Comparison of change in body weight between contraception containing 30-µg ethinylestradiol/2-mg chlormadinone acetate or 30-µg ethinylestradiol/3-mg drospirenone: a randomised controlled trial.

Objectives: The aim of this study was to compare changes in body weight in women using a combined oral contraceptive (COC) consisting of 30-µg ethinylestradiol (EE) and 2-mg chlormadinone acetate (CMA) or a COC consisting of 30-µg EE and 3-mg drospirenone (DRSP).Methods: This randomised double-blind controlled trial (ClinicalTrials.gov NCT01608698) was conducted at a university hospital-based clinic in Thailand between June 2012 and September 2015. A total of 102 women were enrolled in the study, 99 of whom were randomised to EE/CMA (n = 45) or EE/DRSP (n = 54). Each participant was treated for six cycles. Body weight and other parameters as well as side effects were recorded at baseline and at the end of the third and sixth cycles of treatment.Results: A significant difference was observed in mean body weight change between the EE/CMA and EE/DRSP groups from both baseline to third cycle (0.51 ± 1.36 kg vs -0.43 ± 1.56 kg; p = .003) and baseline to sixth cycle (1.00 ± 1.84 kg vs -0.20 ± 2.23 kg; p = .013). The mean difference in body mass index and waist circumference had a similar trend to that of the mean difference in body weight. There was no significant difference in side effects between groups.Conclusion: A COC containing 30-µg EE/3-mg DRSP tended to confer a significantly more favourable change in body weight over a 6-month period compared with a COC containing 30-µg EE/2-mg CMA, which was associated with an increase in body weight.

Progestin-associated shift of meningioma mutational landscape.

Background: Meningiomas are the most common primary tumor of the central nervous system. The relationship between meningioma and progestins is frequently mentioned but has not been elucidated. Patients and methods: We identified 40 female patients operated for a meningioma after long-term progestin therapy and performed targeted next generation sequencing to decipher the mutational landscape of hormone-related meningiomas. A published cohort of 530 meningiomas in women was used as a reference population. Results: Compared with the control population of meningiomas in women, progestin-associated meningiomas were more frequently multiple meningiomas [19/40 (48%) versus 25/530 (5%), P < 10-12] and located at the skull base [46/72 (64%) versus 241/481 (50%), P = 0.03]. We found a higher frequency of PIK3CA mutations [14/40 (35%) versus 18/530 (3%), P < 10-8] and TRAF7 mutations [16/40 (40%) versus 140/530 (26%), P < 0.001] and a lower frequency of NF2-related tumors compared with the control population of meningiomas [3/40 (7.5%) versus 169/530 (32%), P < 0.001]. Conclusion: This shift in mutational landscape indicates the vulnerability of certain meningeal cells and mutations to hormone-induced tumorigenesis. While the relationship between PIK3CA mutation frequency and hormone-related cancers such as breast and endometrial cancer is well-known, this hormonally induced mutational shift is a unique feature in molecular oncology.

[Transient, secondary hypoadrenocorticism after treatment with delmadinone acetate (Tardastrex®) in a two year old male dog]. / Transienter, sekundärer Hypoadrenokortizismus nach Behandlung mit Delmadinonacetat (Tardastrex®) bei einem zwei Jahre alten Rüden.

INTRODUCTION: A two year old male Labrador Retriever was treated with delmadinone acetate because of benign prostatic hyperplasia. Four days after the injection the dog showed gastrointestinal signs and a progressive lethargy. In the hospital for small animals of the Justus-Liebig-University of Gießen an ACTH stimulation test was done and a secondary hypoadrenocorticism was diagnosed. The dog was treated with prednisolone in physiological dose for 14 weeks after the injection. The clinical symptoms stopped immediately. A new ACTH stimulation test some weeks later showed a completely normal adrenal function.

Modification of body composition and metabolism during oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol.

