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1.
Eur J Epidemiol ; 36(8): 827-839, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33331993

ABSTRACT

Oral contraceptives (OCs) have been associated with long-term lower endometrial cancer risk; relatively little is known about associations with more recent OC formulations and associations with longer-term risk. A total of 107,069 women from the Nurses' Health Study II recalled OC use from age 13 to baseline (1989); biennial questionnaires updated data on OC use until 2009. OCs were classified by estrogen and progestin type, dose, and potency based on reported brand. 864 incident endometrial cancer cases were identified through 2017. Multivariable Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals [95% CI] for the association of OC use with endometrial cancer risk. OC use was associated with lower endometrial cancer risk (ever use, HR 0.77 [95% CI 0.65-0.91]; >10 years of use, 0.43 [0.32-0.58] vs. never OC use). Inverse associations for duration were evident regardless of time since last use. Longer durations (> 5 years) of ethinyl estradiol (0.52 [0.41-0.67]) and second-generation progestins (0.43 [0.30-0.61]), both versus never use, were more strongly associated with lower risk than mestranol (0.66 [0.50-0.88], p-het = 0.01) and first-generation progestins (0.62 [0.49-0.78], p-het = 0.03). Inverse associations were generally observed for cross-classified cumulative average estrogen and progestin dose and potency (< vs. ≥ median; ever use vs. never OC use), with the exception of high estrogen and low progestin dose. OCs were associated with lower endometrial cancer risk, independent of time since last use. Use of ethinyl estradiol and second-generation progestins were more strongly inversely associated with risk compared with older formulations.


Subject(s)
Contraceptives, Oral, Hormonal/adverse effects , Endometrial Neoplasms/chemically induced , Adult , Aged , Cohort Studies , Contraceptives, Oral, Hormonal/administration & dosage , Endometrial Neoplasms/epidemiology , Estrogens/administration & dosage , Estrogens/adverse effects , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/adverse effects , Female , Humans , Mestranol/administration & dosage , Mestranol/adverse effects , Middle Aged , Progestins/administration & dosage , Progestins/adverse effects , Prospective Studies
2.
J Clin Pharmacol ; 49(7): 807-15, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19443681

ABSTRACT

The pharmacokinetics of oral contraceptive (OC) components, ethinyl estradiol (EE) and norethindrone (NET), were evaluated after coadministration with etoricoxib in 3 double-blind, randomized, 2-period crossover studies of healthy women. There were 16, 39, and 24 participants enrolled in studies 1 (part I, part II), and 2, respectively. Each participant received triphasic OC (EE 35 microg/NET 0.5 mgx7 days, 0.75 mgx7 days, 1.0 mgx7 days) throughout each 28-day period. OC was coadministered with 21 days of etoricoxib daily followed by placebo for 7 days; the alternate period followed the reverse regimen (placebo to etoricoxib). Study 1 (part I) examined concurrent (morning) administration of OC/etoricoxib 120 mg, study 1 (part II) examined staggered (morning/night) administration of OC/etoricoxib 120 mg, and study 2 examined concurrent (morning) administration of OC/etoricoxib 60 mg. Coadministration of OC and etoricoxib 120 mg once daily was associated with a approximately 50% to 60% increase in EE concentrations, whereas etoricoxib 60 mg once daily was associated with a approximately 37% increase in EE concentrations. Coadministration of OC and etoricoxib was generally well tolerated. A clinically important change in NET AUC0-24 h was not observed. Adverse events included dyspepsia, diarrhea, headache, nausea, fatigue, loss of appetite, and taste disturbance.


Subject(s)
Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Combined/pharmacokinetics , Cyclooxygenase Inhibitors/administration & dosage , Mestranol/administration & dosage , Mestranol/pharmacokinetics , Norethindrone/administration & dosage , Norethindrone/pharmacokinetics , Pyridines/administration & dosage , Pyridines/pharmacology , Sulfones/administration & dosage , Sulfones/pharmacology , Adolescent , Adult , Contraceptives, Oral, Combined/adverse effects , Cyclooxygenase Inhibitors/adverse effects , Cyclooxygenase Inhibitors/pharmacology , Drug Combinations , Drug Interactions , Etoricoxib , Female , Headache/chemically induced , Humans , Mestranol/adverse effects , Middle Aged , Nausea/chemically induced , Norethindrone/adverse effects , Pyridines/adverse effects , Serum Albumin/metabolism , Sex Hormone-Binding Globulin/metabolism , Sulfones/adverse effects
4.
Contraception ; 68(3): 159-76, 2003 Sep.
Article in English | MEDLINE | ID: mdl-14561536

