clues about the importance of social factors for symptom formation in the years around the menopause. Uninhibited therefore by too much knowledge, and largely ignorant about sociological techniques, I leapt into my first research project: a comparative study of attitudes towards the menopause in five European countries. When the results appeared I had progressed in my thinking, and guided by Jean Kellerhals, a sociologist who joined forces with me, we continued our expeditions into that unknown area: the climacteric as a psychosocial and cultural phenomenon. Now, fifteen years later, climacteric research has come of age. I am grateful to John Greene for having compiled this status quo report of work done in the past. The first chapters of this book, on terminology, on climacteric symptoms and oestrogen therapy are primarily intended, I think, to explain to the social scientist what the climacteric means in medical terms. Still, they are a useful introduction even for the medical researchers in this field. I was surprised to see how few good placebo-controlled, double-blind studies have been done into the effects of oestrogens on climacteric complaints. The author has reviewed these critically. With regard to effects of oestrogens on the psyche, the author concluded: “any psychotropic effect of oestrogen remains undemonstrated”. I tend to agree with that statement. Controlled studies have provided insufficient evidence for any such effect. Yet every clinician who has treated climacteric patients has been struck by the consistency in the effect of oestrogen therapy on psychic well-being of his patient. Obviously it is difficult to quantify such an effect, but I am sure that, in time, the evidence will be brought forward. Not only are well-controlled, double-blind clinical studies on the effect of therapy few in number, but also studies of the social, cultural and psychological factors influencing symptom formation at the climacteric are scarce. The advantage however, is that here the research done by different workers is often complementary, each study adding a piece or several pieces to the jigsaw puzzle. This book shows the jigsaw puzzle as it is today. The author has incorporated new ideas and findings concerning the effects of life events such as death in the natal family into the concept that has grown over the years. He comes to a synthesis and presents a model of vulnerability which is very attractive and allows us to identify which women are heading for a difficult climactaric and which are not. The

Effects of topical oestrogen therapy in post-menopausal climacteric patients : C.G. Netto, A.M. Fonseca, R. Hegg, N.R. Mello, J.R. Filassi, M.M. Okada, S.B. Zynnier and C.A. Salvatore - Sào Paulo, Brasil

Effects of topical oestrogen therapy in post-menopausal climacteric patients : C.G. Netto, A.M. Fonseca, R. Hegg, N.R. Mello, J.R. Filassi, M.M. Okada, S.B. Zynnier and C.A. Salvatore - Sào Paulo, Brasil

Vasoconstrictory thromboxane A 2 and vasodilatory prostacyclin in climacteric women: effect of oestrogen-progestogen therapy

The production of vasoconstrictory thromboxane A 2 (TxA 2) and vasodilatory prostacyclin (PG 2) was studied in women suffering from climacteric vascular instabilities before and during the oestrogen-progestogen therapy. The serum concentrations of TxB 2, a metabolite of TxA 2, in climacteric patients were similar (170.5 ± 25.5 ng/ml, mean ± SE, n = 14) to those in control subjects (196.0 ± 27.5 ng/ml n = 17) before the start of treatment, but rose to 209.3 ± 24.5 ng/ml after 3 wk of treatment ( P < 0.01 in comparison with the pre-treatment level), to 227.2 ± 44.1 ng/ml after 3 mth ( P < 0.05) and to 237.4 ± 30.3 ng/ml after 6 mth ( P < 0.05). The plasma concentrations of 6-keto-prostaglandin F 1a, a stable breakdown product of PG 2, were normal in climacteric patients (43.5 ± 7.3 pg/ml as against 46.1 ± 5.9 pg/ml) and did not change during replacement therapy. It was concluded, firstly, that climacteric symptoms are not accompanied by changes in TxA 2/PG 2 which can be detected in peripheral blood and, secondly, that the increase in the concentration of vasoconstrictory TxA 2 induced by oestrogen-progestogen therapy may contribute to the disappearance of climacteric vascular instabilities.

Ovarian failure and ageing

Summary It is difficult to separate the true symptoms of oestrogen deficiency from symptoms of ageing and the effects of social and domestic problems of the middle-aged woman, but a careful history eliciting vasomotor symptoms or atrophic vaginitis, or a recent onset of psychogenic symptoms, identifies the patient who might benefit from the only specific treatment of oestrogen deficiency — namely oestrogen. Response is usually dramatic and gratifying, and the good health regained rapidly becomes addictive, with patients unwilling to accept drenching night sweats, disturbed sleep and ensuing tiredness, lethargy, irritability, loss of concentration and depression, and relieved that they can once more function normally. The physician can also be reassured that there is no evidence in the medical literature that low-dose oestrogen therapy with additional cyclical progestogens, if the patient has a uterus, increased the incidence of endometrial cancer in climacteric patients; it may indeed reduce the incidence of cardiovascular problems, hypertension, osteoporosis and fractures. There remains a desperate need for well-controlled studies on the aged geriatric population to determine whether oestrogen therapy is of long-term benefit to the wellbeing of women, and to establish whether any protection from skeletal or cardiovascular pathology will reduce the duration of pitiful ‘pre-death dependency’ in this population.

