| 1. Title: Effect of an oral contraceptive with chlormadinone acetate on depressive mood : analysis of data from four observational studies. Author: Huber JC; Heskamp ML; Schramm GA Source: Clinical Drug Investigation. 2008;28(12):783-91. Abstract: BACKGROUND and objective: Many women of reproductive age experience depressive mood symptoms such as sudden mood swings, irritability, nervousness, excitability and anxiety. Although not defined as a disease, these disturbing mental symptoms are associated with a considerable decrease in quality of life. Molecular pharmacology research over the last 20 years has shown that endogenous steroid hormones may interact with the CNS. Some of these hormones, i.e. the sex hormone progesterone and its 3alpha-reduced metabolites allopregnanolone (3alpha,5alpha-tetrahydroprogesterone) and epipregnanolone (3alpha,5beta-tetrahydroprogesterone, eltanolone), influence mood-balancing and anxiolytic effects via the gamma-aminobutyric acid receptor A (GABA(A)), a major inhibiting receptor of the CNS. Activation of GABA(A) receptor results in mood balancing, anxiolytic, antiepileptic and sedative actions. When oral contraception is considered, it should be taken into account that the various synthetic progestogens used may differ in their influence on mental state. For instance, there is strong clinical evidence of mood-balancing effects for the progesterone derivative chlormadinone acetate (CMA). The aim of these studies was to describe the clinical effects of CMA in combination with ethinylestradiol on depressive mood symptoms. METHODS: Data from four prospective, non-interventional observational studies involving nearly 50 000 women were analysed. The studies documented use of four, six and 12 treatment cycles of the 28-day conventional regimen, as well as providing data on extended cycle regimens. The women in these studies were prescribed CMA 2 mg and ethinylestradiol (EE) 0.03 mg according to gynaecologists' usual practice. RESULTS: Clinical data from the studies confirmed that intake of CMA 2 mg and EE 0.03 mg promotes emotional well-being and reduces mood swings. Improvement in depressive mood was documented after four, six and 12 treatment cycles of the conventional intake regimen as well as with an extended-cycle regimen of CMA/EE. CONCLUSION: CMA 2 mg combined with EE 0.3 mg improves symptoms of depressive mood. The high structural congruence between the endogenous GABA(A) modulator epipregnanolone and the CMA metabolite M-V suggests a direct GABAergic, mood stabilizing function of CMA. We propose a theoretical concept - the CMA-GABA(A) model - that could explain the positive psychotropic effect of CMA. Language: English Keywords: GERMANY | RESEARCH REPORT | DATA ANALYSIS | WOMEN | CHLORMADINONE ACETATE | ORAL CONTRACEPTIVES, SIDE EFFECTS | DEPRESSION | EMOTIONS | ETHINYL ESTRADIOL | CENTRAL NERVOUS SYSTEM EFFECTS | Europe, Central | Europe | Developed Countries | Research Methodology | Demographic Factors | Population | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Safety | Safety | Public Health | Health | Mental Disorders | Diseases | Psychological Factors | Behavior | Contraceptive Agents, Estrogen | Central Nervous System | Physiology | Biology Document Number: 329792 |
2.  Peer Reviewed Title: Efficacy, safety and sustainability of treatment continuation and results of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg chlormadinone acetate, in long-term usage (up to 45 cycles) - an open-label, prospective, noncontrolled, office-based Phase III study. Author: Zahradnik HP; Hanjalic-Beck A Source: Contraception. 2008 May;77(5):337-343. Abstract: This open-label, noncontrolled study assessed the long-term efficacy and tolerability of the monophasic combined low-dose oral contraceptive (OC) ethinyl estradiol (EE) 30 mcg+chlormadinone acetate (CMA) 2 mg (Belara). In total, 781 women who had already taken EE 30 mcg+CMA 2 mg for 24 cycles in a previous Phase III study were assessed for up to 45 cycles. Over 23,033 cycles, the Pearl Index was 0.16 (95% confidence interval, 0.04-0.42). Approximately 86% of women had regular withdrawal bleeding in each cycle, while incidence of intracyclic bleedings (1.6-6.4%) and proportion of women with amenorrhea (4%) were low. The incidence of acne decreased from 13.8% to 5.7%, while rates of hirsutism, alopecia and seborrhea remained low (less than or equal to 4%) throughout this study. The most frequent adverse events were consistent with OC treatment, and no unexpected events occurred. No changes in mean blood pressure and pulse rate were observed during the study, and there were no clinically relevant changes in liver or hematological parameters, hemostasis or carbohydrate metabolism. The incidence of pathological findings in gynecological examination was low and decreased over time. EE 30 mcg+CMA 2 mg was an effective and well-tolerated OC, with beneficial effects on cycle stability, intracyclic bleeding, amenorrhea and signs of androgenization that were maintained during long-term treatment for up to 5 years. There was no evidence of an increased risk of thromboembolic events, atherogenic disease or cervical cancer, suggesting that 30 EE mcg+CMA 2 mg is highly suitable for long-term use. (author's) Language: English Keywords: GERMANY | RESEARCH REPORT | CLINICAL TRIALS | ORAL CONTRACEPTIVES, COMBINED | ETHINYL ESTRADIOL | CHLORMADINONE ACETATE | ADMINISTRATION AND DOSAGE | CONTRACEPTIVE EFFECTIVENESS | CONTRACEPTIVE SAFETY | CONTRACEPTION CONTINUATION | CONTRACEPTIVE AGENTS, SIDE EFFECTS | Europe, Central | Europe | Developed Countries | Clinical Research | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Safety | Public Health | Contraceptive Usage Document Number: 325972 |
| 3. Peer Reviewed Title: Switching hormonal contraceptives to a chlormadinone acetate-containing oral contraceptive. The Contraceptive Switch Study. Author: Schramm G; Heckes B Source: Contraception. 2007 Aug;76(2):84-90. Abstract: 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). 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. 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. 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. (author's) Language: English Keywords: GERMANY | RESEARCH REPORT | PROSPECTIVE STUDIES | WOMEN | CHLORMADINONE ACETATE | ORAL CONTRACEPTIVES | ADMINISTRATION AND DOSAGE | CONTRACEPTIVE METHOD SWITCHING | SIGNS AND SYMPTOMS | MENSTRUAL CYCLE | DYSMENORRHEA | ACNE | Europe, Central | Europe | Developed Countries | Studies | Research Methodology | Demographic Factors | Population | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Methods | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Contraceptive Usage | Diseases | Menstruation | Reproduction | Menstruation Disorders | Dermatitis Document Number: 318906 |
| 4. Peer Reviewed Title: Pharmacokinetics of chlormadinone acetate following single and multiple oral dosing of chlormadinone acetate (2 mg) and ethinylestradiol (0.03 mg) and elimination and clearance of a single dose of radiolabeled chlormadinone acetate. Author: Terlinden R; Uragg H; Gohler K; Kneip C Source: Contraception. 2006 Sep;74(3):239-244. Abstract: Published data on pharmacokinetic parameters for chlormadinone acetate (CMA) are in part contradictory, especially with regard to terminal half-life (t/1/2,z). Single and multiple doses of CMA (2 mg) and ethinylestradiol (EE; 0.03 mg) were administered to healthy female volunteers for six menstrual cycles. Plasma concentrations of CMA and EE were determined by gas chromatography--mass spectrometry. Single-dose and steady-state pharmacokinetic parameters were calculated. In a separate study, healthy female volunteers were given a single 2-mg dose of radiolabeled CMA. Concentrations of radioactivity in fecal and urine samples were determined via liquid scintillation. Excretion of total radioactivity was calculated as percentage of administered dose. Eighteen women completed the repeated-dose study. Peak plasma concentrations for CMA and EE were reached within 1 and 2 h after taking the study drug. Peak plasma concentrations of CMA were ~1600 pg/mL after single-dose administration and 2000 pg/mL after multiple dosing. CMA and EE showed linear pharmacokinetics throughout six cycles, with constant trough values of ~400--500 pg/mL for CMA and 20--40 pg/mL for EE. Mass balance factors were 1.2--1.4 for CMA and 1.6--1.7 for EE, and accumulation factors were 1.7--2 for CMA and 1.7--1.8 for EE. Mean t1/2,z of CMA was approximately 25 h after single dosing and 36--39 h at steady state. In the excretion balance study, mean dose of CMA recovered was 87.3 ± 6.4%, with urinary and fecal excretion accounting for 45% and 42%, respectively. The pharmacokinetics of CMA and EE is linear after multiple dosing and remains stable during long-term administration, once steady state is reached. The t/1/2,z of CMA was 36--39 h after multiple dosing, which is considerably shorter than the 80 h often quoted in the literature. (author's) Language: English Keywords: GERMANY | RESEARCH REPORT | WOMEN | HUMAN VOLUNTEERS | ORAL CONTRACEPTIVES, COMBINED | CHLORMADINONE ACETATE | ETHINYL ESTRADIOL | ADMINISTRATION AND DOSAGE | METABOLIC EFFECTS | EVALUATION | Developed Countries | Europe, Central | Europe | Demographic Factors | Population | Clinical Research | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Estrogen | Drugs | Treatment | Medical Procedures | Medicine | Health Services | Delivery of Health Care | Health | Physiology | Biology Document Number: 304454 |