ABSTRACT

A randomized controlled multicenter study was undertaken to monitor the effects on hemostasis of two once-a-month injectable contraceptive preparations, Mesigyna (50 mg norethisterone enanthate and 5 mg estradiol valerate) and Cyclofem (25 mg medroxyprogesterone acetate and 5 mg estradiol cypionate) in comparison with a well-known oral contraceptive (OC) Ortho-Novum 1/35 (norethisterone 1 mg and ethinyl estradiol 35 microg). A total of 378 volunteers from four centers (Bangkok, Hangzhou, Santiago and Singapore) were monitored. Blood sampling took place in one pretreatment cycle, the third and ninth injection intervals and one posttreatment cycle. In each of the three treatment groups, a rise in hemoglobin, and increases in platelet count and in prothrombin time were observed. With treatment there was a significant increase in activated partial thromboplastin time among Mesigyna users, no change among Cyclofem users and a significant decrease among OC users. OC use led to increases in plasma levels of fibrinogen, factor VII, factor X, plasminogen, protein C and decreases in plasma levels of t-PAI and antithrombin. Use of combined injectables induced no change (Cyclofem) or decreases (Mesigyna) in plasma levels of fibrinogen, factor VII, factor X and antithrombin. Use of both combined injectables led to decreases in protein C, slight decreases in plasminogen and increases in plasminogen and fibrinogen. Overall, the injectable preparations may be more beneficial than the oral preparation in not enhancing a hypercoagulable state because of the reduced synthesis of fibrinogen, factors VII and X; however, decreases in antithrombin and protein C, which are potent coagulation inhibitors, may raise some concern. Whether these changes can lead to modifications in the risk of arterial or venous disease can only be ascertained by conducting epidemiological studies.


Subject(s)
Blood Coagulation/drug effects , Contraceptive Agents, Female/adverse effects , Contraceptives, Oral, Combined/adverse effects , Estradiol/analogs & derivatives , Estradiol/adverse effects , Fibrinolysis/drug effects , Medroxyprogesterone Acetate/adverse effects , Mestranol/adverse effects , Norethindrone/analogs & derivatives , Norethindrone/adverse effects , Adolescent , Adult , Antithrombins/analysis , Cardiovascular Diseases/chemically induced , Contraceptive Agents, Female/administration & dosage , Contraceptives, Oral, Combined/administration & dosage , Drug Combinations , Estradiol/administration & dosage , Factor VII/analysis , Factor X/analysis , Female , Fibrinogen/analysis , Hemoglobins/analysis , Humans , Injections , Medroxyprogesterone Acetate/administration & dosage , Mestranol/administration & dosage , Norethindrone/administration & dosage , Partial Thromboplastin Time , Plasminogen/analysis , Plasminogen Inactivators/blood , Platelet Count , Protein C/analysis , Prothrombin/analysis
5.
Spine (Phila Pa 1976) ; 27(16): E377-81, 2002 Aug 15.
Article in English | MEDLINE | ID: mdl-12195080

ABSTRACT

STUDY DESIGN: A case report is presented. OBJECTIVES: To present a very rare case of orally ingested sex hormone pills inducing nondurally attached meningioma in the lumbosacral region. SUMMARY OF BACKGROUND DATA: Meningiomas are known to enlarge in response to female sex hormones. At this writing, few cases of nondurally based intradural meningioma have been reported. Moreover, meningiomas in the lumbosacral region are very rare. Spinal meningiomas predominantly arise in the fourth to sixth decades of life and are more common in women. METHODS: The patient was a 20-year-old woman. She had undergone oral sex steroid therapy for long-term oligomenorrhea. The patient complained of intolerable lumbago and numbness in her buttocks. Nonopioid analgesics did not relieve her pain, and she was unable to walk without the aid of a walker. Radiography disclosed a lumbosacral intradural tumor. RESULTS: Complete removal of the tumor was performed. The tumor was not adherent to the dura, and its appearance was that of a typical neurilemmoma. However, the pathologic diagnosis was meningioma. CONCLUSIONS: The tumor in the reported case may have enlarged in response to orally ingested sex steroid pills. Nondural attachment intradural meningiomas are quite uncommon. The gross appearance of the tumor during surgery was typical of neurilemmoma. All the cases reported so far, including the current case, have involved tumor located in the lumbosacral region. Care must be taken in the management of lumbosacral intradural tumors because tumors resembling neurilemmoma may in fact represent meningioma, some subtypes of which possess a high rate of recurrence.


