The effects of 2 mg chlormadinone acetate/30 mcg ethinylestradiol, alone or combined with spironolactone, on cardiovascular risk markers in women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is an endocrine disorder associated with metabolic dysfunction and changes in cardiovascular risk markers, and using oral contraceptives (OCs) may exert a further negative effect on these alterations in patients with PCOS. Thus, the primary objective of this study was to assess the effects on arterial function and structure of an OC containing chlormadinone acetate (2 mg) and ethinylestradiol (30 mcg), alone or combined with spironolactone (OC+SPL), in patients with PCOS. STUDY DESIGN: This was a randomized, controlled clinical trial. Fifty women with PCOS between 18 and 35 years of age were randomized by a computer program to use OC or OC+SPL. Brachial artery flow-mediated vasodilation, carotid intima-media thickness and the carotid artery stiffness index were evaluated at baseline and after 6 and 12 months. Serum markers for cardiovascular disease were also analyzed. The intragroup data were analyzed using analysis of variance with Tukey's post hoc test. A multivariate linear regression model was used to analyze the intergroup data. RESULTS: At 12 months, the increase in mean total cholesterol levels was greater in the OC+SPL group than in the OC group (27% vs. 13%, respectively; p=.02). The increase in mean sex hormone-binding globulin levels was greater in the OC group than in the OC+SPL group (424% vs. 364%, respectively; p=.01). No statistically significant differences between the groups were found for any of the other variables. CONCLUSION: The addition of spironolactone to an OC containing chlormadinone acetate and ethinylestradiol conferred no cardiovascular risk-marker advantages in young women with PCOS.

Oral contraceptive containing chlormadinone acetate and ethinylestradiol reduces plasma concentrations of matrix metalloproteinase-2 in women with polycystic ovary syndrome.

Biochemical markers of cardiovascular disease, including matrix metalloproteinases (MMPs), are altered in women with polycystic ovary syndrome (PCOS), with many of these alterations thought to be due to excess androgen concentrations. Despite oral contraceptives (OCs) being the first-line pharmacological treatment in women with PCOS and the importance of MMPs in many physiological conditions and pathological states, including cardiovascular diseases, no study has yet evaluated whether OCs alter plasma concentrations of MMPs. We therefore assessed whether treatment with an OC containing the anti-androgenic progestogen alters MMP profiles in women with PCOS. We analysed 20 women with PCOS who wanted hormonal contraception (OC-PCOS group), 20 ovulatory women who required hormonal contraception (OC-control group) and 20 ovulatory women who wanted non-hormonal contraception (non-OC-control group). OC consisted of cyclic use of 2 mg chlormadinone acetate/30 µg ethinylestradiol for 6 months. Plasma concentrations of MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured by gelatin zymography or enzyme-linked immunoassays. OC treatment for 6 months significantly reduced plasma MMP-2 concentrations in the OC-control and OC-PCOS groups and TIMP-2 and TIMP-1 concentrations levels in the OC-control group (all p < 0.05), but had no effects on MMP-9 concentrations or on MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios in any group (all p > 0.05). These findings indicated that long-term treatment with an OC containing chlormadinone acetate plus ethinylestradiol reduced plasma MMP-2 concentrations in both healthy and PCOS women. As the latter have imbalances in circulating matrix MMPs, treatment of these women with an OC may be beneficial.

Progestin treatment for infertility in bitches with short interestrus interval.

The purpose of this study was to investigate if the suppression of estrus by the administration of a synthetic progestin, megestrol acetate or clormadinone acetate, could be an effective treatment to infertility in bitches with shortened interestrus periods and previous infertility. Ten bitches of different breeds and ages, with history of infertility and presenting repeated interestrus intervals of less than 4 months, were treated daily either with megestrol acetate (2 mg/kg, n = 8) or clormadinone acetate (0.5 mg/kg, n = 2) orally for 8 days. The treatments were begun within a maximum of 3 days after the onset of clinical signs of proestrus. Estrus was prevented in all animals and appearance of the following proestrus cycle was observed within 2.7 +/- 0.6 months (mean +/- S.D.) after the beginning of the treatment. When mated during the first post-treatment estrous cycle, bitches became pregnant and whelped normal healthy offspring. No negative side effects were clinically detected over the study period. Our results show that, in bitches with shortened interestrus intervals and previous infertility, suppression of one estrus with synthetic progestins administered at recommended doses, allows fertile breedings on the subsequent cycle, producing litter sizes within the normal range.

[Ocular changes after hormone replacement therapy in postmenopausal women. A preliminary report]. / Cambios oculares posteriores a la administración de tratamiento hormonal en mujeres posmenopáusicas. Reporte preliminar.

BACKGROUND: Ocular function is modified with hormone therapy; however, reports in literature are highly controversial. OBJECTIVE: To analyze how hormone therapy modifies intraocular pressure and the number of tears shed by Mexican women. PATIENTS AND METHODS: Eighteen postmenopausal women were studied and randomly divided into two groups, according to the treatment they received: group 1, conjugated equine estrogens (CEE) 0.625 mg/day (n=9) (hysterectomized women with bilateral oophorectomy) and group 2, CEE 0.625 mg/day plus chlormadinone 1 mg/day (n=9) (women with intact uterus). Changes in intraocular pressure and Schirmer's test were analyzed at baseline and three months after the treatment. Statistical analysis was performed with Student's t test for independent and paired samples. RESULTS: There were no significant differences in intraocular pressure or Schirmer's test among groups, neither when comparing baseline and final results in each group independently. CONCLUSION: We could not demonstrate the effect of hormone replacement therapy on intraocular pressure and on Schirmer's test after three months of its administration.