AIM: To observe the influence on metabolism and body composition of two oral contraceptives containing non-androgenic progestins in association with estradiol or ethinyl estradiol (EE). STUDY DESIGN: Women on hormonal contraception with estradiol valerate (E2V)/dienogest (DNG) in a quadriphasic regimen (n = 16) or 30 µg EE/2 mg chlormadinone acetate (CMA) (n = 16) in a monophasic regimen were evaluated at the third cycle for modifications in lipoproteins, apoproteins and homeostatic model assessment for insulin resistance (HOMA-IR), and at the sixth cycle for body composition and the markers of bone turnover osteocalcin and C-telopeptide X. RESULTS: During E2V/DNG lipoprotein, apoproteins and HOMA-IR remained stable. During EE/CMA, total-cholesterol (p = 0.003), high-density lipoprotein (HDL)-cholesterol (p = 0.001), triglycerides (p = 0.003) Apoprotein-A1 (Apo-A1; p = 0.001) and Apo B (p = 0.04) increased, low-density lipoprotein/HDL (p = 0.039) decreased and total-cholesterol/HDL and Apoprotein-B/Apo-A1 ratio did not vary. HOMA-IR slightly increased from 1.33 ± 0.87 to 1.95 ± 0.88 (p = 0.005). There was a reduction of markers of bone metabolism in both groups with no modification of body composition. CONCLUSIONS: Administration of E2V/DNG does not influence lipid and glucose metabolism, while mixed effect are exerted by EE/CMA. Both preparations reduce bone metabolism without influencing short-term effect on body composition.

Prospective study of fertility-sparing treatment with chlormadinone acetate for endometrial carcinoma and atypical hyperplasia in young women.

OBJECTIVE: To confirm that the efficiency of the use of chlormadinone acetate for 6 months to obtain remission of atypical hyperplasia or endometrial carcinoma is comparable to that of the use of other fertility-sparing treatments. METHOD: The present study is based on the PREFERE prospective registry. All the patients received 3 or 6 months of chlormadinone acetate and were evaluated by hysteroscopic resection and pipelle sampling every 3 months. RESULTS: Ninety-four patients were included. Seventy-nine patients achieved complete remission at 6 months (84%). No patients stopped treatment because of a lack of tolerance. Twenty-four per cent of the patients achieved a live birth. CONCLUSION: Chlormadinone acetate is an effective and well-tolerated fertility-sparing treatment. Its benefits over other progestins are its tolerability, and its absence of contraindications, which make it a good choice for patients with thromboembolism and high vascular risk.

Extended cycles with the combined oral contraceptive chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg: pooled analysis of data from three large-scale, non-interventional, observational studies.

BACKGROUND AND OBJECTIVE: The prescribing of extended regimens of oral contraceptives (OCs) is increasing in routine gynaecological practice as a means of reducing the number of annual menstrual bleeds. Typically, this involves taking one pill per day for, say, 84 days continuously (4×21 days), followed by a 7-day pill-free interval. Low-dose OCs are suitable for extended use, and many gynaecologists in Germany prescribe the combination of chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg (CMA 2 mg/EE 0.03 mg). The aim of the current study was to assess the risks and benefits of CMA 2 mg/EE 0.03 mg in extended regimens, using pooled data from observational studies. METHODS: This pooled analysis of three large-scale, non-interventional, observational studies assessed the results in women receiving Belara® (CMA 2 mg/EE 0.03 mg) according to an extended regimen compared with conventional regimens documented in the summary of product characteristics. RESULTS: A total of 625 women were identified as extended-regimen users (mean±SD age 24.9±9.0 years). Extended-cycle use was associated with decreases in skin problems, dysmenorrhoea symptoms (as shown by reductions in analgesic use; absence from school, university, or work; and restrictions in leisure and sporting activities), cycle-dependent symptoms (e.g. headache/migraine, breast tenderness), withdrawal bleeding, bleeding duration and reduced libido. Mean bodyweight remained almost constant over 6 months. Only nine adverse drug reactions, none severe, were reported in eight women (1.3%). CONCLUSION: This pooled analysis confirms that extended regimens of CMA 2 mg/EE 0.03 mg reduce cycle-related complaints and are very well tolerated.

[Hemicentral retinal artery occlusion due to oral contraceptives]. / Hemizentralarterienverschluss bei Einnahme der "Pille"--Mitteilungen über Komplikationen von Kontrazeptiva.