Subject(s)
Dura Mater/pathology , Gonadal Steroid Hormones/adverse effects , Meningioma/chemically induced , Meningioma/diagnosis , Spinal Cord Neoplasms/chemically induced , Spinal Cord Neoplasms/diagnosis , Administration, Oral , Adult , Cauda Equina/diagnostic imaging , Cauda Equina/pathology , Cauda Equina/surgery , Chlormadinone Acetate/administration & dosage , Chlormadinone Acetate/adverse effects , Diagnosis, Differential , Dura Mater/surgery , Female , Gonadal Steroid Hormones/administration & dosage , Humans , Hypesthesia/etiology , Low Back Pain/etiology , Lumbosacral Region , Magnetic Resonance Imaging , Meningioma/surgery , Mestranol/administration & dosage , Mestranol/adverse effects , Myelography , Neurilemmoma/diagnosis , Oligomenorrhea/drug therapy , Spinal Cord Neoplasms/surgery , Spine/diagnostic imaging , Spine/pathology , Spine/surgery , Treatment Outcome
7.
Contraception ; 61(5): 295-302, 2000 May.
Article in English | MEDLINE | ID: mdl-10906499

ABSTRACT

The contraceptive efficacy, cycle control, and safety of a new low-dose, triphasic desogestrel/ethinyl estradiol oral contraceptive (CTR 77, Cyclessa(TM)) was compared to that of a marketed, triphasic norethindrone/ethinyl estradiol oral contraceptive (Ortho-Novum(R) 7/7/7). Two identical multicenter, open-label, randomized, parallel group, comparative Phase III 6-cycle trials were designed to each enroll 4200 healthy women. The combined comparative data for Cyclessa versus Ortho-Novum 7/7/7 for both studies are reported here. Cyclessa and Ortho-Novum 7/7/7 had comparable contraceptive efficacy. Despite a lower ethinyl estradiol dose (25 microg/day vs. 35 microg/day), the Cyclessa group had significantly improved cycle control in comparison to the Ortho-Novum 7/7/7 group for presence of a withdrawal bleed (p = 0.001), lack of early withdrawal bleed (p = 0.01), and breakthrough bleeding/spotting (p = 0.001). For each of the months of the study, the incidence of breakthrough bleeding/spotting was lower in the Cyclessa group than the Ortho-Novum 7/7/7 group (breakthrough bleeding, p = 0.006; breakthrough spotting, p = 0.001). The incidence of other adverse events was similar among treatment groups, an observation that supports the safety of both formulations. There was significantly less weight gain (p = 0.0002) and less increase in the body mass index (BMI) (p = 0.0002) in the Cyclessa group. The contraceptive efficacy and safety of Cyclessa is comparable to Ortho-Novum 7/7/7. Cyclessa provides significantly improved cycle control with no weight gain.


Subject(s)
Contraceptives, Oral, Combined , Desogestrel , Ethinyl Estradiol , Menstrual Cycle , Mestranol , Norethindrone , Adolescent , Adult , Body Mass Index , Contraceptives, Oral, Combined/adverse effects , Desogestrel/adverse effects , Drug Combinations , Ethinyl Estradiol/adverse effects , Female , Humans , Mestranol/adverse effects , Middle Aged , Norethindrone/adverse effects , Pregnancy , Treatment Failure , Uterine Hemorrhage/chemically induced , Weight Gain
8.
Contraception ; 61(1): 51-9, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10745070

ABSTRACT

As part of a 60-week, open-label, nonrandomized, parallel, controlled study comparing a monthly contraceptive injection containing medroxyprogesterone acetate (MPA) 25 mg and estradiol cypionate (E(2)C) 5 mg (Lunelle Monthly Contraceptive Injection) and a norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE) triphasic oral contraceptive (Ortho-Novum(R) 7/7/7), a longitudinal examination of lipid profiles was conducted. Lipid parameters were assessed at screening and at weeks 20, 40, and 60 (or the final visit) in 114 women using MPA/E(2)C and 93 using NET/EE (lipid analysis population). Extra blood samples were obtained at weeks 21, 22, and 23 in 61 MPA/E(2)C users and 51 NET/EE users (index-cycle analysis population) to investigate lipid changes during one cycle of use. In the index-cycle population, median changes from screening to week 60 showed a decrease in apolipoprotein (apo) A-I and apo A-II in both groups. MPA/E(2)C users had a decrease in total cholesterol (C), total triglycerides, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with maintenance of the total C/HDL-C ratio. NET/EE users showed an increase in total C and LDL-C, with no change in HDL-C or the total C/HDL-C ratio. Within the index cycle (weeks 20 to 23), median changes in lipid values in both MPA/E(2)C and NET/EE users were generally greatest during the first week after the injection or the start of the pill pack. The results of this first longitudinal examination of serum lipids in US women using MPA/E(2)C confirm earlier findings in women in other countries. However, a direct comparison of the effects of MPA/E(2)C and NET/EE on lipid profiles was not possible in this study because of its design and because of the baseline and pharmacokinetic/pharmacodynamic differences between the two contraceptive groups. The results of this analysis showed that, although overall lipid values decreased, including a significant decrease in HDL cholesterol, the maintenance of the total-C/HDL-C ratio suggests that the effect of MPA/E(2)C on lipid parameters may not negatively affect CVD risk over 1 year of use. However, these results warrant further investigation, given the nature of this trial.


