Relationship of Ethinylestradiol/Drospirenone Prescription on Work Productivity and Activity Impairment Among Women With Menstruation-Related Symptoms: A Multicenter Prospective Observational Study.

OBJECTIVE: The aim of the study is to examine changes in work productivity and daily activity impairment among women by starting ethinylestradiol (EE)/drospirenone (DRSP) for perimenstrual symptoms. METHODS: Participants were women who were newly prescribed EE/DRSP at 25 gynecological clinics in Japan. Eligible participants recorded daily intake of EE/DRSP and the Work Productivity Activity Impairment Questionnaire General Health every 2 weeks for 3 months by smartphone app. A linear mixed-effects model was used to see changes in work productivity impairment and activity impairment relative to baseline. RESULTS: A total of 222 participants were eligible. Work productivity impairment recovered by 20.0% (95% confidence interval, 14.1%-26.0%) at 1 m and maintained for 2 months. Activity impairment recovered by 20.1% (95% confidence interval, 15.5%-24.7%) at 1 m and thereafter. CONCLUSIONS: Improvements in work productivity and daily activities were observed at 1 m after EE/DRSP initiation, with a sustained effect thereafter.

Co-medication and potential drug interactions among patients with epilepsy.

PURPOSE: This study aimed to analyze the extent of co-medication and to assess potential interactions between antiepileptic drugs (AEDs) and other drugs among patients with epilepsy. METHODS: We studied 663 consecutive patients with epilepsy seen in tertiary outpatient clinic. Data on epilepsy and current treatment with AED(s) were collected from structured interview and medical records. Other medications used regularly were classified according to the Anatomical Therapeutic Chemical classification system. Possible drug interactions between AEDs and other drugs were analyzed with the use of IBM Micromedex® database. RESULTS: Studied sample included 395 women; 54.5% of subjects were on monotherapy. Enzyme-inducing AED(s) were used by 127 patients (19.2%). Among 265 patients who used medications other than AEDs (40.0% of all subjects), potential major and moderate interactions between AEDs and other drugs were found in 80 patients (30.1%). Most prevalent major interactions included: ethinylestradiol/estradiol - valproate/oxcarbazepine/carbamazepine, sertraline-carbamazepine, and simvastatin-carbamazepine. A total number of currently used medications (OR = 1.26 [1.07-1.48] per one additional medication; p = 0.005) and the use of enzyme-inducing AEDs (OR = 2.78 [1.51-5.12]; p < 0.001) were independent predictors of interactions between AEDs and other drugs. CONCLUSIONS: Co-medication is common (40%) among patients with epilepsy. Potential major or moderate interactions between AED(s) and other drugs are noted in 30.1% of patients exposed to at least one medication other than AED (12.1% of the entire cohort). The risk of potential interactions increases with the number of medications used chronically and with the use of hepatic enzyme-inducing AEDs.

Proandrogenic and Antiandrogenic Progestins in Transgender Youth: Differential Effects on Body Composition and Bone Metabolism.

Context: Progestins can be used to attenuate endogenous hormonal effects in late-pubertal transgender (trans) adolescents (Tanner stage B4/5 and G4/5). Currently, no data are available on the effects of progestins on the development of bone mass or body composition in trans youth. Objective: To study prospectively the evolution of body composition and bone mass in late-pubertal trans adolescents using the proandrogenic or antiandrogenic progestins lynestrenol (L) and cyproterone acetate (CA), respectively. Design and Outcome Measurements: Forty-four trans boys (Tanner B4/5) and 21 trans girls (Tanner G4/5) were treated with L or CA for 11.6 (4 to 40) and 10.6 (5 to 31) months, respectively. Anthropometry, grip strength, body composition, and bone mass, size, and density were determined by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography before the start of progestin and before addition of cross-sex hormones. Results: Using L, lean mass [+3.2 kg (8.6%)] and grip strength [+3 kg (10.6%)] significantly increased, which coincided with a more masculine body shape in trans boys. Trans girls showed loss of lean mass [-2.2 kg (4.7%)], gain of fat mass [+1.5 kg (9.4%)], and decreased grip strength Z scores. CA limited normal bone expansion and impeded pubertal bone mass accrual, mostly at the lumbar spine [Z score: -0.765 to -1.145 (P = 0.002)]. L did not affect physiological bone development. Conclusion: Proandrogenic and antiandrogenic progestins induce body composition changes in line with the desired appearance within 1 year of treatment. Bone health, especially at the lumbar spine, is of concern in trans girls, as bone mass accrual is severely affected by androgen suppressive therapy.