[Ultrasonographic and lipid changes in polycystic ovary syndrome according to the type of treatment ]. / Cambios ultrasonográficos y en lípidos en el síndrome de ovario poliquístico de acuerdo al tipo de tratamiento.

OBJECTIVE: To determine the ultrasonographic and lipid changes in women with polycystic ovary syndrome (PCOS) according to the type of hormonal treatment. STUDY DESIGN: Thirty-two women with clinical and ultrasonographic diagnosis of PCOS were studied and randomly distributed in one or another treatment group. Group I: chlormadinone (2 mg/day for 5 days every month) (n = 16) and Group II: ethinylestradiol 35 micrograms plus desogestrel 150 mg (21 days every month) (n = 16). At baseline and at third month a pelvic ultrasound was done to assess the number and size of follicles, also total cholesterol and triglycerides were measured. RESULTS: In both groups a significant decrease was found in the number of follicles in both ovaries, but only in group II there was a significant decrease in follicular size in both ovaries. No differences were found between the groups in the number of follicles or in the final follicular size. In both groups, a significant decrease was found in total cholesterol levels, without changes in triglycerides levels. CONCLUSION: Only combined therapy decreased follicular size. So the type of treatment should be based on patient expectations such as sexual activity, or for control of androgen excess.

[Premature ovarian failure and pregnancy]. / Falla ovárica prematura y embarazo.

Two cases of premature ovarian failure (POF) diagnosed by clinical symptomatology, persistently elevated levels of gonadotropins and hypoestrogenism, are presented. Gonadal biopsy was done on the patients, which disclosed no evidence of primordial follicles in one and severe reduction in the other. Estrogen substitutive therapy was started to ameliorate their menopausal symptoms and spontaneously conceived. A review of the literature related to the syndrome is presented.

[Dysfunctional uterine bleeding. Hormonal management with chlormadinone acetate]. / Sangrado uterino disfunctional. Manejo hormonal con acetato de clormadinona.

In 138 patients with uterine dysfunctional bleeding a hormonal treatment with chlormadinone acetate, was given. The dosage varied according to four therapeutic stages: hemostatic, maintenance, consolidation and observation. Patients were placed in three groups: Group I, adolescents, Group II, reproductive life, Group III, premenopausal. In 51.9% of the patients there was endometrial hyperplasia, proliferative in 26.6% and secretory in 14.1%. Good results were obtained in all four therapeutic stages.

[Effect of chlormandinone acetate upon seizures in epileptic children with latent signs of hyperandrogenism]. / Efecto del acetato de clormadinona sobre las crisis convulsivas en niños epilèpticos con signos sugestivos de hiperandrogenismo

The effect of chlormadinone acetate (24 mg/day) upon the plasma levels of pituitary gonadotropins and gonadal hormones on the number of generalized convulsions and spike EEG density was investigated in a group of epileptic children with intractable seizures and with clinical signs suggestive of hyperandrogenism. In each case, the effect of chlormadinone was evaluated in relation to hormonal levels and seizures observed during a control period and under the effect of placebo as follows: Control (PC)-Chlormadinone acetate (PCL1)-Placebo (PP)-Chlormadinone acetate (PCL2). In a male child (4MS), the number of convulsive attacks observed in the control period (26/month) was reduced during PCL1 (2/month) increased during PP (12/month) and was reduced again during PCL2 (0/month). Spike EEG density showed a parallel course to the clinical attacks. In this case, control levels of testosterone were markedly elevated (40 ng/ml) and were decreased during PCL1 to 4.0 increased again during PP to 34.0 and decreased again during PCL2 to 1.2 ng/ml. Plasma levels of pituitary gonadotropins were unchanged throughout the entire period of study. In other cases, neither the number of epileptic attacks nor spike EEG density were apparently affected by this regime and plasma levels of pituitary gonadotropins and gonadal hormones were also unmodified. These results suggest that a latent state of hyperandrogenism may be detected in some epileptic patients with intractable seizures and that chlormadinone may reduce convulsive attacks in these patients, probably by decreasing testosterone plasma levels.

PIP: The effect of chlormadinone acetate (24 mg/day) upon the plasma levels of pituitary gonadotropins and gonadal hormones on the number of generalized convulsions and spike EEG density was studied in a group of epileptic children with intractable seizures and with clinical signs suggestive of hyperandrogenism. In each case, the effect of chlormadino ne was evaluated in relation to hormone levels and seizures observed during a control period and under the effect of placebo, as follows: Control (PC); Chlormadinone acetate (PCL1); Placebo (PP); Chlormadinone acetate (PCL2). In a male child, the number of convulsive attacks observed in the control period (26/month) was reduced during PCL1 (2/month), increased during PP (12/month) and reduced again during PCL2 (0/month). Spike EEG density showed a parallel course to the clinical attacks. In this case, control testosterone levels were markedly high (40 ng/ml) and decreased during PCL1 to 4.0, increased again during PP to 34.0 and decreased again during PCL2 to 1.2 ng/ml. Plasma levels of pituitary gonadotropins were unchanged during the entire period of study. In other cases, neither the number of epileptic attacks nor spik e EEG density were apparently affected by this treatment and plasma levels of pituitary gonadotropins and gonadal hormones were also unchanged. These findings suggest that a latent state of hyperandrogenism may be detected in some epileptic patients with intractable seizures and that chlormadinone may reduce convulsive attacks in these patients, probably by decreasing plasma testosterone levels.