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Biomedical subjects

A A Haspels

Publications and source records attributed to A A Haspels.

At least 19 recordsLinked to original sources

Biochemical and histological effects of vaginal estriol and estradiol applications on the endometrium, myometrium and vagina of postmenopausal women.

Estrogen and progesterone receptors in the cytosol (ERc, PRc) and estrogen receptors in the nuclear compartment (ERn) were measured in the endometrium, myometrium and vagina of 29 postmenopausal women who underwent hysterectomy. The effects of vaginal estriol (0.5 mg daily) compared to 17 beta-estradiol (0.05 mg daily) therapy on these receptor levels were studied. In addition, the endometrium was examined by light microscopy for estrogenic stimulation. We found biochemical and histological signs of estrogenic stimulation in all three tissues after estradiol as well as estriol therapy. In the vagina the effect of both estrogens on the ERc concentration was different from that in the endometrium and myometrium. The effects of estradiol and estriol on the ERn were comparable in all three tissues. The PRc levels increased significantly in all tissues after estrogen therapy; in the myometrium it was significantly higher after estriol than after estradiol applications. In conclusion, there were no clear differences between vaginal estradiol and estriol medication with regard to the effects on receptor levels in vaginal and uterine tissues. In the histological studies at the light microscopy level similar signs of estrogen stimulation of the endometrium were found following estradiol and estriol medication.

Administration, Intravaginal↗

Endometrial response in estrogen replacement therapy quarterly combined with a progestogen.

OBJECTIVE: The aim of the study was to investigate the endometrial histology and the bleeding pattern under a hormone replacement therapy regimen with continuous estrogen quarterly (3-monthly) combined with a progestogen. METHODS: In a prospective, double-blind, randomised clinical trial, 30 healthy, postmenopausal women were allocated to one of the three trial preparations. Group I was treated with 1 mg micronized 17 beta-estradiol continuously, group II took 2 mg micronized 17 beta-estradiol continuously and group III took 1 mg and 2 mg 17 beta-estradiol alternating every 42 days (step-up regimen). One treatment cycle was 84 days, during the last 12 days estradiol was combined with 50 micrograms gestodene. The total treatment period comprised two cycles of 12 weeks each. With regard to endometrial histology, the second cycle was the actual study cycle. In each patient endometrial samples were obtained at the following time points: after the withdrawal bleeding in the beginning (day 8-11) of cycle II (Vabra-method), at the end of the estrogen mono-phase (day 70-72) of cycle II(Pipelle-method), and 8-11 days after cessation of all medication (Vabra-method). Histopathological classification was done by two experienced gynaecological pathologists. All patients kept record of their bleeding events in a diary. Analysis of variance and Kruskal-Wallis test were used for statistical analysis of the data. RESULTS: 29 patients were evaluable for the assessment of endometrial histology. Only one sampling procedure (1.2%) yielded an insufficient amount of tissue. In each treatment group, simple (cystic) hyperplasia was observed exclusively at the end of the estrogen mono-phase (in total 4/29 patients, 14.8%). Hyperplasia disappeared in all cases after the combined estrogen-progestogen phase. No cytological atypia was seen. Fifty-five cycles were evaluable for the bleeding pattern. The onset of the scheduled bleeding (withdrawal bleeding) was in all cycles on day 11 of the combined phase or beyond. Unlike the duration, the severity of the scheduled bleeding episodes was estrogen-dose dependent. In the entire treatment period of 2 x 84 days, breakthrough bleeding occurred in 3 women, totalling 9 days. Spotting occurred rarely and was equally divided among the treatment groups. CONCLUSIONS: A quarterly sequential hormone replacement therapy regimen for women with anintact uterus gives rise to the development of simple hyperplasia without cytological atypia at the end of the unopposed estrogen phase. This occurs independent of the estrogen dose and can be reverted to inactive or atrophic endometrium by the addition of gestodene during 12 days. The combination offers good cycle control. The safety aspects should be investigated further in long-term studies before this regimen can be advocated for routine use.

Analysis of Variance↗

Emergency contraception: a review.