BACKGROUND: Low-dose oral contraceptives can still cause thromboembolic disorders with serious neurologic or ocular disabilities. PATIENT: A 22-year-old woman having used oral contraceptives for several months noticed sudden painless visual loss in her left eye. One tablet of her contraceptive contained ethinylestradiol (0.03 mg) and chlormadinonacetate (2 mg). RESULT: Because of the lower left eye visual field defect, the patient could only read with her right eye. She presented complete left inferior hemianopia, indicating a hemicentral retinal artery obstruction. Visual acuity in both eyes was 20 / 20. The left fundus revealed a distinct retinal edema in the area superior to the optic disc and macula due to vascular disturbances of the superior temporal superior and superior nasal retinal arteries. The right eye was normal. Fluorescein angiography revealed recanalized arteries in the superior retinal area with conspiciously early dye filling as a paradoxical sign. Doppler sonography of the neck and orbital arteries and transesophageal echocardiography (TEE) findings were inconspicious. However, blood examination revealed an elevated thrombin-antithrombin complex and reduced free protein S. CONCLUSION: Coagulopathy can be a side effect of oral contraceptives. Even nowadays, women taking contraceptives risk the danger of vascular occlusions especially if the women suffers from arterial hypertension, diabetes mellitus, have a coagulation anomaly, or if she is a chronic smoker. Before treatment with oral contraceptives commences, a thorough medical examination is necessary. If the family history reveals prominent cardiovascular risk factors, testing for thrombophilia is recommended. Even nowadays, patients should be warned of the risk of visual field defects as a potential side-effect associated with oral contraceptives.

Preliminary report of patients with meningiomas exposed to Cyproterone Acetate, Nomegestrol Acetate and Chlormadinone Acetate - Monocentric ongoing study on progestin related meningiomas.

INTRODUCTION: The relationship between meningioma and progestins has not been elucidated. Meningioma regression after acetate cyproterone (CA) withdrawal has been reported. Our purpose was to evaluate the meningioma evolution after withdrawal of progestins in patients who underwent long-term exposure to CA, nomegestrol acetate (NA), chlormadinone acetate (ChlA). METHODS: Our study retrospectively included 69 patients with intracranial meningioma and exposed to one of these 3 progestins between December 2006 and March 2019. In each patient, clinico-radiological (MRI) follow-up was performed every 6 months after diagnosis and treatment withdrawal recommendation. Statistical analyses were applied to compare tumor location and respect of prescription rules between the 3 groups. RESULTS: The mean hormonal exposure was 16 years in CA group (n = 46), 16 years in NA group (n = 12) and 9.7 years in ChlA group (n = 11). A higher rate of "out of label" use was observed in the CA group (p = 0.003). Multiple meningiomas were demonstrated in more than 60% of cases in each group. Anterior skull base location was noted in 60.5% of cases in CA group, 25% of cases in NA group and 36.7% of cases in ChlA group (p = 0.05). Incomplete tumor regression was recorded in 11 cases of CA group and in 2 cases of ChlA group. CONCLUSION: In CA group, our results suggest a strong relationship between this treatment and development of intracranial meningioma. In presence of voluminous asymptomatic meningioma, treatment can be delayed due to the potential regression after withdrawal. On the contrary in NA and ChlA groups, further studies are needed.

Six-month evaluation of the benefits of the low-dose combined oral contraceptive chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg in young women: results of the prospective, observational, non-interventional, multicentre TeeNIS study.