| 5. Title: Human resource management assessment tool. Author: Family Planning Management Development. Management Sciences for Health [MSH] Source: The Manager. 1999;8(1):[18] p.. Abstract: This supplement to The Manager provides a tool for assessing an organization’s Human Resource Management (HRM) system--what is consists of and how well it is functioning. The HRM Assessment Tool helps uses to develop strategies to improve the human resource system and make it as effective as possible. It can also serve as a basis for focusing discussions, brainstorming, and strategic planning. It is designed to be used in public and private-sector health organizations. (excerpt) Language: English Keywords: NEW ZEALAND | RESEARCH REPORT | CLINICAL TRIALS | WOMEN | ETHINYL ESTRADIOL | CHLORMADINONE ACETATE | LEVONORGESTREL | ADMINISTRATION AND DOSAGE | CONTRACEPTIVE EFFECTIVENESS | LIPID METABOLIC EFFECTS | METABOLIC EFFECTS | SIDE EFFECTS | Oceania | Developed Countries | Clinical Research | Research Methodology | Demographic Factors | Population | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Drugs | Treatment | Lipids | Physiology | Biology Document Number: 284439 |
| 6. Title: Efficacy and safety of the new antiandrogenic oral contraceptive Belara. Author: Zahradnik HP; Goldberg J; Andreas JO Source: CONTRACEPTION. 1998 Feb;57(2):103-9. Abstract: The contraceptive safety and efficacy of long-term use of the oral contraceptive Belara (30 mcg ethinyl estradiol and 2 mg chlormadinone acetate) were assessed in an open, noncontrolled phase III study. Of particular interest was the effect of the anti-androgenic activity of this formulation on clinical signs of androgenization. Belara was taken by 1655 German women (mean age, 25.9 years), for a total of 22,337 cycles. A total of 12 pregnancies occurred, yielding a theoretical Pearl index of 0.269 (95% confidence interval, 0.109-0.600). No withdrawal bleeding occurred in 1655 cycles (7.4%), while spotting was documented in 2565 (11.5%) and breakthrough bleeding in 786 (3.5%). After 12 cycles of use, acne on the face/neck improved in 64.1% of affected women and completely disappeared in 53.4%. Seborrhea improved after 12 cycles in 67.9% of affected women and was cured in 58.0%. Side effects included headache (37.4%), nausea (23.1%), breast tenderness (21.7%), and vaginal discharge (19.4%). Of the 62 serious adverse events reported by 59 women, only the 2 cases of deep venous thrombosis could be linked to Belara use. Overall, these findings suggest that Belara is a well-tolerated oral contraceptive with minor side effects comparable to those associated with use of other low-dose pills. Language: English Keywords: GERMANY | RESEARCH REPORT | CLINICAL RESEARCH | ORAL CONTRACEPTIVES, LOW-DOSE | CHLORMADINONE ACETATE | MENSTRUATION DISORDERS | CONTRACEPTIVE EFFECTIVENESS | ACNE | SIDE EFFECTS | PREVENTION AND CONTROL | ORAL CONTRACEPTIVES, SIDE EFFECTS | Europe, Central | Europe | Developed Countries | Research Methodology | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Diseases | Dermatitis | Treatment | Contraceptive Safety | Safety | Public Health | Health Document Number: 132990 |
| 7. Title: [Antiovulatory action of chlormadinone acetate] Action anti-ovulatoire de l'acetate de chlormadinone. Author: Pelissier C; Blacker C; Feinstein MC; Cournot A; Denis C Source: Contraception, Fertilite, Sexualite. 1994 Jan;22(1):37-40. Abstract: The antiovulatory action of chlormadinone acetate was studied in six healthy volunteers who were given two daily doses of 5 mg each from the seventh to the twenty-fifth cycle day. Chlormadinone acetate is of potential interest as a contraceptive method for the small group of women with contraindications to synthetic estrogens and norsteroid progestins for whom no other methods are acceptable. The observation period included four cycles: a control cycle before treatment during which ovulation was confirmed, two treatment cycles, and an observation cycle after treatment. Antiovulatory action was assessed by daily determination of plasma FSH, LH, estradiol, and progesterone levels. The results confirmed the antiovulatory action of chlormadinone acetate and revealed no clinical signs of functional ovarian cysts or premenstrual syndrome. In all cases, the LH surge observed in the control cycle was blunted by chlormadinone acetate, while the base gonadotropin levels were not modified. Hormonal profiles in the second treatment cycle showed no preovulatory gonadotropin surge and no significant progesterone secretion. Estradiol production was variable through midcycle and then low normal in all subjects. In the last cycle week, the estradiol level was below 50 pg/ml in two cases and between 50 and 100 pg/ml in the others. In five cases out of six, the level of progesterone was 1 ng/ml or lower. In the sixth case, the data were incompatible with ovulation. Cycle tolerance was good and ovarian function returned during the first posttreatment cycle. No significant variation in weight or blood pressure was observed at the end of the second treatment cycle. Language: French Keywords: FRANCE | PROSPECTIVE STUDIES | CLINICAL RESEARCH | HUMAN VOLUNTEERS | CHLORMADINONE ACETATE | CONTRACEPTIVE AGENTS, PROGESTIN | OVULATION SUPPRESSION | WOMEN | Europe, Western | Europe | Developed Countries | Studies | Research Methodology | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Mode of Action | Demographic Factors | Population Document Number: 097526 |
| 8. Title: [High-dose progestational contraception: advantages] Contraception macroprogestative: avantages. Author: Jamin C Source: Contraception, Fertilite, Sexualite. 1993 Feb;21(2):123-8. Abstract: Benefits of high-dose progestational contraception (pregnanes [chlormadinone acetate] or norpregnanes, promegestone, nomegestrol acetate) are its anti-estrogenic effect and its overall absence of metabolic effects. It lowers apoprotein A1 and increases antithrombin 3, but these changes produce no adverse effects. High-dose progestational contraception is ideal for women with certain contraindications to combined oral contraceptive use: high blood pressure, hyperlipemia, diabetes mellitus, benign breast disease, and premenstrual tension. It inhibits ovulation. Nomegestrol acetate also changes the cervical mucus, making it inhospitable to sperm. The primary side effect of high-dose progestational contraception is menstrual cycle disturbances. A study of 5 mg nomegestrol acetate among women aged 19-40 used for 20 days of each 28 day cycle revealed no pregnancies. A preliminary study shows that transdermal administration of nomegestrol acetate and estradiol 17 beta adequately treats hypoestrogeny. In conclusion, high-dose progestational contraception produces excellent metabolic results and reduces clinical manifestations of hyperestrogeny. Language: French Keywords: LITERATURE REVIEW | CONTRACEPTIVE AGENTS, PROGESTIN | METABOLIC EFFECTS | CHLORMADINONE ACETATE | CONTRACEPTIVE MODE OF ACTION | MENSTRUATION DISORDERS | ESTRADIOL | ADMINISTRATION AND DOSAGE | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Physiology | Biology | Diseases | Estrogens | Hormones | Endocrine System | Drugs | Treatment Document Number: 104218 |
| 9. Peer Reviewed Title: Combined oral contraceptives containing chlormadinone acetate and breast cancer: results of a case-control study. Author: Ebeling K; Ray R; Nischan P; Thomas DB; Kunde D; Stalsberg H Source: BRITISH JOURNAL OF CANCER. 1991 May;63(5):804-8. Abstract: The main subject of this hospital-based case-control study was the potential relationship between use of combined oral contraceptives (OCs) containing chlormadinone acetate (CA) and breast cancer. Analyses were performed for combined OCs with and without CA. For either of the combined OCs, risk was not elevated in ever users, it did not increase with the duration of use, and it did not change with time since the initial exposure or with time since most recent use. However, the relative risk was increased in current users---RR=1.72 (0.88, 3.36) for combined OCs with CA and RR=1.42 (1.01, 2.00) for combined OCs without CA which is explained as a screening effect. These results demonstrate that CA as a constituent of combined OCs does not influence breast cancer risk. (author's modified) Language: English Keywords: GERMANY | CASE CONTROL STUDIES | RISK FACTORS | AGE FACTORS | VALIDITY | ORAL CONTRACEPTIVES, COMBINED | BREAST CANCER | CHLORMADINONE ACETATE | SIDE EFFECTS | ORAL CONTRACEPTIVES, SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | Europe, Central | Europe | Developed Countries | Studies | Research Methodology | Biology | Population Characteristics | Demographic Factors | Population | Measurement | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Cancer | Neoplasms | Diseases | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Treatment | Contraceptive Safety | Safety | Public Health | Health Document Number: 067864 |