COMPARISONS BETWEEN THE NON-PROLIFERATIVE AND PROLIFERATIVE THERAPY IN FIBROCYSTIC MASTOSIS.

AIM: Fibrocystic mastosis (FCM) is the most frequent benign breast lesion. Most treatments for fibrocystic mastosis are: hormonl, with beneficial results and non-hormonal, with fluctuating results. MATERIAL AND METHODS: A number of 210 cases were studied, which were divided into 7 groups. The study lasted for 9 months and it was carried out on the basis of a personal examination sheet. The following were monitored: age groups, mastodynia, reducing breast nodules, a significant reduction in the volume of the mastosic cysts, reducion of the fibrous tissue, medication tolerance. RESULTS: Mastodynia has declined by 90% in the cases treated with Tamoxifen and Danazol, by 70% in the case of Lynestrenol and Bromocriptine, by 50% in the 15 patients who were given Utrogestan. Knowing the advantages and disadvantages of drugs (contraindications, side effects), age category, breast pain reduction, antiproliferative activity, tolerability, relapse allow us to assess the benefit-risk. Even in those circumstances that remained incompletely clarified for objective reasons, related to the inaccurate/incorrect reporting by the patients, there is a significant difference (p < 0.05) between the frequency of relapses following the treatment with Tamoxifen and the other categories of drugs who were administered. CONCLUSIONS: Our study shows that in the groups that were administered Logest, Utrogestan and Bromocriptine, only antalgic effects were achieved (disappearance or only decrease of mastodynia) and no anti-proliferative effects were obtained. Basically, hormone treatment should be made based on a histopathological examination.

[Endometrial cancer in a 25-year-old patient. Case study]. / Rak blony sluzowej macicy u 25-letniej pacjentki. Opis przypadku.

Endometrial cancer is one of the most frequently diagnosed malignant neoplasms among women. In Poland, it is in the fourth place in terms of incidence. The highest morbidity concerns women aged 50-70 years, however it may also appear in women in their reproductive period. Endometrial cancer concerns about 3% of premenopausal women. We present a case of a 25-year-old patient who underwent endometrial curettage because of irregular menstrual bleeding for the last 5 months. Histopathology revealed endometrial cancer. We attempted to apply a conservative treatment. During the next 6 months the patient was treated with lynestrenol. After one month of hormonal therapy endometrial curettage was repeated. In histopathology endometrial tissues corresponding to the hormonal treatment were found. After 6 months of treatment hysteroscopy with endometrial biopsy followed by endometrial curettage, were performed. Hormonal treatment resulted in disease regression. About 5 months after successful treatment the patient conceived spontaneously. One year after she gave birth to her first child, she conceived spontaneously once more. Both children were born vaginally. In selected cases of atypical hyperplasia and early endometrial cancer in young women the attempt of hormonal treatment is acceptable.

[Ectopia of cervix of the uterus and hormonal contraception].

The aim of the study was the investigation of impact of different hormonal contraceptive drugs on cervix of uterus of young nullipara women with ectopia. Cytologic smears were examined using Pappanikolau method. Cohort study was carried out by using simple blind method. The data were treated by statistics packet (SPSS). The results displayed correlation between taking the hormonal contraceptives Rigevidon and Marvelon and in transformation of ectopia into micro glandular hyperplasia, which did not occur in taking medicine Exluton. Drug Exluton is recommended for young nullipara women with ectopia to exclude micro glandular hyperplasia. In case of prescribing monophase contraceptives for young nullipara women with ectopia cytological control of endo- and exo-cervix is recommended.

Contraceptive vaginal rings releasing Nestorone and ethinylestradiol: a 1-year dose-finding trial.

