Administration Of Chlormadinone Acetate Research Articles

Clinical utility of chlormadinone acetate (Lutoral™) in frozen-thawed embryo transfer with hormone replacement.

PurposeThe clinical utility of chlormadinone acetate tablets (Lutoral™), an orally active progestin which has been available since June 2007, was compared to an in‐house vaginal suppository formulation of progesterone used between 2006 and 2007 for assisted reproductive technology (ART).MethodsWe retrospectively evaluated the efficacy and safety of chlormadinone acetate by comparing the pregnancy rates and the incidences of birth defects and hypospadias in frozen‐thawed embryo transfer cycles using the in‐house vaginal progesterone and those using chlormadinone acetate for luteal phase support.ResultsThe pregnancy rates in the frozen‐thawed embryo transfer cycles were 31.2% (259/831) with vaginal progesterone for luteal phase support and 31.6% (4228/13 381) with chlormadinone acetate (no significant difference). In the cycles resulting in live birth following administration of chlormadinone acetate between July 2007 and December 2015, the incidence of birth defects was 2.8% (80/2893), and the incidence of hypospadias was 0.03% (1/2893).ConclusionsThese results indicate that the pregnancy rate following frozen‐thawed embryo transfer using chlormadinone acetate for luteal phase support was comparable with that using vaginal progesterone, with no increased risk of birth defects, including hypospadias, which has been a concern following the use of progestins.

Abstract 956: Targeting prostate cancer chemoprevention via the androgen receptor in a preclinical mouse model

Abstract Prostate cancer is strongly associated with increasing age, with about 96 % of the cases occurring in men over 60 years of age. The high incidence and late age of onset make prostate cancer an ideal target for chemoprevention strategies as even a modest delay in carcinogenesis would significantly reduce the incidence of the disease. Chlormadinone acetate (CA) is one of the steroidal anti-androgen agents used in combined androgen blockade therapy as well as monotherapy for prostate cancer in Japan. However, no reports have been published for the chemopreventive potential of CA. We evaluated the efficacy of low-dose administration of CA to prevent or suppress prostate cancer using our PTEN conditional gene targeting mouse model. Six-week-old mice were injected subcutaneously with CA (50 mg/kg 3X/week) until the age of 15 or 20 weeks. The genitourinary tracts (GUTs), consisting of the prostate, urethra, bladder, seminal vesicles and coagulating gland, were collected, weighed, fixed in formalin and imaged. GUT weights were significantly lower in CA-treated mice compared to untreated controls in a time dependent manner (P<0.01). Morphometric image analysis performed on the GUT to measure the prostate area revealed significant shrinkage of the prostate gland in CA-treated mice vs. the corresponding controls (P<0.001). Histopathological distribution analysis of normal, prostatic intraepithelial neoplasia (PIN) and tumor glands showed a decrease in the PIN but not normal or cancer glands in 15-week-old CA-treated mice compared to controls. However, similar analysis showed a dramatic decrease of cancer gland shrinkage in 20-week-old CA-treated mice with only marginal decreases of PIN compared to untreated controls. Immunohistochemical analysis of androgen receptor (AR) expression showed a significant decrease in nuclear localization and intensity CA-treated mice (P<0.001). Proliferation analysis of tumors by PCNA immunostaining showed a 30% reduction in 20-week-old mice treated with CA compared to untreated control mice (P<0.001). The apoptotic index in tumors if mice treated with CA increased three-fold to 3.16% compared to 1.12% on the corresponding control mice (P<0.004). Our data suggests that chemopreventive treatment with CA does not prevent the incidence of prostate cancer, however, it does inhibit the growth and progression of prostate cancer. Our findings may reveal a promising prophylactic strategy for the chemopreventive treatment of prostate cancer in high-risk individuals. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 956.