| 10. Title: [Contraceptives and systemic lupus erythematosus. Answer to question] Kontrazeptiva und Lupus erythematodes systematisatus. Author: Wagner J; Andrassy K Source: HAUTARZT. 1991 Nov;42(11):726. Abstract: Systemic lupus erythematosus (SLE) affects mostly women in reproductive age; therefore, pregnancy is always a risk with SLE. In about 30-50% of women with lupus during pregnancy and/or the early postpartum period an exacerbation of the disease occurs. There is increased risk of spontaneous abortion, premature birth, and miscarriage, especially in the 3rd trimester. It is not necessary to dissuade such patients from having children, but they must be aware of the risks involved. Contraceptives for mostly young women with SLE must be safe, reliable, and devoid of any effects on the disease. Estrogens, especially ethinyl estradiol, can trigger the outbreak of a latent disease even in low dosages; therefore, they should be avoided in SLE patients. In a prospective study of women with lupus nephropathy, a 3-month use of ethinyl estradiol resulted in activation of SLE in 43% of them, while it failed to be triggered in patients undergoing progesterone therapy in the course of a 30-month observation period. Pure progesterone derivatives, such as chlormadinone, are practically free of side effects that intensify vasculitis; thus, they can be recommended as the safest, routine method of oral contraception for SLE patients. In addition, the IUD could also be considered because of the possible influence medicaments exert on the disease. Often adnexitis can be expected because of the diminished defensive capacity of SLE patients, whereby infection-dependent stimulation of the immune system can lead to exacerbation of SLE. Language: German Keywords: SYSTEMIC LUPUS ERYTHEMATOSUS | PREGNANCY COMPLICATIONS | ABORTION, SPONTANEOUS | PREMATURE BIRTH | CONTRACEPTIVE AGENTS, ESTROGEN | ETHINYL ESTRADIOL | CHLORMADINONE ACETATE | ADNEXAL EFFECTS | RISK FACTORS | WOMEN | CONTRAINDICATIONS | Diseases | Pregnancy Outcomes | Pregnancy | Reproduction | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Genital Effects, Female | Genitalia, Female | Genitalia | Urogenital System | Physiology | Biology | Demographic Factors | Population | Treatment Document Number: 076100 |
| 11. Peer Reviewed Title: [Effects of Sequostat as compared to Sequenz-Ovosiston on selected metabolic parameters] Wirkung von Sequostat im Vergleich zu Sequenz-Ovosiston auf ausgewahlte Parameter des Stoffwechsels. Author: Etzrodt R; Klinger G; Carol W Source: ZENTRALBLATT FUR GYNAKOLOGIE. 1990;112(8):489-96. Abstract: The effects of 2 sequential oral contraceptives (OCs), Sequostat (6 days ethinyl estradiol 0.05 mg, 15 days ethinyl estradiol 0.05 mg + norethisterone acetate 1.0 mg) and Sequenz-Ovosiston (9 days mestranol 0.1 mg, 12 days mestranol 0.08 mg + chlormadinone acetate 2.0 mg), on triglycerides, total cholesterol, HDL and LDL cholesterol, glucose tolerance, total plasma proteins, plasma protein fractions, plasma transaminases, gamma-glutamyl-transferase, alkaline phosphatase, and antithrombin III were studied in 2 groups of women (total=75 women). Investigations were performed prior to the hormonal intake and after treatment for 3, 6, and 12 months. SIgnificant but minimal changes were noted across all parameters; however, Sequenz-Ovosiston exerted less of an effect on glucose tolerance. A significant increase in HDL cholesterol and a reduction in the LDL/HDL cholesterol relation was demonstrated during the 1st 6 months, which was the result of estrogen dominance in the OCs. (author's modified) (summaries in GER, ENG) Language: German Keywords: ORAL CONTRACEPTIVES, PHASIC | ETHINYL ESTRADIOL | NORETHINDRONE ACETATE | MESTRANOL | CHLORMADINONE ACETATE | LIPID METABOLIC EFFECTS | CHOLESTEROL | GLUCOSE TOLERANCE TEST | PLASMA PROTEIN BINDING CAPACITY | SIDE EFFECTS | CHANGES | ORAL CONTRACEPTIVES, SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | Oral Contraceptives, Combined | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Norethindrone | Contraceptive Agents, Progestin | Lipids | Physiology | Biology | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Hemic System | Treatment | Social Change | Contraceptive Safety | Safety | Public Health | Health | Demographic Factors | Population Document Number: 064403 |
| 12. Title: [Characteristics of estrogens and gestagens] Charakteristik der Estrogene und Gestagene. Author: Goretzlehner G; Kohler G Source: ZEITSCHRIFT FUR ARZTLICHE FORTBILDUNG. 1990;84(1-2):7-12. Abstract: The most important synthetic orally effective estrogens are ethinyl estradiol (EE) and mestranol as well as the depot testrogens, quinestrol, and turisteron. 1.1.5 mg of EE and 1.5-2.0 mg of mestranol are the minimal proliferation doses of a quiescent endometrium within 14 days, while the ovulation inhibition dose of EE is .7 mg between the 5th and 15th days of menstruation. In 1-phase preparations, 20 mcg of EE is used, and in sequential pills, 50 mcg of EE is used. Low doses have diminished the stability of the menstrual cycle, increased spotting, and rushed ovulation. Micropills contain <50 mcg of EE, medium-dose pills contain 50 mcg of EE, and high-dose pills contain >50 mcg of EE. THe average dose of mestranol is 80 mcg. The first 2-phase preparations (sequential pills) were followed by normo-phasic pills: gestagen taken from the 8th day in addition to estrogen. Estrogen-gestagen combination and normo-phasic pills protect against endometrial carcinoma. Weekly pills (Deposition) are taken once a week: 1 pill containing 1 mg of EE for 3 weeks followed by 10 mg of norethisterone acetate on the 4th weeks. Usually, hormonal withdrawal bleeding ensues 2-3 days after gestagen application. The Pearl Index value is 1-2. EE sulfonate therapy is recommended for no longer than 2 years because of the risk of hyperplasia of the endometrium. 4-5 mg of quinestrol (3-cyclopentylether of EE) is used as a once-a-month pill with chlormadinone acetate, norethisterone acetate (NEA), quingestanol, or levonorgestrel (LNG) taken on the 25th day of the cycle. Synthetic gestagens consist of progesterone derivatives (retroprogesterones, 17-hydroxyprogesterone) and of testosterone derivatives (19-nortestosterone, 3-desoxy-19-nortestosterone). They cause the secretional transformation of a proliferated endometrium. The bioavailability of micronized pills is greater: the transformation dose of LNG is 5-6 mg, and of micronized LNG it is 2.5 mg. Chlormadinoacetate (CMA), a 17-alpha-hydroxyprogesterone derivative, is injected sc in fatty tissue. CMA is antiandrogenic, and after 3 days only 17% is excreted in the urine and stool. 50-60% of NEA is bioavailable when taken orally, 50-70% of it is excreted in the urine after 4 days, and 30-40% is eliminated in the stool. LNG is a very strong gestagen and antiestrogen reaching the highest concentration 1-2 hours after ingestion. By replacing sex hormone binding globulin bound testosterone, it is slightly androgenic. The maximum serum level of dienogest (DNG) is reached 1-2 hours after administration. DNG is anti-androgenic; it does not cumulate, but wide fluctuations of plasma levels cause bleeding. Language: German Keywords: GERMANY | CRITIQUE | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | ORAL CONTRACEPTIVES, LOW-DOSE | HORMONES | CONTRACEPTIVE AGENTS, ESTROGEN | ETHINYL ESTRADIOL | MESTRANOL | CONTRACEPTIVE MODE OF ACTION | CHLORMADINONE ACETATE | QUINGESTANOL ACETATE | CONTRACEPTIVE AGENTS, PROGESTIN | Europe, Central | Europe | Developed Countries | Oral Contraceptives | Contraceptive Methods | Contraception | Family Planning | Endocrine System | Physiology | Biology | Contraceptive Agents, Female | Contraceptive Agents Document Number: 062901 |
| 13. Title: [Oral contraception and systemic lupus erythematosus (SLE)] Contraception hormonale et lupus. Author: Jungers P; Liote F; Dehaine V; Dougados M; Viriot J; Pelissier C; Kuttenn F Source: ANNALES DE MEDECINE INTERNE. 1990;141(3):253-6. Abstract: The choice of an optimal contraceptive method is a significant problem in female SLE patients. In view of the influence of sex hormones on the evolution of SLE, oral contraceptive (OC) therapy has to be efficient, reversible and safe, without aggravation to the already-present condition, and must not cause metabolic and vascular side effects. Ethinyl estradiol-containing preparation, even at 30 mcg/day, have been shown to trigger a crisis or unmask SLE, and they exert adverse metabolic and vascular effects. Therefore, combination estrogen- progestogen OCs do not stimulate SLE activity, but norsteroids have harmful metabolic side effects and microprogesterones are not sufficiently reliable. In light of the decreased level of plasma androgens in female SLE patients, an attempt to modulate the hormonal milieu by lowering the estrogen-to-androgen ratio, while ensuring contraception, was attempted using cyproterone acetate. This agent markedly lower and plasma estrogens and was effective and well- tolerated, but its longterm on bone mineralization remains to be evaluated. Chlormadinone acetate, a 17-OH progesterone derivative, was proven effective and devoid of any metabolic or vascular side effects, and should be recommended as the safest routine OC therapy in women with SLE. (author's modified) (summaries in FRE, ENG) Language: French Keywords: ORAL CONTRACEPTIVES, SIDE EFFECTS | SYSTEMIC LUPUS ERYTHEMATOSUS | CHLORMADINONE ACETATE | CONTRACEPTIVE METHODS | SIDE EFFECTS | Contraceptive Safety | Safety | Public Health | Health | Diseases | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Treatment Document Number: 062519 |