BACKGROUND: In clinical trials and non-interventional studies encompassing > 50,000 women, the monophasic, low-dose combined oral contraceptive (OC) chlormadinone acetate 2 mg/ethinylestradiol 0.03 mg (CMA/EE) has been shown to have various non-contraceptive benefits, as well as contraceptive efficacy and good tolerability. However, there is a paucity of data on use of this OC in young women. OBJECTIVE: To investigate the relevance of, and changes in, cycle disorders, dysmenorrhoea and skin problems in addition to the efficacy and tolerability of CMA/EE in young women. METHODS: In this prospective, observational, non-interventional, multicentre study (TeeNIS [Teenager in Non-Interventional Study 2 mg CMA/0.03 mg EE]), young women (< or =20 years of age) were administered CMA/EE (Belara) once daily for 21 days (one blister strip), followed by either a 7-day pill-free interval (conventional cycle regimen; 89.3%) or a pill-free interval after two blister strips or more (extended cycle regimen; 3.7%), over a 6-month treatment period. Data on the mode of administration were missing for 7.1% of patients. The study included a safety population of 7462 patients (the efficacy population consisted of 6885 patients) from 886 gynaecological centres throughout Germany. RESULTS: Compared with baseline, CMA/EE intake resulted in significant reductions in the numbers of patients with cycle disorders, i.e. spotting (-46%), breakthrough bleeding (-64%), heavy bleeding (-95%) and absence of any bleeding (secondary amenorrhoea; -76%) [all p < or = 0.001], and with dysmenorrhoea (-56%) [p < or = 0.001]. Similarly, there was a significant decrease in the number of patients who used analgesics (-75%), had dysmenorrhoea-associated symptoms (back pain [-69%], headache [-70%], nausea/vomiting [-85%], diarrhoea [-80%], mood swings [-75%] or absence from school/job due to dysmenorrhoea [-92%]), or were restricted in their leisure/sporting activities because of dysmenorrhoea (-83%) [all p < or = 0.001]. Another major benefit of CMA/EE was a significant reduction in the number of patients with skin problems (acne and acne-prone skin) [-55%; p < or = 0.001]. In parallel, the number of patients who needed dermatological treatment (-67%; p < or = 0.001) and concealer cosmetics (-55%; p < or = 0.001) was significantly reduced, and significantly fewer patients felt that their self-esteem was restricted due to skin problems (-67%; p < or = 0.001). There were no relevant weight changes during the observation period; mean bodyweight remained virtually constant (mean weight change <1 kg). At final assessment, physicians' expectations were either 'completely fulfilled' or 'exceeded' with regard to cycle stability, regular bleeding, dysmenorrhoea, effects on weight, and skin problems in 78-95% of patients. CMA/EE provided high contraceptive efficacy with an unadjusted Pearl index of 0.25, calculated from 41 601 cycles of exposure; seven out of eight pregnancies were attributable to user failure, thus resulting in an adjusted Pearl index of 0.03. The tolerability of CMA/EE was excellent, with no unexpected adverse effects. CONCLUSIONS: This observational, non-interventional study in young women showed that CMA/EE had a significantly beneficial effect on cycle disorders, dysmenorrhoea and skin disorders, and confirmed the good efficacy and tolerability of this combined OC.

Early onset vulvar Lichen Sclerosus in premenopausal women and oral contraceptives.

OBJECTIVE: For vulvar Lichen sclerosus (LS) immunological factors, genetic predisposition, and decreased 5 alpha-reductase activity have been discussed as aetiological factors. During the last decade an increase of LS in young women has been suspected. Aim of this study was to evaluate data of premenopausal women with early onset LS to find potential risk factors focussing on the use of oral contraceptives. STUDY DESIGN: We retrospectively analyzed the data of 40 premenopausal patients with early onset LS regarding use of oral contraceptives (OCPs), and first occurrence of LS. To compare these data in a case-control study we analyzed a matched control group of 110 healthy women. RESULTS: All our LS patients were using OCPs compared to 73 women (66.4%) in the control group. OCPs with anti-androgenic activity (chlormadinone acetate, cyproterone acetate, dienogest, and drospirenone) were used by 28 (70%) of the LS patients and by 35 (47.9%) of the 73 women using OCPs in the control group. Thus, the odds ratio for early onset LS for women using anti-androgenic OCPs was 2.53 (95% CI: 1.12-5.75). CONCLUSION: Our data suggest that disturbance of the androgen dependent growth of the vulvar skin by OCPs and especially by OCPs with anti-androgenic properties might trigger the early onset of LS in a subgroup of susceptible young women.

Efficacies of osaterone and delmadinone in the treatment of benign prostatic hyperplasia in dogs.

