Reversal by medical treatment of endometrial hyperplasia caused by estrogen replacement therapy.

OBJECTIVE: Endometrial hyperplasia, an entity considered a precursor to endometrial carcinoma, frequently develops in women receiving unopposed estrogens. Progestins used concomitantly with estrogens can largely prevent endometrial hyperplasia and carcinoma. However, the ability of progestins to reverse endometrial hyperplasia induced by estrogens is less well recognized. The purpose of this study was to assess the medical reversal rate of endometrial hyperplasia that develops in women receiving unopposed estrogen replacement therapy (ERT). DESIGN: Review of recent literature (1990-2000). RESULTS: Based on four large series, more than 90% of endometrial hyperplasia caused by ERT can be reversed by medical treatment. Discontinuation of estrogen and oral administration of 10 mg/day of medroxyprogesterone acetate continuously for 6 weeks or cyclically for 3 months (2 weeks of each month) are the two regimens most widely used. Other progestins also have been shown to be effective. CONCLUSIONS: Progestins are highly successful in reversing endometrial hyperplasia caused by ERT.

Use of a new transdermal delivery system for estrogen replacement therapy in postmenopausal women.

This study reports on the use of a new transdermal delivery system for estrogen replacement therapy. This was a 12 week open multicenter trial using patches that delivered 0.05 mg/24 hour of 17 beta-estradiol applied twice weekly, every 72 hours, with one week interval after each 3 weeks. Results indicate an overall significant improvement on climacteric complaints with a highly significant and time-related reduction in the two most frequent symptoms: hot flushes and night sweating. Neither local nor systemic side effects were prevalent. By the end of treatment mean plasma levels of estradiol and FSH were 50.6 pg/ml and 46.8 mIU/ml, respectively. It is concluded that this new system of transdermal estrogen replacement therapy significantly reduces the main postmenopausal symptoms, produces adequate plasma estradiol levels and allows good compliance to treatment.

Sequential use of conjugated estrogens and medroxyprogesterone in the climacteric syndrome: clinical and histological findings.

Seventy-four symptomatic postmenopausal women received conjugated equine estrogens, 0.625 mg daily, alternating 3 wk of treatment with 1 wk free. Medroxyprogesterone acetate, 10 mg daily, was added from day 12 to day 21 of the estrogen therapy. The length of treatment ranged between 36 and 50 mth (media 42.8). This sequential treatment appears to be an effective medication for menopausal women as 86.4% of patients showed a complete regression of symptoms. Its acceptability may be considered good since few side effects and low incidence of abandons (12.2%) were registered. Medroxyprogesterone seems to be a useful agent to counteract the possible cocarcinogenetic effect of conjugated estrogens on account of the high incidence of induced secretory endometrium obtained (92.2%), the reversal of six pretreatment endometrial hyperplasias and the absence of any premalignant endometrial lesion after at least 3 yr of this sequential treatment. The only case of endometrial cancer registered does not jeopardize this conclusion as was observed in a women who took medroxyprogesterone very irregularly.

Metastasis vaginal como sintoma unico de presentacion de un hipernefroma. / Vaginal metastasis as single symptom of pressentation of a hypernephroma

Se presenta un caso de hipernefroma cuyo sintoma de presentacion fue una metastasis vaginal. Se efectua una revision de la casuistica mundial que alcanza a 60 casos y se realizan consideraciones sobre su origen, diseminacion, sintomatologia y tratamientos. Se destaca la necesidad de sospechar la existencia de un cancer renal en toda lesion vaginal cuya histologia sea la de un adenocarcinoma y de que las posibilidades de curacion son escasas pero ciertas si la metastasis vaginal es unica

Metastasis vaginal como sintoma unico de presentacion de un hipernefroma. / Vaginal metastasis as single symptom of pressentation of a hypernephroma

Se presenta un caso de hipernefroma cuyo sintoma de presentacion fue una metastasis vaginal. Se efectua una revision de la casuistica mundial que alcanza a 60 casos y se realizan consideraciones sobre su origen, diseminacion, sintomatologia y tratamientos. Se destaca la necesidad de sospechar la existencia de un cancer renal en toda lesion vaginal cuya histologia sea la de un adenocarcinoma y de que las posibilidades de curacion son escasas pero ciertas si la metastasis vaginal es unica

[Use of a new steroid (Org OD 14) in the climacteric syndrome]. / Uso de un nuevo esteroide (Org OD 14) en el síndrome climatérico.

A double-blind study was carried out in 60 women with climacteric symptoms: 30 women were given Org OD 14 (2.5 mg) and 30 were given a placebo to be taken daily for six weeks. The effects of the medication on the climacteric symptoms, the subjective sensations, the plasma FSH levels and endometrial histology were studied. In the treated group compared with the control group the relief or improvement of the following climacteric symptoms were recorded: perspiration, palpitations, irritability and backache. A favourable effect on the subjective sensations was noted in both groups, although no significant difference for the group which received Org OD 14 was found. At the end of the treatment with Org OD 14, the FSH levels were found to be greatly reduced in comparison with the basal values; this, however, was not the case with the placebo group. With regard to endometrial histology, no sign of hyperplasia was found in any of the patients. No relevant side effects or symptoms of estrogenic or androgenic stimulation were recorded. For the climacteric patient needing estrogen therapy, it can be concluded that Org OD 14 is an effective and innocuous medication in the doses used.