| 14. Title: Pharmacokinetics of oestrogens and progestogens. Author: Kuhl H Source: MATURITAS. 1990 Sep;12(3):171-97. Abstract: There are large inter- and intraindividual variations in the serum concentrations of natural and synthetic sex steroids irrespective of the route of administration. Oral intake of steroids has a stronger effect on hepatic metabolism than parenteral administration, as the local concentration in liver sinusoids are 4-5 times higher during the 1st liver passage. Estradiol and estrone are interconvertible, dependent on the local concentrations in liver and target organs, and estrone sulphate serves as a large reservoir. The estrone/estradiol ratio has no physiological significance, as estrone is only a weak estrogen. Estrone is both a precursor and a metabolite of estradiol. Estriol is extensively conjugated after oral administration. Therefore, the estriol serum levels are similar after oral intake of 10 mg and after vaginal application of 0.5 mg estriol resulting in similar systemic effectiveness. Conjugated estrogens can easily enter the hepatocytes but are hormonally active only after hydrolyzation into the parent steroids. Ethinyl estradiol which exerts strong effects on hepatic metabolism and inhibits metabolizing enzymes should not be used for hormone replacement therapy. Among the progestogens, the progesterone derivatives have less effects on liver metabolism than the norethisterone derivatives (13-methyl-gonanes and 13-ethyl-gonanes). The highly potent 13-ethyl-gonanes are effective at very low doses, because of a slow inactivation and elimination rate due to the ethinyl group. (author's) Language: English Keywords: ESTROGENS | PROGESTERONE | ESTRADIOL | ESTRONE | ESTRIOL | MEASUREMENT | STEROID METABOLIC EFFECTS | LABORATORY EXAMINATIONS AND DIAGNOSES | ETHINYL ESTRADIOL | LEVONORGESTREL | ETHYNODIOL DIACETATE | LYNESTRENOL | NORETHINDRONE | CYPROTERONE ACETATE | CHLORMADINONE ACETATE | NORETHINDRONE ACETATE | ANALYSIS | Hormones | Endocrine System | Physiology | Biology | Progestational Hormones | Research Methodology | Metabolic Effects | Examinations and Diagnoses | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Progestin | Hormone Antagonists Document Number: 064558 |
| 15. Title: Risks of estrogens and progestogens. Author: L'Hermite M Source: MATURITAS. 1990 Sep;12(3):215-46. Abstract: The risks and benefits of specific types of postmenopausal estrogens and progestogens are explored: those affecting serum lipids, clotting elements, hepatic proteins synthesis, blood pressure, glucose tolerance, endometrial, breast and cervical cancer. Ethinyl estradiol taken orally is the only estrogen likely to cause gall bladder disease. It also induces liver protein synthesis when taken orally or vaginally. Natural estrogens do not heighten coagulation factors, and may shift towards fibrinolysis. Both ethinyl estradiol and equine estrogens may increase blood pressure, while natural estrogens may decrease it. Similarly natural estrogens induce prostacyclin synthesis, while ethinyl estradiol activates both prostacyclin and thromboxanes. Progestagens, especially so the norprogestins, disturb carbohydrate metabolism and tend to reverse the beneficial effects of estrogens on serum lipids, a 40-70% reduction in risk of mortality from coronary heart disease. A meta- analysis of 23 studies concluded that menopausal estrogens do not increase the risk of breast cancer by a measurable degree, except in high doses and in those predisposed by family history. There is an increased risk of endometrial carcinoma for those taking unopposed estrogens for more than 3-6 years. This can be attenuated by taking combined estrogen-progestins, which will eventually result in absence of bleeding, or a 12-day progestogen course every 4-6 cycles. Oral micronized progesterone decreases blood pressure. The relative androgenic effects of progestins other than the norprogesterone derivatives are less significant. As an alternative to taking a progestogen, a woman could have regular endometrial sampling or abdominal or vaginal sonograms to detect endometrial cancer. Language: English Keywords: LITERATURE REVIEW | MENOPAUSE | ESTRADIOL | ESTRIOL | ESTRONE | CONJUGATED ESTROGENIC SUBSTANCES | CHLORMADINONE ACETATE | ETHINYL ESTRADIOL | MEDROXYPROGESTERONE ACETATE | LEVONORGESTREL | LYNESTRENOL | NORETHINDRONE | GALLBLADDER DISEASES | CARDIOVASCULAR EFFECTS | CEREBROVASCULAR EFFECTS | HYPERTENSION | THROMBOEMBOLISM | SERUM PROTEIN EFFECTS | GLUCOSE METABOLISM EFFECTS | LIPID METABOLIC EFFECTS | BREAST CANCER | ENDOMETRIAL CANCER | MORTALITY | RISK FACTORS | DESOGESTREL | GESTODENE | NORGESTIMATE | CYPROTERONE ACETATE | WOMEN | Reproduction | Estrogens | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Diseases | Vascular Diseases | Embolism | Hematological Effects | Hemic System | Carbohydrate Metabolic Effects | Metabolic Effects | Lipids | Cancer | Neoplasms | Population Dynamics | Demographic Factors | Population | Hormone Antagonists Document Number: 064559 |
| 16. Title: Clinical use of oestrogens and progestogens. Author: Lauritzen C Source: MATURITAS. 1990 Sep;12(3):199-214. Abstract: The clinical use of estrogens and progestogens for menopausal women is reviewed, discussing the indications, results of studies on effectiveness of various agents o each target organ, contraindications, risk-benefit ratio, and types of drug preparations available and used in European countries. The indications for menopausal hormone replacement are primarily to prevent myocardial infarction and osteoporosis, and also to treat early menopause, urogenital atrophy, and severe skin, mucous membrane and psychic disorders. Mechanisms of action of estrogens and progestins, and anticipated results are detailed for each of the indications. Contraindications typical of oral contraceptives usually do not apply for hormone replacement. For example, only severe acute liver disease, current thromboembolism, endometrial cancer other than I, and breast cancer within 3-5 years of primary treatment are contraindications. Neither cervical, ovarian or vulvar cancer, diabetes, varicose veins, hypertension, nor history of liver disease or thromboembolism are contraindications: in some cases progestins or transdermal estrogens are recommended. Estrogen side effects suggest overdosage. Progesterone or its derivatives rather than oral contraceptive progestins are prescribed. There is a clear benefit, comparing cost of medication to that of treating consequences of estrogen deficiency. The preparations currently used in Europe include oral micronized estradiol, conjugated estrogens, transdermal patches, local vaginal estrogens, and injectable estradiol esters for those who cannot tolerate oral or transdermal agents. Preparations should contain progesterone unless the woman has had a hysterectomy. Combinations designed to avoid withdrawal bleeding are available. Language: English Keywords: GERMANY | EUROPE | LITERATURE REVIEW | DECREASED LIBIDO | ESTRADIOL | ESTRONE | CONJUGATED ESTROGENIC SUBSTANCES | PROGESTERONE | ESTRIOL | MEDROXYPROGESTERONE ACETATE | CHLORMADINONE ACETATE | PROGESTATIONAL HORMONES | NORETHINDRONE ACETATE | LYNESTRENOL | LEVONORGESTREL | MENOPAUSE | MIDDLE AGED ADULTS | MYOCARDIAL INFARCTION | VAGINAL ABNORMALITIES | ORAL CONTRACEPTIVES | INJECTABLES | TREATMENT | MEDICINE | Europe, Central | Developed Countries | Sex Behavior | Behavior | Estrogens | Hormones | Endocrine System | Physiology | Biology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Norethindrone | Reproduction | Adults | Age Factors | Population Characteristics | Demographic Factors | Population | Heart Diseases | Diseases | Contraceptive Methods | Health Services | Delivery of Health Care | Health Document Number: 064557 |