A multicentre randomised clinical trial was performed to compare the therapeutic potential of osaterone acetate with that of delmadinone acetate in the treatment of benign prostatic hyperplasia in dogs. The osaterone was administered orally at 0.25 mg/kg bodyweight once a day for seven days to 73 dogs. The delmadinone was administered by a single intramuscular or subcutaneous injection at 3 mg/kg bodyweight to 69 dogs. During the 180-day trial, the dogs were monitored five times for their clinical signs and prostate volume. The two drugs were similarly effective in reducing the clinical signs and inducing complete clinical remission, and both induced a similar level of minor, mostly transitory adverse effects. Osaterone reduced the volume of the prostate glands of the dogs significantly more quickly than delmadinone.

Switching hormonal contraceptives to a chlormadinone acetate-containing oral contraceptive. The Contraceptive Switch Study.

PURPOSE: This prospective observational noninterventional study aimed at collecting information on changes in cycle control, dysmenorrhea, androgen-related skin conditions and tolerability in a large cohort of women who switched their oral contraceptive (OC) to 2.0 mg chlormadinone acetate (CMA)/0.03 mg ethinylestradiol (EE) (Belara). MATERIALS AND METHODS: In a total of 20,897 women who were enrolled in a four-cycle clinical evaluation at 1597 gynecological practices throughout Germany, there are 16,781 women who switched from another contraceptive. RESULTS: The most frequently mentioned complaint for switching contraceptive was seborrhea/acne (6933/16,781 women; 41.3%). This was followed by cycle irregularities (18.8%), headache (15.9%), breast tension (15.1%), amenorrhea (14.9%), spotting (12.8%) and dysmenorrhea (11.7%). After switching to CMA/EE treatment, these symptoms decreased substantially or even disappeared in a large number of women. The vast majority of study participants scored both tolerability and well-being on CMA/EE intake as 'very good' or 'good'. The results revealed that 13,508 women (80.5%) stated being more satisfied or even much more satisfied on CMA/EE intake compared to their previously used contraceptive; most of them had taken progestins of the nortestosterone type. CMA/EE produced beneficial effects on skin conditions and well-being in OC switchers who experienced dissatisfaction with their previous contraceptive regimen. CONCLUSION: The results of this observational study support that 2.0 mg CMA/0.03 mg EE is well tolerated, provides a reliable cycle stability and is very effective in diminishing dysmenorrhea and other cycle-related complaints. Women suffering from problems on hormonal contraception received benefit from switching to the progesterone derivative CMA-containing OC.

Reproductive and transcriptional effects of the antiandrogenic progestin chlormadinone acetate in zebrafish (Danio rerio).

Chlormadinone acetate (CMA) is a frequently used progestin with antiandrogenic activity in humans. Residues may enter the aquatic environment but potential adverse effects in fish are unknown. While our previous work focused on effects of CMA in vitro and in zebrafish eleuthero-embryos, the present study reports on reproductive and transcriptional effects in adult female and male zebrafish (Danio rerio). We performed a reproductive study using breeding groups of zebrafish. After 15 days of pre-exposure, we exposed zebrafish to different measured concentrations between 6.4 and 53,745 ng/L CMA for 21 days and counted produced eggs daily to determine fecundity. Additionally, transcriptional effects of CMA in brains, livers, and gonads were analyzed. CMA induced a slight but statistically significant reduction in fecundity at 65 ng/L and 53,745 ng/L compared to pre-exposure. Furthermore, we observed differential expression for gene transcripts of steroid hormone receptors, genes related to the hypothalamic-pituitary-gonadal axis, and steroidogenesis. In particular, we found a significant decrease of transcript levels of vitellogenin (vtg1) in ovaries and liver, and of cyp2k7 in the liver of males, as well as a significant increase of transcripts of the progesterone receptor (pgr) in testes, and cyp2k1 in the liver of females. The observed effects were weaker than those of other very potent progestins, which is probably related to the lack of interaction of CMA with the zebrafish progesterone receptor.

A five-day gradual reduction regimen of chlormadinone reduces premenstrual anxiety and depression: a pilot study.