Bromocriptine in the treatment of hyperolactinemic amenorrhea.

Thirty women with secondary amenorrhea and hyperprolactinemia were studied; galactorrhea was present in 25 of them, and 18 were infertile. Serum prolactin (PRL) levels were high in all cases, between 26 and 120 ng/ml. All women were treated with bromocriptine in increasing doses from 2.5 to 5.0 or 7.5 mg daily, according to the response obtained, for 4 months. In 27 patients a PRL determination was performed during treatment; values returned to normal (up to 20 ng/ml) in 23 women and remained high in 4. Galactorrhea disappeared in 21 of 25 women. Ovulatory menses were re-established in 17 patients (56.6%). Seven women became pregnant (38.8%), one of them after bromocriptine and clomiphene were given simultaneously in the same cycle. According to our results and a literature review the following conclusions may be drawn: (1) bromocriptine is a useful therapeutic tool for re-establishing menstruation and inducing ovulation in patients with the hyperprolactinemic-amenorrhea syndrome; (2) the association of bromocriptine and clomiphene could be the next step in the treatment of patients who fail to ovulate with bromocriptine alone.

Plasma levels of norepinephrine during the periovulatory period in normal women. Further studies.

Eleven normally cycling women in whom laparotomy was indicated for benign gynecologic pathology were studied. Surgery was performed on day 0 (expected day of ovulation). Blood samples were drawn daily from day -8 to day -4, and every 8 hours from day -3 to day +2; estradiol (E2), progesterone (P), norepinephrine (NE), and LH were determined by RIA. Ovulation was certified by ovarian visualization and biopsy during laparotomy. In nine ovulatory patients mean E2 peak was found 48 hours before LH peak. Mean NE levels showed minimal variations until 48 hours before LH peak; 8 hours after E2 peak mean NE values increased significantly, fell 8 hours later, and rose immediately again, reaching maximal levels 24 hours after E2 peak. These values remained high until 16 hours before the LH peak and decreased gradually, thereafter reaching basal levels 32 hours after LH peak. Two anovulatory patients showed an atypical pattern of ovarian steroids and LH secretion and NE showed large variations without any correlation with estradiol or LH levels. This study confirms previous findings in women and experimental work in animals regarding the existence of a noradrenergic trigger mechanism to the LH ovulatory discharge.

Plasma levels of norepinephrine (NE) during the periovulatory period and after LH-RH stimulation in women.

In three normally cycling women studied daily from day 10 to 17 of the menstrual cycle, the levels of circulating norepinephrine showed a sharp rise preceding or concomitantly with the ovulatory LH surge. In two patients the norepinephrine peak took place 24 hr. previously to the LH rise and in the third one it occurred simultaneously. The simultaneous determination of ovarian hormones and norepinephrine showed no temporal correlation between this catecholamine and either estradiol or progesterone. On the other hand, after a single intravenous 100 mug dose of LH-RH, a significant rise in plasma norepinephrine, preceding the LH peak, was found in the four patients studied. The determination of norepinephrine at 3 minute intervals beginning one minute after LH-RH injection showed a significant rise in the amine levels ranging from 5 to 10 times in respect to basal values between 1 and 6 minutes after LH-RH stimulation. In these patients a second peak of norepinephrine occurred simultaneously with the maximal response of LH, which rose to peak levels after 18 minutes in one patient and after 24 minutes in the other. These findings are discussed with respect to the origin and role of increased amounts of plasma norepinephrine related to the LH surge.

[Treatment of the anovulatory sterility with LH-RH (author's transl)]. / Tratmiento de la esterilidad anovulatoria con LH-RH

Thirthy one infertile women with different forms of anovulation were treated with LH-RH on various schemes of application: continuous intravenous (i.v.) infusion, intramuscular (i.m.) unique injection, continuous i.v. infusión plus i.m. unique injection, repeated i.v. injection, repeated i.m. injection and estrogens plus unique i.m. injection. On 46 cycles treated, ovulation was obtained in 18 (39.1%), 13 patients ovulated at least one cycle (41.8%) and six became pregnant (19.3%) three during the treatment and three during the first cycle post-treatment. The best results were obtained (63.2%) of ovulation) with the repeated i.v. injection scheme. Though the results obtained with LH-RH in relation to pregnancies, are lower than those obtained with other therapies of anovulation, the fact that we have been sucessful in cases on which other therapies of anovulation had been unsuccessful, the report up to now of only one case of mild ovary hyperestimulation, and the recent development of LH-RH analogs of more powerful and longer action, justifies the continuing of therpeutic assays with this hormone as to find the most effective scheme to induce ovulation.