In the Netherlands, many women use a postcoital method of contraception in "emergency" situations. Postcoital contraception started in the 1960's with the administration of large doses of estrogens: 50 mg diethylstilbestrol for 5 days or 5 mg ethinylestradiol for 5 days. In the eighties, a double-blind study compared the original hormonal therapy of 5 mg ethinylestradiol for 5 days with a combination pill containing just 0.1 mg in combination with 1 mg d1-norgestrel, of which two doses are give, the second 12 hours after the first. This method was as effective in preventing pregnancy as the original treatment with high estrogen dosage. Moreover, it resulted in women suffering less nausea and vomiting. One study from Hong Kong indicated that levonorgestrel without ethinylestradiol was as effective as the combination. Postcoital use of an intrauterine device to prevent pregnancy can be used as an alternative to the hormonal method. A recent development is the use of an antiprogestagen pill: 600 mg Mifepristone on day 27 of the cycle; side effects are minimal and the success rate is high. Mifepristone should be registered and made available in all countries for this indication.

Contraceptives, Oral, Combined↗

Hysterectomized women with ovarian conservation report more severe climacteric complaints than do normal climacteric women of similar age.

OBJECTIVE: Our purpose was to compare the severity of typical climacteric complaints (vasomotor complaints and vaginal dryness) and 21 other complaints, considered atypical for the climacteric, in women with and without a uterus. STUDY DESIGN: A cross-sectional population questionnaire survey was sent to all women aged 39 through 60 years in Ede, the Netherlands. Subjects were 986 hysterectomized women (one or both ovaries present) and 5636 normal women (uterus and both ovaries present). Statistical analysis was performed by cross tabulations, chi 2 analysis, analysis of variance, meta-analysis of variance, and ratios. RESULTS: Hysterectomized women, especially those aged 39 to 41 years, report significantly more vasomotor complaints, vaginal dryness, and atypical complaints than do normal climacteric women of the same age. The higher prevalence of typical climacteric complaints in hysterectomized women largely explains their higher level of atypical complaints. CONCLUSION: Physicians should be alert to typical climacteric complaints after hysterectomy with ovarian conservation, especially in young women, because the literature indicates that hysterectomized women with ovarian conservation are overrepresented with regard to osteoporosis, cardiovascular disease, osteoarthritis, depression, and sexual problems.

Adult↗

Impact of climacteric on well-being. A survey based on 5213 women 39 to 60 years old.

OBJECTIVE: Our aim was to assess the influence of the severity of vasomotor complaints, menopausal status, and age on the severity of 21 general complaints considered atypical for the climacteric. STUDY DESIGN: A cross-sectional general population survey was conducted through questionnaires of 5213 women aged 39 to 60 years. Statistical analysis was performed by cross tabulation, analysis of variance, and multiple regression analysis. RESULTS: Severity of vasomotor complaints is related to the severity of all 21 general complaints, most pronounced for tenseness and tiredness. Because menstruating women report more severe atypical complaints than nonmenstruating women with similarly severe vasomotor complaints, the change in prevalence of atypical complaints according to menopausal status is rather small. Adjusted for vasomotor complaints, there is virtually no independent effect of age on atypical complaints. CONCLUSIONS: Severity of vasomotor complaints is related to an overall reduced well-being. When climacteric women are seen for atypical complaints it is vital to assess the severity of vasomotor complaints also because others have shown that the severity of vasomotor complaints is indicative of the rate of climacteric bone loss.

Adult↗

Is premenstrual syndrome an endocrine disorder?

To both patients and physicians it seems natural to attribute adverse premenstrual phenomena to cyclic fluctuations of hormones produced by the ovary. This seems so plausible that, although the endocrine mechanism that causes premenstrual syndrome remains unknown, the condition itself is often treated with hormonal substances. Psychosocial factors are thus considered to be of only secondary importance. They may play a role as a contributing factor, to the 'real' cause of premenstrual syndrome they are not an essential ingredient. The aim of this review article is to examine how strong the evidence is for the possible existence of an endocrine factor as the causative agent in premenstrual syndrome. Using an epidemiological approach we conclude that the continuing search for the responsible mechanism that causes premenstrual syndrome may very well be an endocrine 'Holy Grail'. Human behavior cannot be understood within a single (hormonal) frame of reference. Cyclical ovarian activity is only one of the etiological factors in premenstrual syndrome. Unravelling the pathogenesis of premenstrual syndrome requires a multidisciplinary approach.

Causality↗

A simple strategy to detect significant premenstrual changes.