Suppression of ovarian function by a combined oral contraceptive containing 0.02 mg ethinyl estradiol and 2 mg chlormadinone acetate given in a 24/4-day intake regimen over three cycles

To describe the suppression of ovarian function with 0.02 mg ethinyl E(2)-2 mg chlormadinone acetate administered in a 24/4-day intake regimen in healthy women. Open, uncontrolled, multiple dosing, phase II trial. Single clinic. Forty women treated. Treatment for up to three cycles with 0.02 mg ethinyl E(2)-2 mg chlormadinone acetate given in a 24/4-day regimen. Assessments of ovarian function classified by the Hoogland and Skouby score, thickness of endometrium, cervical reaction, and sex hormone levels, as well as overall tolerability. No ovulation was observed in the per protocol set (N=36), and one in the full analysis set (N=38) after vomiting and diarrhea. Absence of ovarian activity, residual ovarian activity, and formation of a luteinized unruptured follicle were observed in 75.0%, 15.9%, and 1.1% of medication cycles, respectively. Endometrial thickness was suppressed to 4 to 5 mm compared with 10 to 12 mm without medication. Cervical reaction was negative. Hormone levels were lower with medication than without, and the medication was well tolerated. Treatment-related adverse events were typical of those associated with hormonal contraceptive use. Follicular development, cervical reaction, and endometrial thickness were suppressed profoundly after 0.02 mg ethinyl E(2)-2 mg chlormadinone acetate administration in a 24/4-day regimen, resulting in inhibition of ovulation and unfavorable conditions for fertilization, implantation, and thus pregnancy.

Selective effect of chlormadinone acetate on brain allopregnanolone and opioids content

Background Synthetic progestins may have different biological actions depending on the target tissue, the dose administered or the coadministration of an estrogen molecule. The purpose of the present study was to evaluate the neuroendocrine effect of chlormadinone acetate (CMA) administration, analyzing the brain content of allopregnanolone (ALLO), an endogenous neurosteroid γ-aminobutyric acid agonist with anxiolytic properties, and the brain level of β-endorphin (β-END), an endogenous opioid implicated in pain mechanism, emotional state and autonomic control. Study Design Seven groups of Wistar ovariectomized (OVX) rats received one of the following treatments: oral CMA at a dose of 0.1, 0.5 or 1 mg/kg per day; estradiol valerate (E 2V) at a dose of 0.05 mg/kg per day; CMA plus E 2V (CMA 0.1 or 0.5 or 1 mg/kg per day + E 2V 0.05 mg/kg per day) for 14 days. One group of fertile rats and one group of OVX rats were used as controls. Results CMA increased ALLO content in the hippocampus and, when it was administered with E 2V, also in the hypothalamus and anterior pituitary, evidence of a synergic effect with estrogens only in selective brain areas. β-END content increased in the neurointermediate lobe and anterior pituitary after CMA administration, and it did not antagonize the positive, estrogen-induced increase of β-END level. Conclusion CMA is effective in increasing ALLO and β-END in selective brain areas showing a specific pattern of interaction with brain function, different compared to progesterone or to other synthetic progestins. In particular, CMA action on part of the limbic system (hippocampus and hypothalamus) and on the anterior pituitary support the hypothesis that this progestin might affect cognitive function, emotional state and autonomic control.

Prostate‐specific antigen changes as a result of chlormadinone acetate administration to patients with benign prostatic hyperplasia: A retrospective multi‐institutional study

Antiandrogens used to treat benign prostatic hyperplasia (BPH) may affect the diagnosis of prostate cancer by decreasing serum prostate-specific antigen (PSA) values. We conducted a retrospective survey of BPH patients treated with chlormadinone acetate (CMA) and analysed the effect of CMA on their PSA values. A chart-based, retrospective, multi-institutional survey of clinically diagnosed patients with BPH who had been treated with CMA (Prostal; 50 mg/day) was conducted. The patients were divided into three groups according to their baseline PSA values: <4 ng/mL, Group I; >or=4 ng/mL and <10 ng/mL, Group II; and >or=10 ng/mL, Group III. The changes in the PSA values from baseline after 16, 26, and 52 weeks of CMA therapy were predicted using a nonlinear regression model analysis. Data from 192 of the 303 enrolled patients were analysed. The predicted percent changes from baseline among all patients after 16, 26, and 52 weeks of treatment were -49.6%, -49.8%, and -49.9%, respectively. The corresponding values were -42.4%, -43.7% and -43.8% in Group I; -57.4%, -58.4% and -58.5% in Group II; and -50.6%, -50.6% and -50.6% in Group III, respectively. The PSA values reached a nadir, approximately -50% of the baseline, after 16 weeks of CMA administration and remained at the same level thereafter. When CMA is used to treat BPH patients, the possibility of abnormal increases in PSA associated with prostate cancer must be considered; if prostate cancer is suspected, prompt testing, including a biopsy, should be performed.