Subject(s)
Contraceptive Agents, Female/adverse effects , Contraceptives, Oral, Combined/adverse effects , Estradiol/analogs & derivatives , Lipids/blood , Medroxyprogesterone Acetate/adverse effects , Mestranol/adverse effects , Norethindrone/adverse effects , Apolipoprotein A-I/analysis , Apolipoprotein A-II/blood , Apolipoproteins B/blood , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Contraceptive Agents, Female/administration & dosage , Contraceptives, Oral, Combined/administration & dosage , Drug Combinations , Estradiol/administration & dosage , Estradiol/adverse effects , Female , Humans , Medroxyprogesterone Acetate/administration & dosage , Mestranol/administration & dosage , Norethindrone/administration & dosage , Triglycerides/blood
9.
Contraception ; 62(6): 289-95, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11239615

ABSTRACT

Persistent and/or unpredictable bleeding is a common reason for discontinuation of hormonal contraceptive methods. An open-label, nonrandomized, parallel, controlled study compared the efficacy, safety, and cycle control of the new, highly efficacious monthly injectable contraceptive containing 25 mg medroxyprogesterone acetate (MPA) and 5 mg estradiol cypionate (E(2)C) (MPA/E(2)C) (Lunelle Monthly Contraceptive Injection) with that of the frequently used norethindrone 0.5, 0.75, 1.0 mg/0.035 mg ethinyl estradiol (NET/EE) triphasic oral contraceptive (Ortho-Novum 7/7/7). This report directly compares the bleeding patterns of women on MPA/E(2)C to those of women on NET/EE and untreated women. Overall, breakthrough bleeding occurred less frequently in women using MPA/E(2)C than in women using NET/EE (p < or =0.01). However, more women using MPA/E(2)C experienced amenorrhea/missed periods than those on NET/EE (p < or =0.01). In addition, the percentage of women experiencing breakthrough bleeding or amenorrhea while using other oral contraceptives is compared to that of women using MPA/E(2)C. A rapidly reversible method, MPA/E(2)C, combines the high contraceptive efficacy of surgical sterilization with the convenience of monthly administration. These data suggest that, for a large proportion of women, MPA/E(2)C offers predictability in bleeding patterns comparable to or greater than that experienced by ovulatory untreated women or those using combination oral contraceptives.


Subject(s)
Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Hormonal/administration & dosage , Estradiol/analogs & derivatives , Estradiol/administration & dosage , Medroxyprogesterone Acetate/administration & dosage , Mestranol/administration & dosage , Norethindrone/administration & dosage , Uterine Hemorrhage/chemically induced , Adolescent , Adult , Amenorrhea/chemically induced , Body Weight/physiology , Contraceptives, Oral, Combined/adverse effects , Contraceptives, Oral, Hormonal/adverse effects , Drug Combinations , Estradiol/adverse effects , Female , Humans , Medroxyprogesterone Acetate/adverse effects , Mestranol/adverse effects , Middle Aged , Norethindrone/adverse effects , Patient Compliance
10.
Am J Gastroenterol ; 93(8): 1250-4, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9707046

ABSTRACT

OBJECTIVE: The aim of this study was to evaluate the effectiveness and safety of combined hormonal therapy in patients with recurring occult gastrointestinal bleeding of obscure origin. METHODS: This was a prospective longitudinal observational study. The setting was an outpatient private practice affiliated with a large university-based hospital. A total of 43 patients, comprising 14 men and 29 women with a mean age of 74 yr (range 48-86 yr), were included. They had a history of recurrent gastrointestinal bleeding of unknown origin for a period of > 1 yr and had required multiple hospitalizations and transfusions. Patients were initially treated with one Enovid 5-mg tablet containing 5 mg norethynodrel and 75 microg of mestranol. Enovid became commercially unavailable and treatment was changed to Ortho-Novum 1/50, containing 1 mg norethindrone and 0.05 milligrams of mestranol, given one tablet b.i.d. Patients were treated and followed for a mean time of 535 days (range 25-1551 days). All patients acted as their own controls and were followed for compliant behavior with periodic hematocrit, serial stool hemoccults, medication counts, and clinical histories regarding transfusion requirements or hospitalization for bleeding or anemia. RESULTS: Of 43 patients who initially entered the study, 38 were treated with combination hormonal therapy. The remaining five patients were treated with estrogen alone. In 25 patients, initial enteroscopy revealed AVMs in the stomach or proximal small bowel and these were cauterized. In the remaining 18 patients no source of bleeding was found. None of the 38 patients who were treated with combination hormonal therapy rebled as long as they continued their prescribed dosage. All five of the patients treated with estrogen alone had rebleeding episodes. There was no statistical difference with respect to AVM cauterization in the rebleeding rate between those patients who underwent cauterization of their AVMs and those who did not. Side effects of combination hormonal therapy occurred in 11 patients and all were considered to be mild. Seven of these 11 patients (64%) elected to continue treatment. CONCLUSION: In this long-term observational study, combination hormonal therapy was shown to stop rebleeding in patients with occult gastrointestinal bleeding of obscure origin.