In a multicenter 1-year trial of contraceptive vaginal rings (rings) involving 150 women, three dose combinations of the progestin Nestorone (NES) and ethinylestradiol (EE) were compared with respect to effectiveness, safety and acceptability. Mean in vitro drug release rates for the three doses were 150 and 15, 150 and 20 and 200 and 15 microg/day of NES and EE, respectively. Each ring remained in situ for 21 days, removed for 7 days and then reinserted for a total of 13 cycles of use. We studied ring performance with respect to pregnancy and other termination events, adverse events, the extent of ovulation inhibition, serum drug levels and bleeding control. We also assessed the rings' effects on the vagina using a standardized colposcopy procedure. Seventy-two percent of the women completed the 1-year (> or = 350 days) study. In studied cycles, luteal activity (progesterone > or = 10 nmol/L) was noted in 17%, 7% and 12% of subjects with monitored cycles at the 150/15, 150/20 and 200/15 doses, respectively (p = .34). Two pregnancies occurred, both in subjects using the 200/15 microg/day ring. Breakthrough bleeding during ring use averaged about 2 days/year and breakthrough bleeding and spotting averaged about 7 days/year. In the entire trial, only two women discontinued because of bleeding problems. Medical conditions, chiefly vaginal problems, personal reasons and device loss or repeated expulsion were the principal reasons given for study discontinuation. Vaginal and cervical colposcopy, conducted with standardized techniques and standardized interpretations, revealed no elevated event incidence attributable to ring use. Clinical performance and adverse event profiles indicate that each of these 1-year NES/EE rings, used on a 21-day-in and 7-day-out regimen, provided women effective, acceptable and safe long-acting contraception under their own control.

Prospective randomized study comparing the GnRH-agonist leuprorelin acetate and the gestagen lynestrenol in the treatment of severe endometriosis.

Endometriosis is thought to be an ovarian-dependent benign disease that affects up to 12% of women during their reproductive life. For the past ten years the gonadotropin-releasing hormone (GnRH)-agonists have been proved effective and safe drugs in the treatment of endometriosis. Nevertheless, gestagens such as lynestrenol still remain the most often used hormonal drugs for the treatment of this disease. The primary objective of this study was to compare the efficacy of the GnRH-agonist leuprorelin acetate depot (LAD) (Enantone-Gyn) 3.75 mg subcutaneously per month with that of the gestagen lynestrenol (LYN) (Orgametril) 5 mg orally twice per day in women with severe endometriosis, in terms of postoperative revised American Fertility Society (r-AFS) scores I-IV at first-look laparoscopy (score after removal of endometriotic lesions or adhesions) to the r-AFS score after six months' treatment. Secondary objectives were the improvement of clinical symptoms and the side-effect profile. Forty-eight women with postoperative r-AFS scores I-IV were evaluated in an open prospective randomized study between 1996 and 1998. All the participants underwent a first-look laparoscopy with resection of endometriotic lesions and six months' therapy with one of the above mentioned drugs, and a further second-look laparoscopy. The six months' treatment with LAD or LYN led to a significant reduction of the r-AFS score points in both groups. The mean r-AFS score in points for the LAD group after the first-look laparoscopy was 21.8 and was 27.2 for the LYN group. After the medical treatment a mean value of 11.5 points was observed in the LAD group compared with a mean value of 25.5 in the LYN group. This difference was statistically significant (p = 0.000014, Wilcoxon test). The improvement in the symptoms of dysmenorrhea, chronic pelvic pain and dyspareunia was also more pronounced in the LAD-treated group. LAD was more effective than LYN in the suppression of circulating serum 17 beta-estradiol levels after 6 months of treatment (mean 27.7 +/- 9.3 pg/ml versus 42.6 +/- 59.3 pg/ml). All the observed side-effects were deemed tolerable by the women who participated in this study. As the reduction of the r-AFS score in points was much more pronounced in the LAD group than in the LYN group, GnRH-agonists should therefore be used as first-choice drugs in the treatment of endometriosis. Due to the limited treatment of 6 months' duration of GnRH-agonists, gestagens might be used as second-line drugs for long-term and continuous treatment in the management of endometriosis to maintain the primary beneficial effect of GnRH-agonist treatment in patients who have completed their families.