Preoperative administration of chlormadinone acetate reduces blood loss associated with transurethral resection of the prostate: a prospective randomized study

To assess the effects of giving chlormadinone acetate (CMA) before surgery on blood loss associated with transurethral resection of the prostate (TURP), in a prospective randomized controlled study. Candidates for TURP among patients with benign prostatic hyperplasia were randomized to either treatment with CMA (CMA+) or not (CMA-). In principle, CMA was started at least 28 days before TURP and continued until just before surgery. In all, 33 patients in the CMA+ (median duration of treatment 34.5 days) and 38 in the CMA- group were evaluable. The mean blood loss during TURP was less in the CMA+ (237.3 mL) than in the CMA- group (263.1 mL), but the difference was not significant. There was significantly less blood loss per gram of resected prostate tissue in the CMA+ (9.6 mL/g) than in the CMA- group (13.3 mL/g) (P < 0.05). Haematuria on the day of and the day after TURP was also significantly less severe in the CMA+ than in the CMA- group (P < 0.001 and P < 0.05, respectively). The mean microvessel density of resected prostate tissue was significantly less after CMA treatment (P < 0.001). CMA given for 1 month before TURP could reduce blood loss to some extent during and after TURP, and this may be related to a decrease in microvessel density.

Hormonal and morphologic evaluation of the effects of antiandrogens on the blood supply of the rat prostate

Objectives To clarify the basic aspects of the regulation of the prostatic blood supply by antiandrogens, their effect on the prostatic blood supply was studied for both androgen content and morphology of true capillaries in the rat ventral prostate. The effectiveness of antiandrogens on the control of hemorrhagic status in prostatic diseases has been previously reported. Methods Androgen concentrations in the prostate were quantified after administration of chlormadinone acetate (CMA), finasteride, or flutamide. The prostatic blood supplies were measured after administration of CMA, finasteride, flutamide, or bicalutamide. The alpha-blockers, terazosin and tamsulosin, were included in the study as negative controls. The histologic changes in the capillaries of the ventral prostate were observed, and the luminal area was measured. Results The prostate dihydrotestosterone concentrations were decreased by the administration of all antiandrogens. Treatment with CMA, finasteride, flutamide, or bicalutamide reduced the prostatic blood supply by 50% to 65%. The parallel reduction in luminal areas of the true capillaries was observed in rats treated with CMA. Treatment with alpha-blockers did not affect the prostate androgen content, prostatic blood supply, or capillary luminal area. Conclusions The reduction of the prostatic blood supply was suggested to be the result of a decrease in dihydrotestosterone content and the reduction in the luminal area of capillaries. The early reductive effect of antiandrogens on the prostatic blood supply suggests an alternative use for antiandrogens independent of their typical use for prostate volume regression. The results support the basic aspects of the advantage of preoperative treatment with CMA, flutamide, and bicalutamide, similar to finasteride, in reducing perioperative hemorrhage.

Low-dose conjugated equine estrogens elevate circulating neurotransmitters and improve the psychological well-being of menopausal women

Objective: To assess the effect of low-dose conjugated equine estrogens (E) on circulating neurotransmitters and the efficacy for the treatment of psychological symptoms. Design: Controlled comparative clinical study. Setting: Endocrine Research Unit, Instituto Mexicano del Seguro Social, Mexico. Patient(s): Thirty postmenopausal women received conjugated equine E. Ten women acted as a comparison group. Intervention(s): Conjugated equine E, 0.312 mg/day, for 21 days per cycle during six cycles and added chlormadinone acetate, 2 mg/day, for the last 5 days of each cycle. Green scale for climateric women and Blatt-Kupperman Menopausal Index were used for measuring psychological well-being. Main Outcome Measure(s): Serum levels of dopamine (DA), noradrenaline, serotonin, and β-endorphin were quantified by specific assays at baseline and at the end of treatment. Result(s): Low baseline levels of DA, serotonin, and β-endorphin increased significantly ( P<.001) from 181.9 ± 47.8 pg/mL to 202.9 ± 32.8 pg/mL (mean ± SD); from 206.4 ± 94.2 ng/mL to 279.2 ± 67.9 ng/mL; from 11.2 ± 1.8 pmol/L to 13.8 ± 2.4 pmol/L, respectively, after conjugated equine E. In parallel, augmented baseline noradrenaline levels diminished significantly ( P<.05) from 30.2 ± 4.7 ng/mL to 24.0 ± 4.7 ng/mL. All neurotransmitter levels had a significant correlation with 17β-E 2 concentrations at the end of the study. Alleviation of psychological symptoms was observed in all but eight treated women. Conclusion(s): Low-dose conjugated equine E associated with periodic administration of chlormadinone acetate elicited favorable changes in neurotransmitters and relieved psychological symptoms.