| 17. Title: [To prescribe for the diabetic: a contraceptive method] Prescrire chez la diabetique: une contraception. Author: Buchsenschutz D Source: GAZETTE MEDICALE. 1989 Jan 27-Feb 2;96(4):25-31. Abstract: Although careful planning of pregnancies is of utmost importance for diabetic women, recent surveys have shown that a high proportion of diabetic women use less reliable or no contraceptive method. The contraceptive method should be reliable, safe, and comfortable, and should not aggravate vascular risks. Synthetic estrogens increase the need for insulin in insulin-dependent diabetics, elevate blood sugar levels in noninsulin-dependent diabetics, and can precipitate diabetes in predisposed women. Combined oral contraceptives (OCs) are thus formally contraindicated except in very exceptional cases for brief periods in insulin-dependent diabetics with no other complications or vascular risk factors. Low-dose progestins have no effects on the vascular system or glucose metabolism, but they must be taken at the same time every day and they frequently cause menstrual disturbances. They are less effective than conventional OCs and are associated with higher rates of extrauterine pregnancy and functional ovarian cysts. In most cases functional ovarian allowing surgery to be avoided. Low-dose progestins are not recommended in case of benign breast disorders, and their efficacy many be lessened by interaction with certain other drugs. High-dose progestins administered for 20 days beginning on the 6th cycle day are effective and provide regular cycles. Progesterone derivatives are preferred. Chlormadinone acetate has been most commonly used for several years and appears will tolerated for short or medium term use in insulin dependent and noninsulin-dependent diabetics. High-dose progestins are sensitive to drug interactions. They should be avoided in diabetics with severe microangiopathy. The IUD is an excellent choice for diabetic women with at least 1 child. The failure rate does not seem to be increased by the diabetes, and infections are no more likely if the recommendations for follow-up are respected. The absolute contraindications are the same as those for nondiabetic women: nulliparity, history of salpingitis, existence of leucorrhea possibly signalling infection,and seropositivity for chlamydia. Barrier methods are less effective than hormonal methods and the IUD, but are useful as temporary replacements or if the couple prefers them. The "morning after" pill can be used in exceptional circumstances but requires adjustment of the insulin dose. So-called natural methods should be avoided due to their high failure rates. Tubal ligation is appropriate for older diabetics and those for whom future pregnancies are medically inadvisable. Contraceptive follow-up for diabetics using OCs and IUDs should be twice yearly or more often. Diabetic women should be fully informed about the proper use, possible side effects, and problems requiring immediate medical attention of their methods. Language: French Keywords: FRANCE | DIABETES | CONTRACEPTIVE METHODS | RISK ASSESSMENT | CONTRACEPTIVE AGENTS, ESTROGEN | LOW-DOSE PROGESTINS | CHLORMADINONE ACETATE | CONTRACEPTIVE AGENTS, PROGESTIN | IUD | BARRIER METHODS | NATURAL FAMILY PLANNING | TUBAL LIGATION | CONTRAINDICATIONS | TUBAL OCCLUSION | Europe, Western | Europe | Developed Countries | Diseases | Contraception | Family Planning | Evaluation | Contraceptive Agents, Female | Contraceptive Agents | Family Planning, Behavioral Methods | Female Sterilization | Sterilization, Sexual | Treatment Document Number: 066399 |
| 18. Title: Oral contraceptives: significance of their effects in man and relationship to findings in animal models. Author: Pasquale SA Source: TOXICOLOGIC PATHOLOGY. 1989;17(2):396-400. Abstract: A historical review of the 28-year history of oral contraceptives from the viewpoint of correlation or lack thereof between drug toxic and pathologic effects seen in laboratory animals and those seen clinically is presented. Early high dose pills were expected to cause growth of uterine fibroids, but instead they had the unexpected effect of an estrogen dose-related venous thrombosis risk. Work on rats predicted that pills would cause liver cancers, but instead to slightly increase the incidence of being liver adenomas in women. Similarly, rat research predicted pituitary microadenomas. Pituitary effects in women, while rare, are thought to be due to prescription of pills to women with irregular cycles of pituitary origin. Progestins of the 17-acetoxy series were considered likely to produce breast cancers, as they had in beagle dogs. They apparently have not done so in women. They were reports in the mid-1970s that sequential pills containing 100 mcg ethinyl estradiol cause endometrial carcinoma. These pills have been discontinued. Recent evidence has been accumulating that low-dose pills containing levonorgestrel increase blood pressure and possible LDL-cholesterol. Risk of death from vascular disease, however, seems to be concentrated in women who smoke, especially those over 35. Language: English Keywords: UNITED STATES OF AMERICA | LITERATURE REVIEW | HISTORICAL REVIEW | ORAL CONTRACEPTIVES | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES, PHASIC | CHLORMADINONE ACETATE | MESTRANOL | LEVONORGESTREL | CONTRACEPTIVE AGENTS, FEMALE | NORETHYNODREL | NORETHINDRONE | CARDIOVASCULAR EFFECTS | HYPERTENSION | THROMBOEMBOLISM | LIVER NEOPLASMS | LIPID METABOLIC EFFECTS | BREAST CANCER | FIBROIDS | PITUITARY GLAND | LABORATORY ANIMALS | COMPARATIVE STUDIES | Developed Countries | North America | Americas | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents | Contraceptive Agents, Estrogen | Physiology | Biology | Vascular Diseases | Diseases | Embolism | Neoplasms | Lipids | Cancer | Neoplasms, Benign | Endocrine System | Clinical Research | Research Methodology | Studies Document Number: 060515 |
| 19. Title: [Contraception in women with systemic lupus erythematosus] Contraception chez la femme lupique. Author: Gompel A; Kuttenn F; Mauvais-Jarvis P Source: ANNALES DE DERMATOLOGIE ET DE VENEREOLOGIE. 1988;115:367-72. Abstract: The hormonodependence of systemic lupus erythematosus is indicated by its greatest prevalence in fertile aged women and the probable aggravating effect of pregnancy and combined oral contraceptives (OCs) on it. Contraception for women with lupus must be as effective as possible without thromboembolic or metabolic effects, and must be compatible with treatments for lupus, especially corticotherapy. It must not expose the patient to an attack for example through infection. Combined OCs are absolutely contraindicated because of their estrogen content and vascular risks, while high dose norsteroid progestin only pills are contraindicated because of their thromboembolic and metabolic risks. IUDs are inadvisable because corticotherapy may diminish their efficacy, and because of the significant risk of infection. Low dose norsteroid progestins are possible, but because of their incomplete blockage of ovulation they are associated with erratic and sometimes considerable levels of endogenous estradiol which are undesirable in women with lupus. Such ovarian dystrophies also cause breast and pelvic pain which limit their use. The efficacy of low dose progestins is not total and may be reduced by some drug interactions, especially with enzymatic inductors. They do however appear to be without significant vascular effects. Of the 4 such products available, pills containing norgestrienone appear the best tolerated. 2 derivatives of 17-hydroxyprogesterone, chlormadinone acetate and cyproterone acetate, can be used. Chlormadinone acetate has an incomplete and incompletely studied antigonadotropic effect, but endometrial atrophy is rapid and may cause spotting. Its effectiveness may be reduced by enzymatic inductors. It does not modify lipid metabolism or blood pressure, has no anabolizing effect, and does not modify coagulation. Cyproterone acetate has been shown to have excellent metabolic and vascular tolerance. At a dose of 50 mg, it has a complete antigonadotropic effect after 2 months, which gives it complete contraceptive efficacy. An initial study in women with lupus showed good tolerance and clinical improvement, and a larger study is now underway. Luteinizing hormone releasing hormone analogs do not appear appropriate for longterm use but may perhaps be useful in advanced cases of lupus when a hypoestrogenic state could be beneficial. Among nonchemical methods, only diaphragms with spermicides appear sufficiently effective for women with lupus. Condoms are possible but less effective. Tubal ligation is desirable if the desired or permitted family size has been attained. Language: French Keywords: SYSTEMIC LUPUS ERYTHEMATOSUS | DERMATOLOGICAL EFFECTS | DISEASES | HIGH RISK WOMEN | ORAL CONTRACEPTIVES, COMBINED | ORAL CONTRACEPTIVES | CONTRACEPTIVE AGENTS, PROGESTIN | LOW-DOSE PROGESTINS | ORAL CONTRACEPTIVES, LOW-DOSE | CONTRACEPTIVE AGENTS, FEMALE | IUD | BARRIER METHODS | CONTRACEPTION | FEMALE STERILIZATION | STERILIZATION, SEXUAL | FAMILY PLANNING | CHLORMADINONE ACETATE | HORMONES | CYPROTERONE ACETATE | HORMONE ANTAGONISTS | REPRODUCTIVE CONTROL AGENTS | CONTRAINDICATIONS | Physiology | Biology | Reproduction | Contraceptive Methods | Contraceptive Agents | Endocrine System | Treatment Document Number: 054818 |