Leuprorelin depot 3.75 mg versus lynestrenol in the preoperative treatment of symptomatic uterine myomas: a multicentre randomised trial.

OBJECTIVES: To compare the effect of the gonadotrophin-releasing hormone agonist leuprorelin and progestin lynestrenol, given prior to surgical treatment of symptomatic uterine myomas, on the pre-operative symptoms, tolerance, and operative blood loss. STUDY DESIGN: Fifty-six women were randomly selected to receive, during 16 weeks, either monthly subcutaneous injections of leuprorelin 3.75 mg sustained release (n=33) or lynestrenol 5 mg two tabs per day (5th to the 25th menstrual cycle) (n=23). RESULTS: Intent-to-treat analysis of the main efficacy criterion, namely ultrasonographic reduction of myoma(s) diameter, showed a significant difference in favour of leuprorelin (P=0.02) with a mean decrease of 26.5+/-4.5% (n=29) as opposed to 7.3+/-5% in the lynestrenol group (n=17). Clinical improvement was satisfactory in both groups. Hematocrit decrease between the preoperative value and the value measured 48 h postoperatively was significantly lower in the leuprorelin group than in the lynestrenol one (P=0.02) (for hemoglobin: P=0.07). CONCLUSION: Leuprorelin was more effective than lynestrenol because of its more intense antigonadotropic activity. The tolerance was good, reflecting each drug mechanism of action.

Tenoxicam versus lynestrenol-ethinyl estradiol treatment of dysfunctional uterine bleeding cases during adolescence.

BACKGROUND: The purpose of this study was to compare the effectiveness of tenoxicam versus lynestrenol-ethinyl estradiol (L-EE) in the treatment of severe cases of dysfunctional uterine bleeding (DUB) during adolescence. METHODS: Forty-eight patients with objective DUB completed a randomized comparative trial of treatment with tenoxicam (20 mg daily, n = 23) or L-EE (1 tablet containing 0.05 mg + 2.5 mg, respectively, 3 times daily, n = 25). Treatment was given during menorrhagia until bleeding ceased. Mean age of the patients was 13.74 +/- 2.1 years (range, 11-18 years). RESULTS: A significantly higher level of hematocrit (35.9% v 32.6%, t = 2.1, P = 0.0217) and hemoglobin (11.5 v 10.4 g%, t = 1.7, P = 0.0495), and significantly less hospitalization (5.75 v 8.33 days, t = 2.45, P = 0.0106) was seen in the tenoxicam group in comparison to L-EE group after completion of the treatment. Three patients were submitted to curettage and seven to transfusion in the group receiving L-EE, but no patients in the tenoxicam group required these procedures. CONCLUSIONS: Tenoxicam is considered an effective medication for the management of DUB during adolescence.

Alopécia androgenética feminina: estudo hormonal e avaliaçäo do tratamento com antiandrógenos / Female androgenetic alopecia: hormonal study and evaluation of antiandrogen treatment

O objetivo deste trabalho foi avaliar a eficácia do tratamento com antiandrógenos em mulheres com alopécia androgenética (AA). Realizamos dosagens de testosterona total (T), testosterona livre (TL), sulfato de deidroepiandrosterona (DHEA-S), androstenediona (A), proteína ligadora dos hormônios sexuais (SHBG), androstanediol glucuronídeo (3alpha-diol G), TSH, anticorpo antimicrossomal e as relaçöes T/SHBG (x100) e 3alpha-diol G/SHBG em 30 mulheres com AA, idades entre 14 e 46 anos, e comparamos com grupo controle, constituído por 11 mulheres, idades entre 16 e 27 anos. Quatro pacientes tiveram diagnóstico de doença endócrina: hipotireoidismo primário (n=2), síndrome dos ovários policísticos e hirsutismo idiopático. Nas demais 26 pacientes, a relaçäo 3alpha-diol G/SHBG foi maior (p<0,05), sem diferença na concentraçäo dos androgênios, quando comparamos com o grupo controle. Sete pacientes utilizaram acetato de ciproterona (50mg/dia) associado com etinilestradiol (AC+E) e cinco pacientes utilizaram espironolactona (100mg/dia) por 6 meses. Houve diminuiçao estatisticamente significativa nas dosagens de 3alpha-diol G, SHBG e da relaçäo T/SHBG somente nas pacientes que utilizaram AC+E. Todas as pacientes relataram melhora da queda do cabelo. Observamos, através do tricograma, um aumento estatisticamente significativo dos pêlos anágenos nas pacientes que utilizaram AC e espironolactona (p<0,05) e diminuiçao de pêlos anágenos disäo androgênica que ocorre em mulheres geneticamente predispostas. O tratamento com AC+E acarreta uma melhora no perfil hormonal e na análise do tricograma sendo necessário tratamento mais prolongado para que seja observado aumento na quantidade do pêlo.