The prevalence of the ten most prominent premenstrual symptoms (top-ten) was calculated in Dutch women (n = 202), who considered themselves to suffer from complaints related to menstruation. Premenstrual syndrome was diagnosed where the scores of 5 or more of the top-ten symptoms showed an increase of at least 2 points (on a visual analog scale rated from 1 to 10) from day 12 to day 26 during two consecutive cycles. This diagnosis was confirmed in almost all subjects using a 'gold standard' criterion of an increase of at least 30% in complaints from the follicular phase to the luteal phase. In contrast to the latter strategy the 'top-ten' method successfully excluded women who felt free from premenstrual complaints. It is concluded that the 'top-ten' method is a simple and valid strategy to detect significant premenstrual changes.

Analysis of Variance↗

Effects of mefenamic acid on menstrual hemostasis in essential menorrhagia.

Prostaglandin synthesis inhibitors decrease menstrual blood loss by 30% to 50% in patients with essential menorrhagia. To obtain insight into their mechanism of action, we measured menstrual blood loss in menorrhagic women, who were receiving mefenamic acid (500 mg, three times daily) (n = 6) or placebo (n = 5) in a double-blind way. In addition we studied the morphology of early menstrual hemostasis. The subjects' uteri were extirpated in the first 24 hours of menstruation, and light and electron microscopy were used to perform morphologic and morphometric studies. In the group treated with mefenamic acid mean menstrual blood loss was decreased by 40%. In uteri of the women treated with mefenamic acid hemostatic plugs were further transformed, and fewer vessels without a plug were observed than in uteri of the group receiving placebo. These data suggest that mefenamic acid may act through an improvement of platelet aggregation and degranulation and through increased vasoconstriction.

Adult↗

Calcitonin gene-related peptide, the menstrual cycle and premenstrual syndrome.

Calcitonin gene-related peptide plasma levels were measured during four different phases of ovulatory menstrual cycles, in eight women suffering from the premenstrual syndrome and in eight controls. No significant fluctuations in calcitonin gene-related peptide levels occurred during the menstrual cycle. Neither were there significant differences in calcitonin gene-related peptide levels between the premenstrual syndrome and control groups.

Adult↗

Is 1 mg of estradiol valerate or 0.625 mg of conjugated estrogens sufficient for all women to prevent menopausal bone loss?

Bone mineral content was measured by dual photon absorptiometry in 35 women who needed estrogen replacement therapy but did not want the addition of progestogens because they did not want regular bleeding. A total of 23 women were treated with estradiol valerate 1 mg per day over a mean period of 3.7 years; 12 women received conjugated estrogens 0.625 mg per day over a mean period of 5.3 years. The mean values of bone mineral content in both groups did not change. In the women on estradiol valerate, 61% had a decrease, and in those on conjugated estrogens, 67% had a decrease in bone mineral content. However, the calculated decrease per year was within the limits of the intraindividual reproducibility of the measurements. A difference between two measurements with a decrease of > 1.0 g hydroxyapatite/year over a period of > 3 years is larger than the limits of the intraindividual reproducibility. A decrease in bone mineral content > 1.0 g hydroxyapatite/year over a mean period of 3.98 years, SD 0.35, was observed in six of 23 (26%) of the women on estradiol valerate with a mean decrease of 5.28 g hydroxyapatite, SD 0.97. Only one of 12 (8%) of the women on conjugated estrogens had a decrease of 6.1 g hydroxyapatite over a period of 5.2 years. Periodic measurement of bone mineral is recommended in women on estrogen replacement therapy with estradiol valerate 1 mg per day or conjugated estrogens 0.625 mg per day for prevention of postmenopausal bone loss.

Adult↗

Postcoital contraception.

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Antineoplastic Combined Chemotherapy Protocols↗

Morphology of menstrual hemostasis in essential menorrhagia.