| 20. Title: [The effect of ethynyl estradiol sulfonate alone and in combination with five different gestagen preparations on selected lipid and lipoprotein parameters in young women] Der Einfluss von Ethinylestradiolsulfonat allein und in Kombination mit funf verschiedenen Gestagenpraparaten auf ausgewahlte Lipid- und Lipoproteinparameter bei jungen Frauen. Author: Oswald B; Klinger G; Schubert W Source: ZENTRALBLATT FUR PHARMAZIE, PHARMAKOTHERAPIE UND LABORATORIUMS DIAGNOSTIK. 1988;127(11):727-30. Abstract: 114 women aged 16 to 20 were investigated on one occasion or 1st prescription of contraceptives to measure the effect of gestagens on lipoprotein mechanism involved in atherosclerosis. The 1st control group received no contraceptives, the 2nd control group received 1 mg each of ethinyl estradiol sulfonate (EES) on the 2nd, 10th, and 16th day of the cycle, and the other groups received from the 10th to the 20th day a daily dose of .5 mg levonorgestrel (NG), .3 mg of desogestrel (DG), 2 mg of dienogest (STS, 5 mg of norethisteroneacetate (NOR), or 4 mg of chlormadinoneacetate (CMA). Blood samples were taken on the 1st, 10th, and 20th days of menstruation. Apolipoprotein AI and B was determined by means of rocket electroimmunepnoresis using antisera and standards. The relative concentrations of AI-HDL (high density lipoprotein) - and (AI + AII)HDL-subpopulations were also measured. HDL-cholesterol and triglyceride were determined enzymatically. EES effected a continuous increase of Apo AI during 20 cycle days, while the rise of (AI + AII)HDL particles occurred only between the 2nd and 3rd measurements of Apo-AI increase. The estrogen-induced AI-HDL increase was reversed by NG and NOR, while DG and STS halted a further increase holding the value at the level of the 2nd measurement. CMA did not affect the estrogen-induced AI-HDL increase. A noticeable increase of Apo-AI concentration also took place under DG,STS, and CMA between the 2nd and 3rd measurements, as the estrogen-induced (AI + AII)HDL increase is not inhibited by gestagens. NG induced only a slight elevation of Apo B by the 3rd measurement, however, compared to the 2nd time period, Apo B concentration diminished in the first 10 days (it seemed estrogen induced). The change of Apo B concentration is the result of the change of Apo B-containing lipoproteins. Triglycerides increased under the effect of estrogens, and only NG and NOR influenced the estrogen- dependent increase of triglyceride concentration. The strongest correlation was found between AI-HDL and HDL cholesterol as well as Apo AI. In summation, the atherogenic risks of preparations containing EES, CMA, DG are slight because of the high concentration of AI-HDL. In contrast, NOR and NG are not gestagens of choice owing to their strong AI-HDL lowering effect and their effect raising Apo B concentration. Language: German Keywords: COMPARATIVE STUDIES | ORAL CONTRACEPTIVES | CONTROL GROUPS | ETHINYL ESTRADIOL | LEVONORGESTREL | DESOGESTREL | CHLORMADINONE ACETATE | ATHEROSCLEROSIS | MENSTRUAL CYCLE | LABORATORY EXAMINATIONS AND DIAGNOSES | BLOOD PROTEINS | LIPID METABOLIC EFFECTS | ADMINISTRATION AND DOSAGE | Studies | Research Methodology | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contraceptive Agents | Contraceptive Agents, Progestin | Arteriosclerosis | Arterial Occlusive Diseases | Vascular Diseases | Diseases | Menstruation | Reproduction | Examinations and Diagnoses | Hemic System | Physiology | Biology | Lipids | Drugs | Treatment Document Number: 060467 |
| 21. Peer Reviewed Title: Metabolic changes in women using a long-acting monthly oral contraceptive and return of ovulation on discontinuation. Author: Yu AF; Wu SX; Liu JL; Liu AR; Li JZ; Wu JH; Hu ZZ; Yin BY; Xu GX; Fotherby K Source: CONTRACEPTION. 1988 May;37(5):517-28. Abstract: Metabolic changes were investigated in 2 groups of women using OCs for 5-16 years. Blood samples were taken during the last cycle of oral contraceptive (OC) use and 3 months posttreatment. 1 group had used a monthly OC (MOC, 3 mg quinestrol and 10 mg 16-methylene chlormadinone acetate) and the 2nd group a daily OC (DOC, 35 mcg ethinyl estradiol + 0.625 mg norethisterone). During treatment, there were increases in serum total cholesterol and triglycerides but not HDL-C, in plasma total cortisol but not in renin activity, angiotensin II, or urinary free cortisol excretion, in hemoglobin and some coagulation factors but not factor X or antithrombin III, platelet function, or fibrinolysis. The area under the blood glucose concentration-time curve, but not that for serum insulin, was slightly increased, and there was no change in fasting blood sugar concentrations. All metabolic parameters, except plasma cortisol, which had shown an increase on treatment, had decreased to control levels within 3 months. Ovulation returned promptly in all women, the mean time being 70 days for group MOC and 44 days for group DOC. Thus, in spite of the long duration of use of the OCs, metabolic changes were minor. (author's) Language: English Keywords: UNITED KINGDOM | ORAL CONTRACEPTIVES | CHLORMADINONE ACETATE | LABORATORY EXAMINATIONS AND DIAGNOSES | ESTRADIOL | PROGESTERONE ANALYSIS | LIPID METABOLIC EFFECTS | HEMOGLOBIN LEVEL | CARBOHYDRATE METABOLIC EFFECTS | HEMIC SYSTEM | OVULATION | ADMINISTRATION AND DOSAGE | ANALYSIS | CHANGES | Developed Countries | Europe, Western | Europe | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Examinations and Diagnoses | Estrogens | Hormones | Endocrine System | Physiology | Biology | Progesterone | Progestational Hormones | Lipids | Metabolic Effects | Reproduction | Drugs | Treatment | Research Methodology | Social Change Document Number: 050081 |
| 22. Title: [Progestagens as contraceptives] Progestagene zur Empfangnisverhutung. Author: Kuhl H Source: WIENER MEDIZINISCHE WOCHENSCHRIFT. 1987;137(18-19):433-40. Abstract: The different spectrum of biological actions of the various synthetic progestogens is compared on the basis of chemical structure, pharmacokinetics, and interaction with the multiple receptors. The mechanism of action of the progesterone derivatives (medroxyprogesterone acetate, chlormadinone acetate, and cyproterone acetate), the norethisterone-related (norethisterone, ethynodiol diacetate, lynestrenol, and norethynodrel), and the norgestrel-related progestogens (levonorgestrel, desogestrel, gestodene, and norgestimate), and a possible influence of some metabolites on the biological profile are discussed. With regard to progestogenic activity, the time course of the serum concentrations of the steroids after the application (pharmacokinetics) which is dependent on absorption, metabolization in the gastrointestinal tract and liver (1st-pass effect), distribution and storage in fat and other tissues, binding to serum proteins, inactivation, and conjugation is of particular importance. The various side effects of the progestogens are based mainly on their influence on hepatic metabolism (lipids, lipoproteins, serum proteins) and upon other organs which influence their estrogenic, antiestrogenic, androgenic, antiandrogenic, glucocorticoid, and antimineralocorticoid actions. (author's modified) (summaries in ENG, GER) Language: German Keywords: HORMONES | REPRODUCTIVE CONTROL AGENTS | STEROID METABOLIC EFFECTS | METABOLIC EFFECTS | LIPID METABOLIC EFFECTS | SIDE EFFECTS | ANALYSIS | MEDROXYPROGESTERONE ACETATE | CHLORMADINONE ACETATE | CYPROTERONE ACETATE | NORETHINDRONE | LYNESTRENOL | ETHYNODIOL DIACETATE | NORETHYNODREL | LEVONORGESTREL | Endocrine System | Physiology | Biology | Family Planning | Lipids | Treatment | Research Methodology | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Hormone Antagonists Document Number: 051407 |
| 23. Title: [Progestogen contraception using chlormadinone acetate in women presenting high vascular risk. (A gynecoendocrine, metabolic and vascular study)] Contraception progestative par l'acetate de chlormadinone chez des femmes a risque vasculaire: (etude gyneco-endocrinienne, metabolique et vasculaire). Author: Pelissier C; Basdevant A; Conard J; Egloff M; Husson T; Guyenne TT Source: Contraception, Fertilite, Sexualite. 1987 Jan;15(1):45-54. Abstract: 20 women with metabolic, vascular, or gynecoendocrinological contraindications to use of combined oral contraceptives (OCs) or norsteroid progestins participated in a 6-month study of chlormadinone acetate, a progestin derived from 17-OH progesterone known for its weak androgenic activity. 5 mg doses of chlormadinone acetate were administered on the morning and evening of the 6th to the 26th cycle day for 3 woman and on the 8th to the 26th cycle day for 17 others. Blood tests were conducted during the luteal phase after fasting. The average age of the study subjects was 29.9, the average weight was 57.8 kg, and the average height was 161 cm. There were no significant variations over the course of the study in weight, blood pressure, renin substrate, high density lipoprotein (HDL) cholesterol, triglycerides, plasma apo-B, or antithrombin III. There was a significant reduction in apoprotein A1, the principle protein fraction of high density lipoproteins, from the 3rd to the 6th cycles, and a nonsignificant reduction of the apoprotein B. The ratio of A1/B apoproteins was not significantly modified. There were no signs of hyperestrogenism, hyperandrogenic effects, or digestive intolerance. In most cases there was no significant change in cycle duration or intensity of menstrual bleeding. 