[Menstruation-associated (catamenial) pneumothorax and catamenial hemoptysis]. / Menstruations-assoziierter (catamenialer) Pneumothorax und catameniale Hämoptyse.

We report on 2 patients with catamenial pneumothorax and one patient with catamenial hemoptysis. The pathogenesis of these diseases is not clear, and intrathoracic endometriosis is often assumed. Catamenial pneumothorax is rare and differs from primary spontaneous pneumothorax in its prevalence in the fourth decade and in mainly multiparous women, its recurrent and almost exclusively right-sided occurrence within 72 hours of the beginning of menstruation, and the generally small size of the pneumothorax. About 5% of women under 50 presenting with primary pneumothorax have catamenial pneumothorax. Prevention of recurrence is difficult, as the recurrence rate is high, treatment duration is potentially long, and residual thoracic pain during menstruation is sometimes seen. The combination of medication (Gn-RH analogues, danazol, possibly hormonal contraceptive drugs or progestagens) with efficient pleurodesis (e.g. thoracoscopic talc application preferentially performed during menstruation) seems so far to be the most efficient, although no controlled studies have yet been performed. Catamenial hemoptysis is very rare and hormonal treatment alone is frequently successful in the long term. In the event of relapse, resection of the implicated endometriotic or angiomatous lesion localized by computed tomography can be performed.

[Enzyme therapy in treatment of mastopathy. A randomized double-blind clinical study]. / Enzymtherapie zur Behandlung der Mastopathie. Eine randomisierte doppelblinde klinische Studie.

In this randomized double-blind clinical study the efficacy of an enzyme preparation (Wobenzym) was compared with hormone therapy (Lynestrenol) in 29 women with mastopathy. There was a significantly greater decrease in number of hardenings of the mammary gland after 2 months of enzyme therapy than Lynestrenol therapy: improvement in the former group was 100%, in the latter group 78.6%. No significant difference was observed regarding the numbers of lumps, or number and size of cysts, sensitivity to touch, feeling of tension, spontaneous pain, and pain on pressure. The efficacy of both medicines is valued as good. Wobenzym therapy was tolerated very well. No side effects appeared at all. Enzyme therapy is an alternative, low-risk therapy for the management of mastopathy, which does not interfere with the already upset hormonal balance of the patients.

Stereometric evaluation of peritoneal endometriosis and endometriotic nodules of the rectovaginal septum.

A computerized morphometrical investigation was performed on endometriotic tissue from the peritoneum (n = 225) and rectovaginal nodules (n = 65) to compare histologically and stereologically the rectovaginal septum endometriotic nodule to peritoneal endometriosis. Mitotic activity, stromal vascularization and the epithelium/stroma ratio were found to be significantly different in peritoneal and rectovaginal endometriosis. The evaluation revealed a major role of glandular epithelium in rectovaginal nodules where the stroma sometimes appeared absent around glandular epithelium. The study demonstrated opposite effects of gonadotrophin-releasing hormone agonists (GnRHa) and lynestrenol on the two lesions. Indeed, in peritoneal endometriosis, after GnRHa therapy, our study demonstrated a lower rate of mitosis and poor stromal vascularization. The same drug was unable to induce the same effects in the nodule although, in contrast, lynestrenol has a strong effect on nodule vascularization. In conclusion, it is suggested that the rectovaginal adenomyotic nodule is a specific disease, different from peritoneal endometriosis. It is not the consequence of 'deep infiltrating' endometriosis but can probably develop from Mullerian rests present in the rectovaginal septum.