進行期の乳房外パジェット癌に対する抗アンドロゲン療法の試み

Growth dependence with androgen (Nishi J Natl Cancer Inst 84: 519, 1992) and frequent expression of structurally unaltered androgen receptor (Fujimoto Lab Invest 80: 1465, 2000) in Extramammary Paget's disease (EMPD) may provide arational basis for hormone therapy. We report the first attempt of total androgen blockade (TAB) therapy in a 78-year-old man with advanced EMPD. The TAB therapy, which is widely used for prostate cancer, consisted. of oral administration of chlormadinone acetate 100mg daily and subcutaneous injection of leuprorelin acetate 3.75mg every month. Although skin metastases on his lower abdomen gradually progressed, para-trachial lymphadenopathy disappeared and para-aortic lymph nodes decreased in size by more than 60%. He died of the disease one year after starting the TAB therapy. Future clinical trial is required to establish the role of TAB therapy in the management of advanced stage EMPD patients. [Skin Cancer (Japan) 2001; 16: 247-250]

A clinical study of secondary osteoporosis induced by endocrine therapy for prostate cancer

There is one of the big problems that endocrine therapy for prostate cancer causes to induce secondary osteoporosis. The risk factors and future treatments for osteoporosis were investigated. 31 patients treated with luteinizing hormone releasing hormone agonists (LHRH-a) or combination of chlormadinone acetate (CMA) and LHRH-a, and 19 patients with no treatments for prostate cancer were included in the analysis. Lumber spine bone mineral density (BMD) was measured by quantitative computed tomography. Aging had much influence on decreases of BMD than the other risk factors (p < 0.01). There were statistically decreases of BMD in the patients with CMA + LHRH-a compared with no treatments (p < 0.05). Adrenal androgen which had an important role of maintenance in BMD was statistically decreased by the administration of CMA (p < 0.01). Measurement of BMD before endocrine therapy is necessary for the patients with prostate cancer. It is important for the patients with decreases of BMD that CMA is not combined or the therapy for osteoporosis is preventively employed.

Incidence and Characteristics of Antiandrogen Withdrawal Syndrome in Prostate Cancer after Treatment with Chlormadinone Acetate

Objectives: In patients with progressive prostate cancer who have been treated with surgical or medical castration plus an antiandrogen, antiandrogen withdrawal can result in a significant decline in serum prostate-specific antigen (PSA). Although the incidence of antiandrogen withdrawal syndrome after combination treatment with the nonsteroidal antiandrogen flutamide has been thoroughly documented, the phenomenon clearly occurs in many other combination therapies and is presently being widely investigated. This paper would like to contribute to this effort by describing the endocrine withdrawal phenomenon in patients treated with combinations of castration plus chlormadinone acetate, ethynylestradiol or estramustine phosphate. Materials and Methods: Clinical records of 68 prostate cancer patients who had been treated with surgical castration plus the administration of chlormadinone acetate, ethynylestradiol or estramustine phosphate, and who had shown clinical progression associated with a steady increase in serum PSA, were investigated. Forty-one cases were evaluable for changes in PSA after discontinuation of the hormonal agents. Results: Of 28 patients who had been treated with chlormadinone acetate, 12 (42.9%) revealed 50% or more decline in PSA level following withdrawal of the agent. Among these, 5 cases (17.9%) showed subjective and/or objective improvements. There was no significant difference in histological grade of the tumor at diagnosis, mode of progression, time interval from the start of endocrine therapy to discontinuation of the hormonal agents, or PSA levels at withdrawal of the agents between patients who did develop antiandrogen withdrawal syndrome and those who did not. Conclusion: When a steady increase in serum PSA is noted in a prostate cancer patient who has been treated with castration plus a steroidal antiandrogen, discontinuation of the antiandrogen may benefit the patient.

Chlormadinone acetate pellet implantation plus short-term oral administration in dogs with benign prostatic hypertrophy.