CLONIDINE IN THE TREATMENT OF MENOPAUSAL SYMPTOMS

Twenty-five women suffering from climacteric complaints after surgical castration were treated with clonidine in a placebo controlled trial. Clonidine in the dose of 75 to 150 mug daily diminished the attack rates of flushing and sweating significantly. It can be recommended as a safe therapy for climacteric patients, at least those with contra-indications to oestrogen therapy.

A comparison of the influence of alpha-estradiol dipropionate and of estradiol cyclopentylpropionate on the vaginal mucosa of nonmenstruating and irregularly menstruating women

1.1. Twenty-seven women were treated with single injections of equivalent amounts of two estrogenic preparations to a total of 48 tests. In 32 tests changes occurred in the vaginal mucosa. No objective response followed 7 of the remaining 16 injections and 9 results had to be discarded.2.2. Alpha-estradiol dipropionate in sesame oil and estradiol cyclopentylpropionate in sesame oil were the estrogens employed in these tests. Each preparation was given in doses of 5 mg. by the intramuscular route.3.3. Daily vaginal smears were taken for a control period of one week or longer prior to therapy and were taken daily or every other day for an average period of not less than three weeks thereafter.4.4. The lag-time (days between the injection and the vaginal response) for each preparation ranged from one to seven days with an average of 3.7 days.5.5. The average duration in days of the vaginal response initiated by the injections of hormone was 17.8 days.6.6. The degree of follicular activity was greater following the administration of estradiol cyclopentylpropionate than after the use of alpha-estradiol dipropionate.7.7. The duration of the vaginal changes was correlated with the degree of lollicular stimulation observed rather than with the preparation employed.8.8. Climacteric patients reported symptomatic relief starting in from one to five days following the administration of cither estrogen and persisting for from one to eight weeks thereafter. Symptomatic relief lasted longer following the injection of the estradiol cyclopentylpropionate than it did after the administration of alpha-estradiol dipropionate.

Effects of Various Estrogenic Preparations: IV. Alpha-Estradiol Administered Intraorally in a Polyethylene Glycol Wax: Objective and Subjective Effects in Climacteric Women

Abstract 1.1. Forty-one women were treated with one or more injections of equivalent amounts of seven estrogenic preparations to a total of 57 tests. In thirty-nine tests, changes occurred in the vaginal mucosa; of these, however, seven were difficult to evaluate in relation to the administration of the estrogen. No objective response followed any of the remaining eighteen injections. 2.2. Free estrone, free estradiol, and the benzoic acid and dipropionic acid esters of the latter were the estrogens employed in these tests. Estrone was given in doses of 4 mg. and each estradiol preparation in amounts of 1 mg. per injection. Estrone was used as an equeous suspension only. Free estradiol was similarly employed, and also as a solution in propylene glycol and sesame oil, respectively. Estradiol dipropionate was prepared as a solution in sesame oil only; the benzoate was administered in menstrua of peanut oil and propylene glycol, respectively. 3.3. Daily vaginal smears were taken for a control period of approximately one week prior to therapy and for an average period of ten days thereafter. Approximately 900 smears were studied. 4.4. The average lag-time (hours between injection and vaginal response) for each preparation was as follows: estradiol dipropionate in sesame oil, 88; estradiol benzoate in peanut oil, 90; estradiol in aqueous suspension, 90; estrone in aqueous suspension, 100; estradiol in sesame oil, 108; estradiol in propylene glycol, 114; and estradiol benzoate in propylene glycol (one case), 120. 5.5. The average duration in hours of the vaginal response initiated by estradiol dipropionate in sesame oil was 100; by estradiol benzoate in peanut oil, 82; by estradiol in sesame oil, 36; by estradiol in propylene glycol, 120; by estradiol in aqueous suspension, 109; and by estrone in aqueous suspension, 110. 6.6. The degree of follicular activity varied widely with the preparation used and from subject to subject, but in any given instance, was directly proportional to the duration of the vaginal changes. 7.7. Climacteric patients reported symptomatic relief starting one to three days following injection and persisting for from three to ten days thereafter.