[Regression of functional cysts: high dosage ovulation inhibitor and gestagen therapy has no added effect]. / Zur Rückbildung funktioneller Zysten: Hochdosierte Ovulationshemmer und Gestagentherapie ohne zusätzlichen Effekt.

To investigate the need for hormonal treatment in patients with functional ovarian cysts (FOC), the efficacy of this treatment was evaluated in a retrospective and also in a randomised prospective study. By retrospective analyses the resolution of FOC with a mean diameter larger than 2.0 cm at the beginning of a cycle was determined in 113 patients (31.6 +/- 4.6 years). Fifty-seven women received an oral contraceptive (ethinylestradiol 50 micrograms/d for 7 days, ethinylestradiol 50 micrograms and desogestrel 125 micrograms/d for 15 days), the others had no therapy. In a second study 59 patients (32.3 +/- 4.6 years) were randomised to receive a combination of ethinylestradiol 50 micrograms and levonorgestrel 250 micrograms/d for 21 days (Group 1, n = 24), or lynestrenol 10 mg/d continuously (Group 2, n = 14) or a third group (Group 3, n = 21) without treatment. In both studies no differences were found between those patients who had hormonal treatment and those who had not. The prospective study revealed that spontaneously appearing FOC and FOC evolving after ovulation induction during the cycle prior to study enrolment, resolved equally well within 12 weeks independent of contraceptive or gestagen treatment. FOC persisted in only one woman (group 2) who had a surgically proven endometrioma. In conclusion, hormonal treatment does not produce regression of FOC in women of reproductive age.

[Estrogen and progestagen treatment in digestive hemorrhage caused by vascular malformations]. / Tratamiento con estrógenos y progestágenos en la hemorragia digestiva por malformaciones vasculares.

The efficacy of an association of estrogens and progestagens in the treatment of gastrointestinal bleeding by angiodysplasia was analyzed. Thirty-three patients with gastrointestinal bleeding due to vascular malformations were admitted from January 1986 to December 1993. Fifteen of the 33 patients were submitted to surgical or endoscopic treatment. The remaining 18 patients underwent daily oral treatment with a combination of estrogens-progestagens containing 2.5 mg of lynestrenol and 0.075 mg of mestranol. One patient presented a venous thrombosis leading to suppression of treatment at one month of initiation. The 17 remaining patients were treated for a mean of 22 +/- 4 months (range: 3-60). During treatment 13 of the 17 patients (76%) did not present evidence of hemorrhage. Likewise, the number of hemorrhagic episodes per year decreased from 4.4 +/- 1.2 prior to treatment to 0.7 +/- 0.5 during treatment (p < 0.05) with transfusional requirements decreasing from 7.9 +/- 2.8 erythrocyte concentrates per year prior to treatment to 1.2 +/- 1.0 during treatment (p < 0.05). In conclusion, the combined treatment with estrogens and progestagens prevents recurrence of gastrointestinal bleeding by angiodysplasia.

Antiandrogen treatment with spironolactone and linestrenol decreases bone mineral density in eumenorrhoeic women with androgen excess.

Increased bone mineral density (BMD) has been reported in young women with androgen excess. To determine whether antiandrogen treatment in young women with androgen excess reduces BMD in these patients, the authors measured BMD before and a year after the beginning of antiandrogen therapy with spironolactone and linestrenol in 17 consecutive androgenized patients (median age 22 years). After a year's treatment BMD declined in 15 out of 17 patients, the mean decrease--0.032 g/cm2 (95% CI of the difference 0.016-0.048)--being highly significant (p < 0.001). Androstenedione decrease was the only hormonal variable significantly correlating with BMD decrease (r = 0.5; p = 0.037) according to simple linear regression. A decrease of BMD might become a key factor in deciding about the duration of antiandrogen treatment with spironolactone in functional hyperandrogenemia.

[Lynestrenol and allylestrenol in the therapy of postmenopausal hot flushes]. / Lynestrenol a allylestrenol v lécbe postmenopauzálních návalu horka.