Subject(s)
Gastrointestinal Hemorrhage/therapy , Aged , Aged, 80 and over , Chronic Disease , Combined Modality Therapy , Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Combined/adverse effects , Drug Combinations , Drug Evaluation , Electrocoagulation , Endoscopy, Gastrointestinal , Estradiol Congeners/administration & dosage , Estradiol Congeners/adverse effects , Female , Gastrointestinal Agents/administration & dosage , Gastrointestinal Agents/adverse effects , Gastrointestinal Hemorrhage/etiology , Humans , Male , Mestranol/administration & dosage , Mestranol/adverse effects , Middle Aged , Norethindrone/administration & dosage , Norethindrone/adverse effects , Norethynodrel/administration & dosage , Norethynodrel/adverse effects , Occult Blood , Prospective Studies , Recurrence
11.
J Am Acad Dermatol ; 31(2 Pt 2): 390-2, 1994 Aug.
Article in English | MEDLINE | ID: mdl-7913477

ABSTRACT

We describe the worsening of porphyria cutanea tarda in a young woman while she was taking oral contraceptives. However, she did not have an exacerbation during two pregnancies. We conclude that estrogens produced during pregnancy do not exert the same effect as orally administered medications that contain estrogen. The pronounced effect of oral ethinyl estradiol on the liver may be attributed to its first-pass effect on that organ.


Subject(s)
Contraceptives, Oral, Synthetic/adverse effects , Mestranol/adverse effects , Norethindrone/adverse effects , Porphyria Cutanea Tarda/chemically induced , Porphyria Cutanea Tarda/metabolism , Pregnancy Complications/metabolism , Adult , Contraceptives, Oral, Combined/adverse effects , Contraceptives, Oral, Combined/metabolism , Contraceptives, Oral, Synthetic/metabolism , Drug Combinations , Estrogens/biosynthesis , Estrogens/metabolism , Female , Humans , Infant, Newborn , Male , Mestranol/metabolism , Norethindrone/metabolism , Pregnancy
12.
Prev Med ; 22(2): 178-86, 1993 Mar.
Article in English | MEDLINE | ID: mdl-8483857

ABSTRACT

BACKGROUND: Case-control studies of oral contraceptive use and breast cancer have used neighborhood, population, or hospital controls. METHODS: To determine whether this association differs according to type of controls, interview data from 131 incident cases of breast cancer were compared with those of 189 hospital controls and 182 neighborhood controls Study subjects were white females recruited between 1973 and 1975 from among residents of Baltimore City and County ages 18 to 59 years. RESULTS: Adjusted relative odds of breast cancer related to ever versus never use of oral contraceptives were 1.0 and 0.8, using hospital and neighborhood controls, respectively. Relative odds did not increase proportionally to duration of oral contraceptive use or to progestogen potency. Although few subjects had used oral contraceptives for more than 2 years, almost all pill brands contained more than 49 micrograms of ethinyl estradiol or of mestranol. CONCLUSIONS: Results from the present study do not support the hypothesis that early preparations of oral contraceptives increased breast cancer risk among white women, regardless of whether controls are neighbors of the cases or hospital patients. However, its conclusions cannot be generalized to women who began taking the pill before their first full-term birth or took it for more than 2 years.