Eight beagles with benign prostatic hypertrophy (BPH) were treated by subcutaneous implantation of pellets containing 10 mg/kg chlormadinone acetate (CMA), a synthetic anti-androgen, plus daily oral administration of CMA at 2 mg/kg per day for 7 days as a therapy for BPH. Prostatic and testicular size were measured and prostatic and testicular biopsies were performed by laparotomy before and after CMA treatment. Plasma levels of luteininzing hormone (LH), testosterone and oestradiol were also measured. The clinical signs of BPH, for example haematuria and dysuria, resolved within 1 week of treatment. Mean prostatic volume decreased to 56% of the pretreatment value. At 40 weeks after treatment, prostatic volume had decreased by 36%. Histological examination of the prostate 1 week after treatment revealed reduction in diameter of the alveoli and in height of the glandular epithelium. Degeneration and atrophy of the glands were marked 4-12 weeks after treatment. In the testis, the diameter of seminiferous tubules and the number of germ cells in the seminiferous tubules had decreased markedly at 12 and 24 weeks after treatment. Although plasma LH concentrations did not undergo any marked fluctuations after CMA treatment, levels of testosterone and oestradiol were lower than before treatment. The results indicate that implantation of 10 mg/kg CMA, plus 7-day oral administration of 2 mg/kg CMA, bring about resolution of the clinical signs and marked reduction in prostatic volume within 1 week of treatment.

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.

Short-term oral treatment of canine benign prostatic hypertrophy with chlormadinone acetate.

Ten beagle dogs (4-8 years of age) with benign prostatic hypertrophy were treated daily for 7 or 14 days by a daily oral administration of chlormadinone acetate (CMA), an anti-androgenic preparation, at a dose of 0.5 or 2.0 mg/kg/day. The groups of dogs treated with CMA at a dose of 2.0 mg/kg showed a greater reduction of the prostatic volume during 7 or 14 days of treatment than the group treated with 0.5 mg/kg of CMA. At 56 and 84 days after the start of CMA treatment, prostate volume was reduced to 63 and 79% of the pre-administration volume, respectively. No marked decrease in plasma LH or testosterone was found after the CMA treatment. These results indicate that the therapeutic effects of 7-day oral treatment with CMA at 2.0 mg/kg/day in dogs with BPH last for about three months or longer without side effects.

Histological evaluation of benign prostatic hyperplasia treated by long-term administration of chlormadinone acetate (CMA).

Although the clinical effects of attempted nonsurgical treatment of benign prostatic hyperplasia have been well documented, detailed histological evaluation of the effects of treatment appears to be limited. The effect of long-term administration of an antiandrogen, chlormadinone acetate (CMA), on benign prostatic hyperplasia was evaluated with histological comparison of two biopsy specimens, one before treatment and one after treatment. Secretory epithelium showed obvious regressive changes with occasional basal cell prominence after CMA treatment. Stromal elements, however, did not show any marked changes, except for occasional edematous loosening. Scores of multiple epithelial parameters tended to be correlated with clinical improvement in urinary obstructive symptoms, especially in patients with predominant glandular hyperplasia. These results suggest that long-term administration of the potent antiandrogen CMA to inhibit dihydrotestosterone-receptor binding might be a useful therapeutic maneuver in patients with glandular hyperplasia, without any deterioration of the stromal component.

Effects of chlormadinone acetate, acetazolamide and oxygen on awake and asleep gas exchange in patients with chronic obstructive pulmonary disease (COPD)

The purpose of this study was to assess the short-term effects of chlormadinone acetate (CMA), a synthetic progestogen, acetazolamide (ACET) and oxygen on awake and asleep blood gas values. The study was conducted according to a randomized, double-blind and placebo-controlled design in 53 hypoxaemic patients with chronic obstructive pulmonary disease. On the first two consecutive nights, all patients received either room air or oxygen, via a nasal cannula, in random order. They then received either CMA (25 mg), ACET (250 mg) or placebo twice a day, all in identical capsules. On the third study night, after one week of drug treatment, the patients were tested breathing room air. CMA and ACET therapy decreased mean daytime arterial carbon dioxide tension (PaCO2) by 0.7 and 0.5 kPa, respectively, and night-time end-tidal carbon dioxide tension (PETCO2) by 0.5 and 0.3 kPa, respectively. Supplemental oxygen caused increased CO2 retention during the day and night (0.6 and 0.3 kPa, respectively. Daytime arterial oxygen tension (PaO2) increased to the same extent during ACET (1.9 kPa) and oxygen (2.5 kPa). Asleep oxygen saturation improved most with oxygen supplementation (7%), although ACET also caused significant improvement (4%). CMA administration had virtually no effect on mean awake and asleep hypoxaemia. ACET therapy significantly improved subjective sleep quality. On CMA, minute ventilation increased in association with an augmentation of the hypercapnic ventilatory response. ACET treatment increased both hypercapnic and hypoxic ventilatory responses. We conclude from the group of patients with COPD studied, that the short-term effects of ACET treatment on gas exchange compare favourably with those of CMA. Oxygen therapy improves oxygenation slightly more than ACET, but aggravates CO2 retention.