In a parallel randomized placebo controlled clinical trial the authors tested two synthetic gestagens--allylestrenol and lynestrenol--in the treatment of postmenopausal flushes. Both preparations were administered during a six-week period in rapidly declining doses. Allylestrenol was administered in initial doses of 30 mg/d, after five days the doses were reduced so that after 15 days a daily dose of 5 mg was reached. The initial dose of lynestrenol was 10 mg/d with a similar gradual decline to 1.25 mg per day. The trial comprised 42 women with menopausal flushes after a natural or artificial menopause (castration). Both preparations improved the subjective condition of the patients and reduced the gonadotropic production significantly better than placebo (p < 0.05). Subjective relief after lynestrenol was recorded after the second week of therapy, in allylestrenol only after the sixth week when the effects of the two preparations were equal and significantly better than after placebo. Suppression of gonadotropin production was similar after both preparation but with a more rapid onset after lynestrenol and a more prolonged effect after allylestrenol even after significant reduction of the doses. No serious undesirable effects were recorded, no changes in indicators of liver functions or serum lipids incl. the HDL/LDL ratio. Endometrial bleeding after administration of hormones was not more frequent than after placebo. In the discussion the authors analyze some aspect of treatment of the climacteric syndrome by means of these hormones. Allylestrenol in particular is an interesting gestagen due to its inherent oestrogenic effect in the absence of an androgenic effect.

Lynestrenol induced therapeutic amenorrhea: effects of dose reduction on serum sex-hormones and lipids.

The effect of reducing the dose of peroral lynestrenol by half on serum sex-hormone, lipid and lipoprotein status was studied in 21 mentally retarded women with therapeutic amenorrhea (TA). They had previously received 5 or 10 mg peroral lynestrenol daily for periods ranging from 32 to 196 months. Dose halving of lynestrenol resulted in an increase in serum total testosterone (T) by 16% (p less than 0.05), sex-hormone binding globulin (SHBG) by 39% (p less than 0.01) and high-density lipoprotein cholesterol (HDL-C) by 28% (p less than 0.001). Both the mean serum total and free concentrations of norethisterone (NET and fNET) decreased by 60% (p less than 0.001). The serum concentrations of 17-beta-estradiol (E2), its free fractions (fE2) and free T (fT) were not significantly altered. Significant correlations were observed between the change in HDL-C and the change in T (r = 0.45, p less than 0.05), between the change in SHBG and the change in T (r = 0.62, p less than 0.01), fT (r = 0.43, p less than 0.05) and E2 (r = 0.51, p less than 0.05). The elevation of HDL-C was probably caused by the reduced serum NET concentrations. This also resulted in an increase in serum SHBG concentration, which is regarded as an indicator of the overall estrogen/androgen ratio.

Double-blind trial of promegestone (R 5020) and lynestrenol in the treatment of benign breast disease.

One hundred thirty-two women between the ages of 19 and 50, with various forms of benign breast diseases received 1 mg promegestone, or 0.5 mg promegestone, or 10 mg lynestrenol daily (double-blind), for 15 days per cycle, during three cycles. The groups were identical before treatment, with the exception of a longer history of mastodynia and mastopathies in the 1 mg promegestone group than in the lynestrenol group (P = 0.04) and a greater proportion of mastosis zones in the lynestrenol group as compared to the 0.500 mg promegestone group (P = 0.05). The effectiveness of lynestrenol both in terms of symptomatology (evaluated as good or excellent in 66.6% of the cases) and of clinical observations (evaluated as good or excellent in 59% of the cases) is not significantly different statistically from that of promegestone at 1 mg, whose effectiveness on symptomatology was good or excellent in 65.9% and 57.1% of the cases, respectively, or from that of promegestone at 0.5 mg/day (with 65% and 51.3% effectiveness, respectively). Clinical tolerance was rated good or excellent for 73.9% of the women on 1 mg promegestone and for 59.5% of the women on 0.500 mg promegestone, compared to 66.7% of the women on lynestrenol. No statistically significant difference was observed, neither between lynestrenol and promegestone 1 mg nor between lynestrenol and promegestone 0.5 mg. This study shows a clear improvement in functional and physical signs in patients treated with promegestone. Promegestone's efficacy is close to that of lynestrenol, a nonsteroidal progestin.2+ off