Subject(s)
Breast Neoplasms/chemically induced , Breast Neoplasms/epidemiology , Contraceptives, Oral/adverse effects , Adolescent , Adult , Age Factors , Case-Control Studies , Dose-Response Relationship, Drug , Educational Status , Ethinyl Estradiol/adverse effects , Female , Humans , Maryland/epidemiology , Matched-Pair Analysis , Mestranol/adverse effects , Middle Aged , Odds Ratio , Research Design , Time Factors
13.
Nihon Kyobu Shikkan Gakkai Zasshi ; 31(1): 99-102, 1993 Jan.
Article in Japanese | MEDLINE | ID: mdl-8468829

ABSTRACT

We present a 53-year-old female with pulmonary embolism (PE), who had been taking oral contraceptive for 13 years. She was admitted to our hospital with upper abdominal pain and was found to be in shock. The diagnosis of PE was made from chest X-ray examination, electrocardiogram and pulmonary angiography. Pulmonary hypertension was observed on right heart catheterization, and an anticoagulant was administered. Multiple defects of the right pulmonary artery were detected on lung perfusion scan, and there were no significant findings on leg phlebogram. Home oxygen therapy was effective for the treatment of pulmonary hypertension and chronic hypoxemia which still persisted after her recovery from the acute stage. We are concerned that wide spread use of oral contraceptives will increase the incidence of PE in the near future in this country. We conclude that contraceptive users should be warned of their higher risk of PE, and that they should visit a clinic for examination.


Subject(s)
Mestranol/adverse effects , Norethindrone/adverse effects , Pulmonary Embolism/chemically induced , Female , Humans , Middle Aged
14.
Orv Hetil ; 134(2): 75-7, 1993 Jan 10.
Article in Hungarian | MEDLINE | ID: mdl-8419886

ABSTRACT

Authors report about a case of total lack of middle phalanxes on the 3d and 4th fingers and a hypoplasia of the surrounding phalanges on the left hand. This is the first report on this type of intercalary type in congenital limb deficiency group. They call attention to one of the so far not sufficiently emphasized hazard of previous periconceptional oral contraceptive use. If there is not enough time left for the total regeneration after the discontinuation of contraceptives, such kind of malformation may develop in the fetus due to the insufficiency of fetal-placental circulation.


Subject(s)
Contraceptives, Oral, Synthetic/adverse effects , Ethynodiol Diacetate/adverse effects , Fingers/abnormalities , Hand Deformities, Congenital/chemically induced , Mestranol/adverse effects , Abnormalities, Drug-Induced , Contraceptives, Oral, Combined/adverse effects , Female , Genetic Counseling , Humans , Infant, Newborn , Pregnancy , Prenatal Exposure Delayed Effects
15.
J Clin Psychiatry ; 53(5): 163-5, 1992 May.
Article in English | MEDLINE | ID: mdl-1592843

ABSTRACT

BACKGROUND: There are no published reports of an association between triphasic oral contraceptives and the development of panic disorder. METHOD: The authors describe two cases in which the use of triphasic oral contraceptives in women appear to have precipitated panic disorder. Treatment with the triphasic oral contraceptives was stopped and the patients were followed for 2 years. RESULTS: Both subjects had rapid and total resolution of their panic disorder symptoms following cessation of triphasic oral contraceptive medications. CONCLUSION: Triphasic oral contraceptives in some predisposed women may lead to precipitation of panic disorder.


PIP: Panic disorder, a severe anxiety disorder, affects 1-2% of the general population, mostly women 20-40 years old. A 29-year-old married white women with no children presented with an 18-month history of panic attacks. Episodes of abrupt anxiety lasted 5-20 minutes and occurred 3-4 times per week accompanied by rapid heart rate, shortness of breath, dizziness, and a fear of losing control. She was evaluated by a cardiologist several months earlier for episodic tachycardia, but the tests were normal. She was taking .5 mg of lorazepam po 2-3 times per month, which relieved her anxiety. Her only other medication was 1 tablet/day of Triphasal oral contraceptive (OC). She was started on treatment with desipramine 10 mg, and the dose gradually increased to 60 mg/day which she was unable to tolerate because of marked anorexia; lorazepam .5 mg bid and 10.5-mg tablet p.r.n. was continued to address excess activation secondary to the tricyclic depressant. She had changed from a constant dose OC (Lo/Ovral) to a triphasic preparation (Triphasil) 6 months prior to the onset of her panic attacks. The OC was halted, and she has experienced no subsequent panic attacks or avoidance behaviors during 2 years of follow-up. In the 2nd case a 39-year-old married white woman with 3 children presented with a 3-year history of panic attacks. She was given Ortho-Novum 7/7/7 1 tablet/day for about 8 months prior to her 1st panic attack, which occurred while she was driving. Her medications were clorazepate 3.75 mg b.i. d. and Ortho-Novum 7/7/7 1 tablet g.d. for 21 days of each month; she had been taking both since October 1984. Her father and brother had exhibited some driving avoidance behaviors. Because the triphasic OC preparation possible precipitated her panic disorder with agoraphobia, she was changed to Ortho-Novum 1/35 OC which has markedly improved her anxiety for 2 years now.