BACKGROUND: Anxiety and depression commonly occur in premenstrual dysphoric disorder (PMDD). The PMDD symptomatology disappears once the menstrual cycle reinitiates, resembling a withdrawal syndrome. METHODS: The present study is a pilot, controlled, double-blind study exploring the effectiveness of a premenstrual 5-day gradual reduction regimen of chlormadinone acetate on PMDD. Volunteers received an initial dose of 10 mg (five 2-mg tablets) on the 24(th) day of the menstrual cycle and one-fifth of the dose less (one tablet) each day until a dose of 2 mg (one 2-mg tablet) was reached on the 28(th) day of the menstrual cycle. The control group received placebo with a similar regimen. RESULTS: The 5-day gradual reduction regimen of chlormadinone significantly improved (F(3.76) = 3.29, p <0.02) the daily symptoms report (DSR) scores by the third month of treatment. The resulting relative risk was 4.09 (confidence interval: 1.15-14.57, p <0.005, 95% CI). Compared to placebo, chlormadinone clinically and statistically reduced the severity of depression, anxiety, food cravings, mood swings and cramps. A statistical reduction of symptoms such as poor coordination, irritability, feeling out of control, hopelessness, decreased interest and headache was detected but was not clinically relevant. No changes occurred in concentration difficulties, tiredness, insomnia, swelling, breast tenderness and aches. As side effects, 30% of the volunteers showed changes in the length of the menstrual cycle, and 15% experienced dyspepsia. CONCLUSIONS: A 5-day gradual reduction regimen of chlormadinone improves some of the discomforting ailments associated with PMDD, namely, depression and anxiety.

Impact of progestagens on activated protein C (APC) resistance among users of oral contraceptives.

Oral contraceptive (OC) use is associated with an increased risk of venous thromboembolism. Previous data reported higher thrombotic risk in women using third-generation combined OC than in those using second generation OC. The difference could be explained by differential effects of progestagens on plasma sensitivity to activated protein C (APC). The main purpose of this cross-sectional study was to assess the influence of a progestagen-only OC (chlormadinone acetate) as well as the effect of several combined OC with different progestagen components on APC resistance. The effect of APC on endogenous thrombin potential (ETP) was investigated in the plasma of healthy women using either combined OC (n=82) or progestagen-only OC (n=28), and in non-users (n=64). Carriers of factor V Leiden were excluded. Compared with non-users, there was no significant change in APC resistance in women using progestagen-only OC. Women who used combined OC were less sensitive to APC than non-users (P < 0.001) and the difference was significantly more pronounced in women using third-generation OC (n=41) than in those who used second-generation OC containing levonorgestrel (n=22) (P < 0.05). Compared with OC containing levonorgestrel, use of norethisterone-containing OC (n = 9) was associated with an increased resistance to APC (P < 0.05). Women who used cyproterone-containing OC (n = 10) were less sensitive to APC than those using third-generation OC (P < 0.05) or second-generation OC containing levonorgestrel (P < 0.05). Protein S, factor II and FVIII levels explained in part the OC-related changes in APC sensitivity variations. ETP-based APC resistance may contribute to explain why different brands of OC can be associated with different levels of thrombogenicity.

Progestogens with antiandrogenic properties.

Chlormadinone acetate, cyproterone acetate and dienogest are potent, orally active progestogens, which have antiandrogenic instead of partial androgenic activity. They act mainly by blocking androgen receptors in target organs, but also reduce the activity of skin 5alpha-reductase, the enzyme responsible for converting testosterone to the more potent androgen, 5alpha-dihydrotestosterone, in sebaceous glands and hair follicles. Chlormadinone acetate and cyproterone acetate also suppress gonadotropin secretion, thereby reducing ovarian and adrenal androgen production. Combined oral contraceptives (COCs) containing antiandrogenic progestogens provide highly effective contraception (gross and adjusted Pearl indices: 0-0.7 and 0-0.3, respectively) with excellent cycle control. Furthermore, COCs containing 2mg of chlormadinone acetate or cyproterone acetate plus 30 or 35 microg of ethinylestradiol produced improvement or resolution of seborrhoea in 80% of users, acne in 59-70%, hirsutism in 36% and androgen-related alopecia in up to 86%. These COCs are generally well tolerated, the main adverse effects being nonspecific or as expected for a COC (headache, breast tenderness and nausea). They have no clinically relevant effects on metabolic or liver functions or on bodyweight. Effects on mood and libido are uncommon (<3.5% and <6% of women, respectively). COCs containing antiandrogenic progestogens are likely to be particularly valuable in women with pre-existing androgen-related disorders who require contraception. They also increase the choice of products available for women with normal skin and hair who are concerned about the possibility of developing seborrhoea or acne with other COCs.