3 patients were recurrently amenorrheic. The amount of bleeding was considered normal by 14 patients and diminished by 3. There were no cases of menorrhagia and 5 of minor metrorrhagia in the first 3 months of use. No pregnancies occurred. After voluntary termination of contraception, 2 patients rapidly became pregnant. Measurement of ovarian hormone levels and gonadotropins indicated that chlormadinone acetate at the prescribed dose completely inhibited progesterone secretion in all patients and considerably reduced the production of estradiol in the luteal phase. Chlormadinone acetate has the dual advantages of avoiding the estrogen-induced side effects of combined OCs and avoiding hyperestrogenism. The use of a progestin derived from 17-OH progesterone may offer a contraceptive method suitable for women with metabolic or vascular contraindications to combined OCs or gynecoendocrinological contraindications to low dose progestins, who are unable or unwilling to use mechanical or local contraceptives. Chlormadinone acetate should however remain a method for use under exceptional circumstances. Language: English Keywords: FRANCE | EUROPE, WESTERN | EUROPE | CLINICAL RESEARCH | RESEARCH AND DEVELOPMENT | CHLORMADINONE ACETATE | EVALUATION | HORMONES | REPRODUCTIVE CONTROL AGENTS | CONTRACEPTIVE AGENTS, PROGESTIN | CONTRACEPTIVE AGENTS, ESTROGEN | CONTRACEPTIVE AGENTS, FEMALE | CONTRACEPTION | FAMILY PLANNING | CARDIOVASCULAR EFFECTS | METABOLIC EFFECTS | DISEASES | CONTRAINDICATIONS | REVERSIBILITY | Developed Countries | Research Methodology | Technology | Economic Factors | Contraceptive Agents | Endocrine System | Physiology | Biology | Treatment Document Number: 043371 |
| 24. Title: Changes in lipoproteins with various sex steroids. Author: Teran AZ; Greenblatt RB; Chaddha JS Source: OBSTETRICS AND GYNECOLOGY CLINICS OF NORTH AMERICA. 1987 Mar;14(1):107-19. Abstract: In a series of studies investigating the effects of natural and synthetic sex steroids, given by various routes, on lipoproteins in men and women, this review emphasizes subcutaneous pellet administration of natural testosterone and estradiol. It has been reported over the years that oral contraceptives increase cholesterol and triglycerides, and decrease HDL and LDL. Age alone seems to be the determining factor causing coronary heart disease in women, due to low endogenous estrogens. HDL and LDL, a remnant of the VLDL lipoprotein, are implicated atherogenesis. In 191 men treated with pure crystalline testosterone pellets, 75 mg per 10-20 pounds body weight per 6 months, there was a small, but significant increase in HDL, and a decrease in cholesterol: HDL ratio and LDL: HDL ratios at 6 and 12 months. No significant differences were recorded after 2 to 10 years. In 91 women implanted with estradiol pellets for contraception, and given oral progestins from Day 16-25, the effects on lipoproteins depended on the specific progestin used. Norethindrone acetate 5 mg decreased HDL at 6 months, but not at 12 months. Norgestrel 0.0075 mg decreased VLDL at 6 and 12 months, but did not affect HDL or LDL. Medroxyprogesterone acetate, 10 mg did not change lipoproteins significantly. Estradiol pellets alone did not alter lipids in 46 postmenopausal women. Gn-RH or its agonist danazol effectively blocked pituitary function in 17 women with endometriosis, and raised LDL significantly. Language: English Keywords: GEORGIA (UNITED STATES) | UNITED STATES OF AMERICA | CONTRACEPTIVE IMPLANTS | CONTRACEPTIVE AGENTS, PROGESTIN | CONTRACEPTION RESEARCH | FEMALE CONTRACEPTION | HORMONE ANTAGONISTS | HORMONES | CHLORMADINONE ACETATE | NORETHINDRONE ACETATE | NORGESTREL | PITUITARY HORMONE RELEASING HORMONES | ANDROGENS | TESTOSTERONE | ESTRADIOL | LIPID METABOLIC EFFECTS | LIPIDS | CHOLESTEROL | ENDOMETRIAL EFFECTS | MENOPAUSE | CLINICAL RESEARCH | North America | Americas | Developed Countries | Contraceptive Methods | Contraception | Family Planning | Contraceptive Agents, Female | Contraceptive Agents | Endocrine System | Physiology | Biology | Norethindrone | Estrogens | Endometrium | Uterus | Genitalia, Female | Genitalia | Urogenital System | Reproduction | Research Methodology Document Number: 057382 |
| 25. Title: Endocrine effects of systemic, steroidal contraceptives. Author: Edgren RA Source: In: Contraceptive steroids: pharmacology and safety, edited by A.T. Gregoire and Richard P. Blye. New York, New York, Plenum, 1986. :163-78. Abstract: Researchers have been able to predict clinical effects of systemic, steroidal contraceptives based on animal models. They cannot accurately predict, however, what quantities are appropriate for humans. Therefore, scientists should depend on human data to identify the optimum dose. Estrogens bind to cytoplasmic receptors in laboratory animals which cause several effects including prevention of uterine growth, particularly the preovulatory endometrium,; control of cyclic changes in the vagina; and regulation of the menstrual cycle. When estrogens are administered simultaneously with progestagens, however, the estrogenic induced uterine and vaginal effects do not appear. Most progestagens bind to the endometrial progesterone receptor, except those that are derivatives of 19-nortestosterone. Further, some bind to the testosterone receptor and produce androgenic effects. Progestational effects consist of secretory change of the uterus, delay of menstruation, and efficacy as an oral contraceptive when combined with estrogen. The progestogen, medroxyprogesterone acetate, binds to the glucocorticoid receptor. Toxicological tests indicate clinical corticoid action, such as deterioration of the adrenal gland. These effects have not yet appeared in Depo Provera users, however. Recommendations for preclinical criteria include not changing present requirements for endocrine studies and pharmacological and clinical effects, allow field trials after 6 months of toxicity studies in 2 species, narrow toxicity criteria to those established for other classes of drugs, and no longer require the 7 year dog and 10 year monkey studies which test for tumor development. Language: English Keywords: UNITED STATES OF AMERICA | CALIFORNIA | GOVERNMENT AGENCIES | CONTRACEPTIVE AGENTS, PROGESTIN | CHLORMADINONE ACETATE | ETHINYL ESTRADIOL | ETHYNODIOL DIACETATE | LEVONORGESTREL | LYNESTRENOL | DEPO-PROVERA | MESTRANOL | NORETHINDRONE | NORETHINDRONE ACETATE | NORETHYNODREL | NORGESTREL | QUINGESTANOL ACETATE | TESTOSTERONE | PROGESTERONE | ESTRADIOL | ENDOCRINE EFFECTS | LABORATORY ANIMALS | INJECTABLES | ORAL CONTRACEPTIVES, COMBINED | Developed Countries | North America | Americas | Organizations | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Medroxyprogesterone Acetate | Androgens | Hormones | Endocrine System | Physiology | Biology | Progestational Hormones | Estrogens | Clinical Research | Research Methodology | Contraceptive Methods | Oral Contraceptives Document Number: 058689 |
| 26. Title: The role of pharmacokinetics in preclinical safety studies of synthetic sex steroids. Author: Humpel M; Dusterberg B; Beier S; Schuppler J; Gunzel P; Elger W Source: In: Contraceptive steroids: pharmacology and safety, edited by A.T. Gregoire and Richard P. Blye. New York, New York, Plenum, 1986. :47-65. Abstract: Research shows that differences exist between data on the pharmacokinetics of various progestogen. For example, the bioavailability for 5 progestogen, including ethinyl estradiol, was higher in humans than in the animals. Further, researchers administered therapeutic doses to humans while animals received much higher doses. Even in 1 animal species, extreme differences occur in the rate of metabolism of different sex steroids. In addition, 1 progestin is metabolically converted at various rates in different animals. These differences in data lead scientists to debate over what stage of drug development should different sex steroid toxicity data be available. 6 researchers of synthetic sex steroids form West Germany have proposed a compromise. Researchers should obtain pharmacokinetic data on bioavailability in dose dependency, total or metabolic clearance, and terminal half life of the active principle concentration in plasma on that animal species used for 12 week or longer tolerance studies. In those cases where no common animal species meets the bioavailability criterion, various routes of administration must be considered even if the drug is administered orally. Researchers should interpret toxicity of a given sex steroid using active principle bioavailability and directly compare plasma levels in humans and animal species. Further, they advocate the reexamination of former animal tolerance studies to confirm their relevance of estimating the risks in humans. Since research finding suggest no biological foundation for high multiples of human dosage, the scientific community should no longer require them. Language: English Keywords: UNITED STATES OF AMERICA | FEDERAL REPUBLIC OF GERMANY | CONTRACEPTIVE AGENTS, PROGESTIN | CHLORMADINONE ACETATE | ETHINYL ESTRADIOL | LEVONORGESTREL | MEDROXYPROGESTERONE ACETATE | PROGESTERONE | STEROID METABOLIC EFFECTS | PLASMA PROTEIN BINDING CAPACITY | LABORATORY ANIMALS | Developed Countries | North America | Americas | Europe, Central | Europe | Contraceptive Agents, Female | Contraceptive Agents | Contraception | Family Planning | Contraceptive Agents, Estrogen | Progestational Hormones | Hormones | Endocrine System | Physiology | Biology | Metabolic Effects | Hemic System | Clinical Research | Research Methodology Document Number: 058688 |