Prevention of estrus in the queen with chlormadinone acetate administered orally.

The possibility of estrus prevention in the queen by the oral administration of chlormadinone acetate was examined. The animals used were 29 mature and 15 immature queens. For 16 mature females, 4-12.5 mg was given daily by mouth for 7 days every 3 months. Ten of the 16 queens given this treatment came into estrus within 4 months of the first treatment. For 28 females including the immature, 2-12.5 mg was given once a week throughout the experiment. This treatment prevented estrous activity for at least 1 year. In the queens in this study, the side effects were not observed excepting an increase in body weight during treatment. Our results showed that oral administration of this drug weekly is safe and reliable for long-range prevention of estrus in queens.

Respiration Effect of Synthetic Progestin in Small Doses in Normal Men

Twelve healthy men were studied to determine the effect of ventilatory stimulation with chlormadinone acetate (CMA), a potent synthetic progesterone, in small doses (5 mg/day), on arterial blood gas levels. Using a randomized, double-blind, crossover trial, one week of CMA administration caused a significant reduction in arterial CO2 tension (PaCO2) by 4.1 +/- 2.9 (SD) mm Hg. The magnitude of the fall in PaCO2 was about the same as that obtained with dose of 50 mg per day in our previous study. The results indicate that the dosages of progestin and the effect of the drug on ventilation were not in parallel, and it may provide the idea that larger doses of progestin would not necessarily be required to stimulate ventilation.

Obese patients with sleep apnea syndrome treated by progesterone.

Two obese patients with sleep apnea syndrome were administered chlormadinone acetate (CMA), a synthetic progesterone, known as a potent respiratory stimulant to augment load compensation response as well as CO2 chemosensitivity. Before CMA administration, both cases showed normal chemosensitivity of hypoxic and hypercapnic ventilatory responses (HVR and HCVR) at daytime, although marked oxygen desaturation with sleep apnea was observed. During CMA administration for 7 days, HVR, HCVR and occlusion pressure response to flow-resistive loading were altogether augmented. In one case obstructive sleep apnea (OSA) was altered to obstructive hypopnea, and in the other case central apnea disappeared completely, resulting in remarkable improvement of oxygen desaturation at sleep and daytime somnolence in both cases. We conclude that CMA might be useful in the treatment of sleep apnea syndrome.

Comparison of two synthetic progesterones on ventilation in normal males: CMA vs. MPA

We administered chlormadinone acetate (CMA), medroxyprogesterone acetate (MPA), and placebo to 16 normal male subjects using a randomized double-blind crossover study. After CMA administration, minute alveolar ventilation increased by +1.04 +/- 0.22 (SE) 1/min (P less than 0.05) accompanied by decrements of arterial PCO2 (-4.0 +/- 1.0 Torr) (P less than 0.01) and [HCO3-] (-2.1 +/- 0.05 mM/l) (P less than 0.01). On the other hand, in the MPA runs the corresponding changes of the above parameters were +0.71 +/- 0.21 l/min (P less than 0.05), -2.9 +/- 0.6 Torr (P less than 0.01), and -1.3 +/- 0.3 mM/l (P less than 0.01), respectively. The slopes of hypoxic ventilatory and occlusion pressure response lines remained unchanged in hypocapnia after CMA or MPA ingestion, but they increased when entidal PCO2 was adjusted to the predrug level. The hypercapnic ventilatory and occlusion pressure response lines merely shifted to the left without changing their slopes with these agents. No significant differences in all the above parameters were found between CMA and MPA runs. We concluded that in the normal males the effect of CMA on ventilation was similar to that of MPA, despite the fact that the luteinizing activity of CMA was reported to be approximately 10 times higher than the latter.