Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
 7,802 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Young women who use oral contraceptives over a period of years are prone to the development of hepatic tumors, which must be correctly diagnosed and treated. A 24-year old woman who had used various oral contraceptives (Neogynon 21, Lyndiol, Microgynon) for over 5 years developed a hepatocellular carcinoma of the left hepatic lobe. The diagnosis was reached on the basis of laboratory tests as well as the results of laparoscopic, angiographic, x-ray, sonographic, and scintigrammic examinations. An attempt to remove the tumor surgically resulted in a fatal mass bleeding. No metastiasis of the carcinoma could be established. An examination of the liver revealed an Australia-antigen-positive, chronic-aggressive hepatitis.
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PMID:[Malignant liver tumor after oral contraception]. 45

This investigation, using levonorgestrel, estimated the extent of a first-pass effect and established a pharmacokinetic model to describe drug concentrations after intravenous and oral administration. 3 women received 30 mcg of levonorgestrel in succession by intravenous and oral routes; another 6 were given 150 mcg (as Microgynon) in similar fashion. Radiolabeled levonorgestrel was used for intravenous administration of 30 mcg and oral administration for 150 mcg. Radioimmunoassay was used to determine plasma drug level after all treatments. Urine and feces eliminations were also recorded. After intravenous and oral administration, drug concentration and total plasma radioactivity declined in 2 disposition phases, with half-lives in the range of 1.5 hours/day. After intravenous administration, an early phase with a half-life of about 10 minutes was observed. Levonorgestrel was rapidly absorbed, with a half-life of about 20 minutes. Orally administered doses were completely absorbed. Intraindividual comparison showed that intravenous and oral administration of levonorgestrel is not subject to any first-pass effect.
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PMID:Investigations of pharmacokinetics of levonorgestrel to specific consideration of a possible first-pass effect in women. 64 45

The effects of norgestimate triphasic (Ortho Tri-Cyclen, Tri-Cilest) and levonorgestrel triphasic (Triphasil) formulations on lipid and androgen metabolism were assessed in a study of 66 healthy women who were treated through 6 menstrual cycles. Levels of the following were measured: cholesterol and its subfractions, triglycerides, carrier lipoproteins, estradiol, testosterone, and sex hormone binding globulin (SHBG). Comparison of baseline values after 3 and 6 months of treatment indicated that both regimens influenced lipid and androgen metabolism. There was a statistically significant between-regimen difference in the levels of high-density lipoprotein, which increased favorably with norgestimate triphasic but were reduced with levonorgestrel triphasic. Related data on SHBG showed that plasma levels of this marker of estrogen/androgen balance were increased significantly more in the norgestimate triphasic group, providing additional evidence of low androgenicity. Both regimens inhibited follicular growth to the same extent, as seen by low mean levels of estradiol in all of the on-therapy cycles. Both decreased free testosterone. Side effects in both groups were minor and characteristic of those observed with low-dose oral contraceptives (OCs). The results of the study support the reported safety and positive effects of norgestimate on lipid and androgen metabolism, in comparison with a levonorgestrel-containing combined OC.
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PMID:A comparison study of lipid and androgen metabolism with triphasic oral contraceptive formulations containing norgestimate or levonorgestrel. 132 55

Researchers from Gainesville, Florida compared data on 20 women who were randomly assigned the triphasic oral contraceptive (OC) Triphasil (ethinyl estradiol and levonorgestrel) with data on 24 women who were randomly assigned the triphasic OC Ortho-Novum (ethinyl estradiol and norethindrone) and data on 8 women who were controls to evaluate these 2 triphasic OCs' effects on coagulation and anticoagulation factors. They measured these factors at baseline and 6 and 12 months after beginning OC use. Both OCs significantly reduced prothrombin time (Triphasil at 6 and 12 months, p.001; Ortho-Novum at 6 months, p01, and at 12 months, p.001). They also decreased partial thromboplastin time (Triphasil at 6 months, p.01), and at 12 months, p.001; Ortho-Novum at 6 months, p.01). Both OCs significantly increased Factor XII after 6 and 12 months (Triphasil p.001 and p.01 for controls and p.05 from baseline, respectively; Ortho Novum p.01). Ortho-Novum considerably increased fibrinogen antigen at 6 and 12 months (p.05 and p.001 from baseline and p.05 for controls, respectively) while Triphasil increased it only at 12 months (p.05). Platelet counts remained the same. Ortho-Novum markedly increased antithrombin III activity after 6 months (p.05). Even though neither OC changed antithrombin III antigen, they did significantly increase alpha-1-antitrypsin antigen and plasminogen antigen and activity at 6 and 12 months as well as alpha-2-antiplasmin antigen at 12 months. Ortho-Novum increased alpha-s-antiplasmin antigen at 12 months. No great differences in coagulation or anticoagulation factors existed between the OCs. The mean values were within reference ranges. These results showed that the OCs had the same, limited effects on hemostasis and changes in coagulation factors offset changes in anticoagulation factors.
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PMID:Changes in coagulation and anticoagulation in women taking low-dose triphasic oral contraceptives: a controlled comparative 12-month clinical trial. 144 74