| 27. Peer Reviewed Title: Progestins and carbohydrate metabolism. Author: Rabe T; Runnebaum B Source: INTERNATIONAL JOURNAL OF FERTILITY. 1986;Suppl:31-45. Abstract: The effect of oral contraceptives (OCs) on carbohydrate metabolism depends on the amount of estrogen (ethinyl estradiol or mestranol), type and amount of progestin, formulation of the pill (monophasic, sequential, or triphasic), duration of use, mode of administration (oral vs. parenteral), and race and genetic predisposition of the user. The progestin megestrol has minimal effect on carbohydrate metabolism but is no longer available due to its carcinogenic effects in beagle dogs. Combination pills with norethindrone and its derivatives (norethindrone acetate, norethynodrel, and ethynodiol diacetate) show moderate impairment of glucose tolerance with definite hyperinsulinemia. The lowest metabolic effect was observed with triphasic formulations. The effect of levonorgestrel depends on the formulation; the highest impairment of glucose and insulin response after oral glucose loading is found in sequential and combined formulations with doses of 50 mcg ethinyl estradiol, whereas with doses of 30 mg ethinyl estradiol only minor effects on glucose tolerance are seen. Therefore, to minimize disturbances of carbohydrate metabolism, low-dose formulations and triphasic preparations should be used. (author's) Language: English Keywords: CARBOHYDRATE METABOLIC EFFECTS | ORAL CONTRACEPTIVES | ESTROGENS | PROGESTERONE | NORETHINDRONE | NORETHINDRONE ACETATE | MEDROXYPROGESTERONE ACETATE | CHLORMADINONE ACETATE | NORGESTREL | GLUCOSE TOLERANCE TEST | LEVONORGESTREL | SIDE EFFECTS | CONTRACEPTIVE AGENTS, SIDE EFFECTS | WOMEN | Metabolic Effects | Physiology | Biology | Contraceptive Methods | Contraception | Family Planning | Hormones | Endocrine System | Progestational Hormones | Contraceptive Agents, Progestin | Contraceptive Agents, Female | Contraceptive Agents | Laboratory Procedures | Laboratory Examinations and Diagnoses | Examinations and Diagnoses | Treatment | Demographic Factors | Population Document Number: 058640 |
| 28. Title: [Hormones and lupus] Hormones et lupus. Author: Gompel A; Pelissier C; Kuttenn F; Mauvais-Jarvis P Source: REVUE DE MEDECINE INTERNE. 1985 Dec;6(5):543-52. Abstract: Although the etiology of lupus is imperfectly understood, immune factors, heredity, viral infections, and hormonal status are known to play a role. Studies of the sex ratio of lupus patients indicate that before age 10, twice as many girls as boys are affected, but after 12 years, 9.6 females are affected for each male. The incidence of lupus is almost constant for males of all ages but is much higher for women of fertile age than for other women. The deleterious effect of synthetic estrogens was 1st reported in 1966, and various studies since then have confirmed the results. The etiologic role of pregnancy is debated, but pregnancies can be successfully carried to term in periods of remission. Certain lines of mice spontaneously develop an autoimmune disease resembling disseminated lupus erythematosus. Anti-DNA antibodies appear earlier in the female and death from renal insufficiency occurs earlier than in males. Prepubertal castration does not influence the survival of female mice but significantly reduces that of males. Treatment with estradiol diminishes survival of castrated males and females, while treatment with androgens increases survival time of castrated to control females and of castrated males to that of control males. The timing and dose of treatment modify the response. Progesterone administered alone does not influence survival time of females but somewhat increases that of castrated males. Cyproterone acetate, an antiandrogenous progestin, has no effect in 2-3 week old males. Danazol, a moderately active androgen, has no effect on female mice. Nafoxidine, an antiestrogen, increases survival times. These results support the opinion that estrogens aggravate lupus while androgens have a protective effect. Different hormonal treatments have been prescribed for human lupus. Some beneficial effect for female patients has been observed with danazol, but the drug entails significant hepatic, metabolic, and hypertensive risks and may produce androgenic side effects such as voice modifications and hirsutism. Cyproterone acetate, a derivative of 17-hydroxyprogesterone, is without vascular and metabolic side effects and can halt ovarian function at a dose of 50 mg/day. It behaves as a peripheral antiandrogen and may have androgen agonist activity in some tissues. The mechanism of interaction of sex hormones in lupus may be explained by their influence on cellular and humoral immunity. Estrogens appear to suppress cellular immunity and stimulate humoral immunity, while androgens appear to play a suppressive role at the 2 levels. Contraception for women with lupus must be effective. Combined oral contraceptives and low-dose norsteroid progestins are contraindicated because of their thromboembolic and vascular risks. Low-dose progestins may be used but cause hyperestrogenism in some women. Chlormadinone acetate at a daily dose of 10 mg has no significant vascular effect. IUDs may have reduced efficacy during corticotherapy and pose a risk of infection. Only mechanical vaginal methods ose no threats for lupus patients, but they must be understood and accepted by the patient. Language: French Keywords: SYSTEMIC LUPUS ERYTHEMATOSUS | DERMATOLOGICAL EFFECTS | DISEASES | ANDROGENS | ESTROGENS | PROGESTERONE | CORPUS LUTEUM HORMONES | HORMONES | REPRODUCTIVE CONTROL AGENTS | LABORATORY ANIMALS | CLINICAL RESEARCH | IN VITRO | RESEARCH AND DEVELOPMENT | IMMUNOLOGIC FACTORS | TREATMENT | ORAL CONTRACEPTIVES, CONTRAINDICATIONS | LOW-DOSE PROGESTINS | CONTRACEPTIVE AGENTS, FEMALE | BARRIER METHODS | CONTRACEPTION | FAMILY PLANNING | CONTRAINDICATIONS | SEX FACTORS | AGE FACTORS | IMMUNITY, CELLULAR | CHLORMADINONE ACETATE | IUD | Physiology | Biology | Endocrine System | Progestational Hormones | Research Methodology | Technology | Economic Factors | Immunity | Immune System | Contraceptive Safety | Safety | Public Health | Health | Contraceptive Agents, Progestin | Contraceptive Agents | Contraceptive Methods | Population Characteristics | Demographic Factors | Population Document Number: 039934 |
| 29. Title: Oral contraceptives and breast cancer: laboratory evidence. Author: Shubik P Source: Iarc Scientific Publications. 1985;(65):33-5. Abstract: This article reviews laboratory evidence on the association between oral contraceptive (OC) use and breast cancer. Since there are about 100 OC formulations available, which have minor but significant variations in their chemical structure, a few key representative compounds are selected as the focus for this discussion. When tested alone, mestranol increased the incidence of pituitary and mammary tumors in mice, seemed to be inactive in rats, and increased the incidence of mammary tumors in dogs. When it was tested along with norethynodrel, mice also developed squamous cell tumors of the vagina and cervix and rats developed mammary tumors and benign liver tumors. When tested alone norethisterone enhanced the incidence of pituitary and benign liver adenomas as well as granulosa cell tumors of the ovary in mice. When tested in combined form with ethinyl estradiol, mammary tumor incidence was enhanced in both mice and rats, liver tumors were noted, and pituitary tumor incidence was enhanced in mice. Medroxyprogesterone acetate enhanced mammary tumor incidence in dogs and had no effect in mice. Testing of chlormadinone acetate produced negative results in mice and rats, but mammary tumors were reported in dogs. When the compound was tested in combination with mestranol, controversial evidence of enhancement of mammary tumor incidence was obtained in mice. The significance of these findings is unclear. The mammary tumors seen in beagle dogs, for example, are mixed-cell tumors that bear little similarity to their human counterparts. Overall, these findings can be summarized as follows: all the OCs and their component compunds are carcinogenic in rodents or dogs, while the presently available data on monkeys are incomplete but seemingly negative. Toxicologists now face the challenge of validating their approach to extrapolation of these results to humans. Language: English Keywords: ORAL CONTRACEPTIVES, SIDE EFFECTS | BREAST CANCER | MESTRANOL | HORMONES | NORETHYNODREL | NORETHINDRONE | MEDROXYPROGESTERONE ACETATE | CHLORMADINONE ACETATE | LABORATORY ANIMALS | CONTRACEPTIVE METHODS | SIDE EFFECTS | Contraceptive Safety | Safety | Public Health | Health | Cancer | Neoplasms | Diseases | Contraceptive Agents, Estrogen | Contraceptive Agents, Female | Contrace |