We performed a morphologic and morphometric study with light and electron microscopy on early menstrual hemostasis in five menorrhagic uteri and one control uterus, related the data to measured menstrual blood loss and compared the data with our previous study on normal menstruation. Menstrual blood loss ranged from 39 to 234 ml. Menorrhagic uteri contained large hemostatic plugs, protruding with a large part into the extravascular space. These plugs often consisted of loosely packed, poorly degranulated platelets with few fibrin fibers. Recanalized plugs, consisting of fibrin fibers and platelet remnants at the periphery of the vessel, were also observed in menorrhagic uteri. Using morphometry, we demonstrated a positive correlation between menstrual blood loss and the number of occlusive and nonocclusive hemostatic plugs, but not with other aspects of hemostatic plug formation such as the vessel area occluded by the plug, plug transformation, or intra- or extravascular localization of the plug. Vasodilation or endometrial height were not correlated with the amount of menstrual blood loss. These data suggest that essential menorrhagia is associated with fragile hemostatic plugs or with more extensive vessel damage.

Adult↗

Measured menstrual blood loss in women with a bleeding disorder or using oral anticoagulant therapy.

Bleeding disorders in women are associated with a high incidence of menorrhagia, but few objective data exist. Whether oral anticoagulant therapy in women is also associated with a higher incidence of menorrhagia is unknown. We measured menstrual blood loss in six women with various congenital or acquired bleeding disorders and in 11 women treated with oral anticoagulant therapy. Mean menstrual blood loss in women with a bleeding disorder was 219 ml (range, 60 to 568 ml); five women had menorrhagia. In women treated with oral anticoagulant therapy, mean menstrual blood loss was 98 ml (range, 9 to 239 ml), and five women had menorrhagia. Of the six women with normal menstrual blood losses, two had losses in the high normal range (60 to 80 ml). No correlation existed between anticoagulant state and menstrual blood loss. The data support the close association between bleeding disorders and menorrhagia and suggest that oral anticoagulants increase menstrual blood loss.

Administration, Oral↗

Effects of seven low-dose combined oral contraceptives on sex hormone binding globulin, corticosteroid binding globulin, total and free testosterone.

The effect of seven low-dose oral contraceptive preparations on sex hormone binding globulin (SHBG), cortisol binding globulin (CBG), total and absolute free testosterone were investigated in groups of 10 healthy volunteers. All preparations contained about the same amount of ethinylestradiol but they differed in type and/or dose of progestagen. The progestagens studied were: levonorgestrel (LNG; in mono- and triphasic preparations), norethisterone (NET; in monophasic preparation), desogestrel (DSG; in mono- and biphasic preparations) and gestodene (GSD; in triphasic preparation), all 19-nortestosterone derivatives, and the anti-androgen cyproterone acetate (CPA) in a monophasic preparation. Differences observed in SHBG level, which reflect the estrogen-androgen balance, can be attributed to the intrinsic androgenic (or anti-androgenic) properties of the progestagens, and were in agreement with the results of published receptor binding studies, performed in vitro. Based on our results the following ranking (high to low) can be made with respect to the androgenicity of the preparations: monophasic LNG greater than or equal to monophasic NET = triphasic LNG greater than or equal to triphasic GSD = biphasic DSG = monophasic DSG greater than monophasic CPA. An anti-estrogenic effect of the 19-nortestosterone derived progestagens can be excluded by the effect on CBG, a marker for estrogenic activity. All preparations containing a 19-nortestosterone derived progestagen, independent of their type and dose, induce a similar rise in CBG, whereas the preparation with cyproterone acetate induced an even higher CBG level. Irrespective of the effect on total testosterone, which varies between the preparations, the absolute free testosterone level decreased to a comparable degree for all preparations.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Late second trimester abortion with 16,16-dimethyl-trans-delta 2-PGE1 methyl ester (gemeprost).

The use of gemeprost (16,16-dimethyl-trans-delta 2-PGE1 methyl ester) vaginal pessaries for the termination of pregnancy in the late second trimester has been investigated in an open single-center study. Of 56 nulliparous women between 18 and 22 weeks amenorrhoea, 33 (58.9%) aborted after the administration of 1 mg gemeprost pessaries; 5 women did abort after 3 doses, 10 after 4 doses and 18 after 5 doses. There was no statistical correlation between gestational age and abortion. The mean induction-abortion interval was 15.2 hrs (range 8.5-20.3 hrs). There were no serious complications. The safe induction of therapeutic abortion in 58.9% of women using vaginal gemeprost pessaries alone offers an acceptable alternative to surgical evacuation in the late second trimester but should not be started without the possibility to terminate the procedure by dilatation and evacuation (D + E).

Abortifacient Agents↗