Subject(s)
Contraceptives, Oral, Synthetic/adverse effects , Panic Disorder/chemically induced , Adult , Contraceptives, Oral, Combined/adverse effects , Drug Combinations , Ethinyl Estradiol/adverse effects , Ethinyl Estradiol-Norgestrel Combination , Female , Humans , Mestranol/adverse effects , Norethindrone/adverse effects , Norgestrel/adverse effects , Panic Disorder/psychology
16.
J Intern Med ; 231(5): 561-5, 1992 May.
Article in English | MEDLINE | ID: mdl-1602295

ABSTRACT

The case of a patient with intrahepatic cholestasis, probably induced by an oral contraceptive agent, is reported. Initially, early primary biliary cirrhosis was suspected, but this diagnosis could not be verified either clinically or by immunological tests. Re-examination and re-evaluation of the liver biopsy revealed some eosinophilia and sinusoidal dilatation, changes indicative of drug-induced liver injury. The cholestasis gradually disappeared as indicated both biochemically and histologically, but the elevation of serum alkaline phosphatase levels persisted for some 10 years after termination of drug therapy. Oral contraceptive agent-induced jaundice or cholestasis is generally reported to disappear when the drug is stopped, and we are unaware of similar cases in the literature with a protracted course such as that described here. Still, the circumstances of this patient suggest that a correlation between the oral contraceptive agent and the hepatic reaction is most likely, and we consider it important that colleagues pay attention to this possibility.


Subject(s)
Cholestasis, Intrahepatic/chemically induced , Contraceptives, Oral, Combined/adverse effects , Lynestrenol/adverse effects , Mestranol/adverse effects , Adult , Cholestasis, Intrahepatic/diagnosis , Cholestasis, Intrahepatic/pathology , Clinical Enzyme Tests , Drug Combinations , Female , Humans , Liver/pathology , Liver Function Tests , Time Factors
17.
Contraception ; 44(5): 489-503, 1991 Nov.
Article in English | MEDLINE | ID: mdl-1797464

ABSTRACT

A comparative multicenter clinical trial of two combined oral contraceptives (OCs) differing only in the estrogen content (35 mcg ethinyl estradiol versus 50 mcg mestranol) was conducted at five clinics located in Yugoslavia, Egypt, Sri Lanka, Costa Rica and Mexico. The trial was designed to determine the differences between Norinyl 1+35 (Syntex) and Norinyl 1+50 (Syntex) in rates and reasons of discontinuation, and frequency of selected side effects which might contribute to method discontinuation. This report includes analysis of 1698 women, all of whom were interval patients (at least 42 days but within 26 weeks postpartum), randomly allocated to one of the above OCs between October 1982 and January 1984. Follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. Significantly more women in the Norinyl 1+35 group (p less than .001) reported intermenstrual bleeding (primarily staining and spotting), as well as an increase in the occurrence of intermenstrual bleeding compared to women in the Norinyl 1+50 group. There were no significant differences between the groups for side effects with the exception of more women in the Norinyl 1+50 group (p less than .05) reporting breast discomfort. The lost to follow-up rate at 12 months was 19.3% for both the Norinyl 1+35 and the Norinyl 1+50 groups. The total discontinuation rate (including women lost to follow-up) at 12 months was 43.5% for the Norinyl 1+35 group and 41.0% for the Norinyl 1+50 group. There were no significant differences between the two groups for gross cumulative life table discontinuation rates (p greater than .05). There were six accidental pregnancies attributed to user failure reported during the study period; four in the Norinyl 1+35 group and two in the Norinyl 1+50 group.


Subject(s)
Contraceptives, Oral, Combined/adverse effects , Ethinyl Estradiol/adverse effects , Mestranol/adverse effects , Norethindrone/adverse effects , Adult , Drug Combinations , Female , Follow-Up Studies , Humans , Life Tables , Patient Dropouts
18.
Geburtshilfe Frauenheilkd ; 50(10): 806-9, 1990 Oct.
Article in German | MEDLINE | ID: mdl-1962751

ABSTRACT

This paper reports on four pregnancies with maternal liver tumors induced by oral contraceptives. No increase in size and no rupture of these liver lesions were observed during the gestational and postpartum period. The toxic potentials of orally active sex steroids and the role of natural sex steroids are discussed. Criteria for differential diagnosis and practical suggestions are presented.