The effects of various estrogenic preparations: III. The influence of equivalent amounts of several estrogens on the vaginal mucosa of nonmenstruating women

1.1. Forty-one women were treated with one or more injections of equivalent amounts of seven estrogenic preparations to a total of 57 tests. In thirty-nine tests, changes occurred in the vaginal mucosa; of these, however, seven were difficult to evaluate in relation to the administration of the estrogen. No objective response followed any of the remaining eighteen injections.2.2. Free estrone, free estradiol, and the benzoic acid and dipropionic acid esters of the latter were the estrogens employed in these tests. Estrone was given in doses of 4 mg. and each estradiol preparation in amounts of 1 mg. per injection. Estrone was used as an equeous suspension only. Free estradiol was similarly employed, and also as a solution in propylene glycol and sesame oil, respectively. Estradiol dipropionate was prepared as a solution in sesame oil only; the benzoate was administered in menstrua of peanut oil and propylene glycol, respectively.3.3. Daily vaginal smears were taken for a control period of approximately one week prior to therapy and for an average period of ten days thereafter. Approximately 900 smears were studied.4.4. The average lag-time (hours between injection and vaginal response) for each preparation was as follows: estradiol dipropionate in sesame oil, 88; estradiol benzoate in peanut oil, 90; estradiol in aqueous suspension, 90; estrone in aqueous suspension, 100; estradiol in sesame oil, 108; estradiol in propylene glycol, 114; and estradiol benzoate in propylene glycol (one case), 120.5.5. The average duration in hours of the vaginal response initiated by estradiol dipropionate in sesame oil was 100; by estradiol benzoate in peanut oil, 82; by estradiol in sesame oil, 36; by estradiol in propylene glycol, 120; by estradiol in aqueous suspension, 109; and by estrone in aqueous suspension, 110.6.6. The degree of follicular activity varied widely with the preparation used and from subject to subject, but in any given instance, was directly proportional to the duration of the vaginal changes.7.7. Climacteric patients reported symptomatic relief starting one to three days following injection and persisting for from three to ten days thereafter.

ORAL THERAPY WITH ETHINYL ESTRADIOL IN THE MENOPAUSE

T HE value of estrogenic preparations in the treatment of the menopausal syndrome is firmly established. Ever since chemically pure estrogens became available, the medical profession has sought earnestly for compounds which, when given orally, have the distinction of high potency, good tolerability, and economy. In 1938, Inhoffen and Hohlweg3 prepared a derivative of estradiol by replacing the hydrogen atom at carbon atom 17 with an ethinyl group. It is claimed that the new compound fulfills the requirements of great effectiveness when administered by mouth, of comparative absence of unpleasant “side reactions, and of inexpensiveness. Clinical results with ethinyl estradiol in climacteric patients have been described only by a limited number of investigators ; hence a report of further experiences along these lines seems warranted.

Oral therapy with ethinyl estradiol in the menopause

T HE value of estrogenic preparations in the treatment of the menopausal syndrome is firmly established. Ever since chemically pure estrogens became available, the medical profession has sought earnestly for compounds which, when given orally, have the distinction of high potency, good tolerability, and economy. In 1938, Inhoffen and Hohlweg3 prepared a derivative of estradiol by replacing the hydrogen atom at carbon atom 17 with an ethinyl group. It is claimed that the new compound fulfills the requirements of great effectiveness when administered by mouth, of comparative absence of unpleasant “side reactions, and of inexpensiveness. Clinical results with ethinyl estradiol in climacteric patients have been described only by a limited number of investigators ; hence a report of further experiences along these lines seems warranted.

Effect of Estradiol and Diethylstilbestrol upon the Atrophic Human Buccal Mucosa with a Preliminary Report on the Use of Estrogens in the Management of Senile Gingivitis

IT HAD BEEN noted by one of us (A. R. A) that many climacteric patients complain of a dryness or burning sensation in the mouth. Following therapy with estradiol or diethylstilbestrol, these symptoms would disappear. An investigation of the literature disclosed that the reports on this subject were few. Nathanson and Weisberger (1) clearly described the associated gross lesions before and after treatment with estradiol, but they made no report of a microscopic study. In the castrated female monkey, Ziskin described stimulation and growth of the gingival mucosa following treatment with estrone and estradiol (2). In the human female, on the basis of a single biopsy specimen from each of 3 patients receiving estradiol, Ziskin concluded that estrogen stimulates growth and keratinization of the gingival mucosa (3). These studies were made in view of the incomplete reports on mucosal response to estrogens in human beings. Estradiol and diethylstilbestrol were used in order to determine if there was any differen...

Therapy of the Menopause

SINCE the universal appreciation of the value of estrogens in the endocrine management of the menopause, many commendable efforts have been made to simplify this organotherapy. The search for the most effective estrogens has yielded a number of useful natural and synthetic compounds. The objective sought is one producing maximum symptomatic relief with a minimum of hazard and inconvenience to the patient. These prerequisites are highly desirable because of the chronicity of the menopausal syndrome. To simplify the therapy of the large numberof climacteric patients in this clinic, we have attempted in the past 10 years to limit the estrogens used to the orally effective, naturally occurring compounds, assuming that these are more physiologic for the treatment of the varied menopausal disturbances. We have not tested the newer synthetic steroid hormones nor have we used estrone pellets subcutaneously. Of the various natural estrogenic compounds previously used, the most satisfactory proved to be a product c...