The purpose of prescribing combined oral contraceptives (OCs) is achievement of good cycle control and effective contraception with the least side effects, using an OC with the lowest possible dose of estrogen. Triphasil, Triquilar, Nordette, Microgynon 30, and Brevinor are good 1st choices because of the low estrogen dose (30-35 mcg). Women who probably cannot tolerate breakthrough bleeding and who need simple packaging should use a monophasic, more progestogenic OC, e.g., Nordette or Microgynon 30. Physicians should suggest a low dose estrogen and low dose antiandrogenic progestogen (OC) (e.g., Diane-35 ED) for women who have acne. They should advise patients that when they take OCs, their menstrual periods usually become shorter, regular, and lighter. Women need not take a break from OC usage. Vitamin C, antibiotics, griseofulvin, rifampicin, and anticonvulsants (except sodium valproate) interact with OCs. Women using warfarin and oral hypoglycemics and wanting to start using OCs need to consult their physician about changing requirements for warfarin and oral hypoglycemics. The effectiveness of OCs can be diminished by diarrhea and vomiting. Absolute contraindications to OCs include pregnancy, use during the first 2 weeks postpartum, history of thromboembolism, undiagnosed abnormal vaginal bleeding, focal migraine, coronary heart disease, steroid-dependent tumors, recent impaired liver function, and cardiovascular accidents. Some relative contraindications are older than 35 years old and smoking, breast feeding, and hypertension. This article provides a section on how to manage common side effects. For example, if the side effect is acne, the physician should prescribe an OC with increased estrogen and reduced progestogen (e.g., Triphasil/Triquilar to Biphasil/Sequilar). This article lists trade names of various OCs and their estrogen and progestogen doses, e.g., Nordette has 30 mcg ethinyl estradiol and 150 mcg levonorgestrel.
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PMID:Combined oral contraception. 147 9

A new form of postcoital contraceptive therapy is described as more effective because of reduced incidence of nausea, vomiting, and breast tenderness. Other forms of emergency contraceptive pills (ECPs) are the "Yuzpe" method or high-dose contraceptives. The new method calls for administration of 3 200-mg tablets of danocrine (Danazol) within 72 hours of unprotected intercourse and a second dose 12 hours later. There are mixed reviews of the efficacy of danocrine and ECPs. In one comparative study of ECP and danocrine use, efficacy of danocrine was greater but not significantly so. Another study found danocrine so ineffective that the study was halted. ECP use would not end unintended pregnancies caused by method failure unless it was condom failure. Estimates of ECP use involve 75% of the 1.7 million women with user or method failure, all 1.9 million women with unintended pregnancies from nonuse of contraceptives, and some of the 1.6 million abortion users. An obstacle to ECP use is lack of knowledge due to lack of Food and Drug Administration approval of Ovral and Danazol and physician concern for legal liability. Another obstacle consists in the logistics of obtaining ECPs and the fear of side effects. Provision of ECP kits with 3-5 regimens in clinic or physician offices is proposed for women without contraindications. Anticipated objections are reported to be encouragement of contraceptive risk taking, the health risks of repeated use, restrictions in Title X programs, and the drug effect on fertilization. Another proposal is to sell ECPs as over the counter drugs or in vending machines and changing US contraceptive prescription laws. Objections to elimination of the physician prescription requirement might be an increase in use among women with contraindications and a decrease in regular checkups and Pap tests. The objections could be overcome with proper package labeling. Paternalism is not a sufficient justification for requiring prescription of contraceptives and medical visits. ECPs, in fact, are already available as low dose contraceptives such as Lo/Ovral, Nordette, Levlen, Triphasil, and Tri-Levlen when 4 pills are used. Instructions for ECP use are given.
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PMID:Emergency contraceptive pills: a simple proposal to reduce unintended pregnancies. 148 31