Subject(s)
Adenoma/chemically induced , Carcinoma, Hepatocellular/chemically induced , Contraceptives, Oral/adverse effects , Liver Neoplasms/chemically induced , Pregnancy Complications, Neoplastic/chemically induced , Adenoma/diagnosis , Carcinoma, Hepatocellular/diagnosis , Contraceptives, Oral/administration & dosage , Ethinyl Estradiol/adverse effects , Female , Humans , Liver/pathology , Liver Neoplasms/diagnosis , Mestranol/adverse effects , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Prenatal Diagnosis
19.
Adv Contracept ; 6(2): 125-39, 1990 Jun.
Article in English | MEDLINE | ID: mdl-2206018

ABSTRACT

A comparative clinical trial of two combined oral contraceptives differing only in estrogen type and dosage was conducted at the Centro de Investigaciones Hideyo Noguchi in Merida, Yucatan, Mexico. The trial was designed to determine the differences between Norinyl 1 + 50 (Syntex) and Norinyl 1 + 35 (Syntex) in rates of discontinuation and frequency of selected side-effects which might contribute to method discontinuation. Three hundred women were randomly assigned to either the Norinyl 1 + 35 group or to the Norinyl 1 + 50 group and follow-up visits were scheduled at 1, 4, 8 and 12 months after admission. In the Norinyl 1 + 35 group, more women experienced an increase in intermenstrual bleeding (primarily staining and spotting) (p less than 0.05), breast discomfort (p less than 0.05) and nausea than in the Norinyl 1 + 50 group. There was a significantly higher discontinuation rate for personal reasons, such as desired change of method and method not needed, among the women taking Norinyl 1 + 35 (p less than 0.05). The largest number of discontinuations comprised women discontinuing for menstrual problems in both groups. The life-table total discontinuation rate at 12 months was 52.0 for the Norinyl 1 + 35 group and 50.7 for the Norinyl 1 + 50 group. The lost-to-follow-up rates at 12 months were 17.8 for the Norinyl 1 + 35 group and 22.8 for the Norinyl 1 + 50 group.


Subject(s)
Contraceptives, Oral, Combined/adverse effects , Contraceptives, Oral, Synthetic/adverse effects , Mestranol/adverse effects , Norethindrone/adverse effects , Adolescent , Adult , Contraceptives, Oral, Combined/administration & dosage , Contraceptives, Oral, Synthetic/administration & dosage , Drug Combinations , Female , Humans , Mastitis/chemically induced , Mestranol/administration & dosage , Mexico , Multicenter Studies as Topic , Nausea/chemically induced , Norethindrone/administration & dosage , Patient Compliance , Random Allocation , Uterine Hemorrhage/chemically induced
20.
J Reprod Med ; 35(5): 547-8, 1990 May.
Article in English | MEDLINE | ID: mdl-2352250

ABSTRACT

A prospective, randomized trial compared client experiences with three popular oral contraceptives--Triphasil, Ortho-Novum 7/7/7 and Ortho-Novum 1/35. After one year, no significant relationship was found between the contraceptive prescribed and either breakthrough bleeding or satisfaction with the medication. The monophasic formulation, Ortho-Novum 1/35, was associated with amenorrhea more often.


PIP: Differences in breakthrough bleeding, amenorrhea, and patient compliance among users of monophasic (Ortho-Novum 1/35) and triphasic (Triphasil and Ortho-Novum 7/7/7) oral contraceptives (OCs) were investigated in a prospective study at a Michigan family planning clinic. 377 (79%) of the women originally enrolled in the study completed the 1-year study period. There was no association between failure to return to the clinic at the required intervals and type of OC prescribed. The percentage of women experiencing breakthrough bleeding in their 1st year of use was 18.4% among Ortho-Novum 7/7/7 users, 17.8% among Ortho-Novum 1/35 users, and 11.2% among Triphasil users; the percentages of women reporting amenorrhea were 3.0%, 12.8%, and 0.0%, respectively. The degree of patient satisfaction was 82.8% for Ortho-Novum 7/7/7, 90.7% for Ortho-Novum 1/35, and 85.2% for Triphasil. No significant correlations were detected between age, weight, or height and the 3 variables under investigation. These findings indicate that Ortho-Novum 1/35, the monophasic formulation, is more frequently associated with amenorrhea than the triphasic OCs and that Triphasil seems to be most efficient in terms of establishing regular, dependable menstrual periods. However, neither breakthrough bleeding nor patient satisfaction were related to the brand of OC prescribed.


Subject(s)
Contraceptives, Oral, Combined/adverse effects , Amenorrhea/chemically induced , Drug Combinations , Ethinyl Estradiol/adverse effects , Ethinyl Estradiol-Norgestrel Combination , Female , Humans , Menstrual Cycle/drug effects , Mestranol/adverse effects , Norethindrone/adverse effects , Norgestrel/adverse effects , Patient Compliance , Prospective Studies
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