Insulin and glucose studies after one year of treatment with a sequential-type oral contraceptive.

PIP: Plasma insulin and blood glucose were measured during an intravenous glucose tolerance test at the University of Minnesota hospital clinic on 28 women on oral sequential contraceptives (15 tablets of 80 mu-g mestranol, 5 tablets of 80 MCG mestranol and 2 mg chlormadinone acetate) both prior to drug initiation and after 1 year of use. No statistical difference in either glucose or insulin levels or weight change was seen after 1 year of therapy. A significant positive association was found between the elevation of glucose and insulin with the drug at cerain time periods during the glucose test, and if there was a family history of diabetes mellitus. A higher frequency of abnormal glucose and insulin levels has been found among users of combination-type drugs as compared to the sequential type.^ieng

Antiandrogen withdrawal syndrome in prostate cancer after treatment with steroidal antiandrogen chlormadinone acetate.

OBJECTIVES: A case report is presented of 2 patients whose levels of serum prostate-specific antigen (PSA) improved after the withdrawal of a steroidal antiandrogen. METHODS: Two cases with prostate cancer had been treated with surgical castration and the steroidal antiandrogen chlormadinone acetate (CMA), and, on disease progression, the administration of CMA was terminated. RESULTS: Following withdrawal of CMA, a fall in PSA levels and remarkable clinical improvement were observed in both cases. One patient revealed a decrease and the other an increase in serum prostate acid phosphatase after the discontinuation of CMA. Serum levels of testosterone, prolactin, dehydroepiandrosterone, dehydroepiandrosterone sulfate, and androstenedione were not significantly elevated after CMA withdrawal. CONCLUSIONS: Withdrawal of the steroidal antiandrogen CMA resulted in a decline in PSA levels and clinical improvement in prostate cancer patients with disease progression. Changes in testosterone, prolactin, or adrenal androgens were not a cause of the antiandrogen withdrawal syndrome.

Mesenteric venous thrombosis in two women taking oral contraceptives.

PIP: 2 cases of mesenteric venous thrombosis in women taking oral contraceptives (48-year old gravida 5 taking norethindrone with mestranol for 10 years, a 33-year old gravida 2 taking Enovid and C-Quens since 1962 followed by norethindrone with mestranol 1 month prior to admission) were treated at the Jewish Hospital of St. Louis. Both patients had acute abdominal pain, vomiting, and bloody and diarrheal stools. In order to remove nonviable portions of the bowel which are viable at initail operation, 2 operations are necessary in the treatment of mesenteric venous thrombosis. Both of these patients underwent 2 operations and both had extensive segments of bowel removed. The post-operative courses of both patients were long (85 and 40 days respectively) and difficult. No predisposing or etiologic factor could be determined in either patient. A relationship of mesenteric venous thrombosis to oral contraceptives is suggested, but no definite causal relationship can be established.^ieng

Continuous hormone replacement therapy with estradiol valerate and chlormadinone acetate in adjustable dosages. A preliminary study.

A group of 62 peri- and postmenopausal women suffering from vasomotor disturbances and a variety of other symptoms were treated with estradiol valerate and chlormadinone acetate continuously using an adjustable dosage regimen. They obtained complete relief from vasomotor symptoms. The continuation rate was 81% after 1 year. In 18 patients the dose had to be adjusted because of breakthrough bleeding (n = 12), mastodynia (n = 3), and for the prevention of bone loss. In 11/12 patients breakthrough bleeding could be stopped by adjusting the dosage. This regimen seems to offer a more flexible approach to hormone replacement therapy (HRT) in the postmenopause than presently available combined preparations for continuous use.