This work was done in search for a model to examine target organ response to fluctuations in serum levels of sex hormone-binding globulin (SHBG) and its ligands. The time course and magnitude of fluctuations of SHBG, levonorgestrel (L-Ng), estradiol (E2), testosterone (T) and dihydrotestosterone (DHT) in serum were examined during and after treatment with 50 ug of ethinylestradiol (EE2) daily for 10 days in 10 volunteer women using NORPLANT implants. Six of these volunteers were also treated with 20 ug of EE2 daily for 7 days and two additional volunteers using a copper-T IUD were treated with 50 ug of EE2 daily for 7 days. In all cases, SHBG and L-Ng levels increased in a close parallel manner several-fold above basal levels during treatment, reaching a maximum around two days after the last EE2 pill. In contrast, the levels of E2 and T increased in one subject, decreased in 5 and remained unchanged in 4, while changes of DHT were unrelated to those of the other ligands. Since the L-Ng "secretion rate" by NORPLANT implants is constant, it follows that the effect of EE2 on its levels is due to a decreased metabolic clearance rate, most likely secondary to the increased binding of L-Ng to SHBG in serum. This interpretation is in agreement with the close parallelism in the fluctuations of L-Ng and SHBG. It is concluded that in NORPLANT users, SHBG and L-Ng, but not the endogenous ligands, behave in a predictable manner in response to EE2. Thus, this model affords the possibility of exploring the influence of SHBG on tissue response to progestins.
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PMID:Changes in serum levels of SHBG, endogenous ligands and levonorgestrel induced by ethinylestradiol in Norplant users. 151 7

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.
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PMID:Oral contraceptives and panic disorder. 759 8

We evaluated the impact of the menstrual cycle on auditory brainstem response (ABR) latency in nine normally cycling women. Subjects (age 23-40 years) using no hormonal therapy were recruited and underwent ABR testing during four different phases of the same menstrual cycle: early follicular (cycle days 1 to 3); mid-cycle (cycle days 12 to 15); mid-luteal (cycle days 17 to 22), and premenstrual (cycle days 25-27). Cycles were verified by basal body temperature, and serum estrogen (E2), progesterone (P), and gonadotropin levels. A control group of nine women (age 23-40 years) on oral contraceptives (Nordette-28) was also studied four times during a pill cycle. Results show a significant increase in the latency of wave III and wave V peak latencies and in the I-V interpeak interval associated with a high estrogen state at the mid-cycle phase. No statistically significant variations in latency were found in the birth control pill group. These data suggest the existence of brainstem auditory neural pathways that are sensitive to fluctuations in E2 levels during the menstrual cycle.
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PMID:Estrogen influences auditory brainstem responses during the normal menstrual cycle. 163 24

Of the contraceptive choices open to a post-partum woman with gestational diabetes, this discussion concentrates on low-dose oral contraceptives. Although gestational diabetes usually clears at delivery, 75% of these women will go on to developed impaired glucose tolerance or overt diabetes, especially if they are obese or if their glucose level had been high. Many elect permanent sterilization, but those requiring reversible contraception usually choose the IUD or the pill. IUDs carry a high risk of infection and are less effective in diabetics. The author compared a low-dose combined pill with 400 mcg norethindrone and 35 mcg ethinyl estradiol (Ovcon 35), and a pill containing levonorgestrel (Triphasil), to barrier contraception in 230 women with recent gestational diabetes. After 6-13 months of use 11-17% of each group had impaired glucose tolerance, and 15-20% of each group had diabetes (n.s.). Insulin levels rose from 28.5 mIU/mL to 59.7 in controls, 32.0 to 71.8 in Ovcon 35 users, and from 40.2 to 85.1 in Triphasil users (p0.05). HDL values rose significantly in the group taking Ovcon, and LDL values fell significantly in all 3 groups. These low-dose pills can be used safely in postpartum gestational diabetic women, as long as they do not smoke, are encouraged to lose weight, and have no sign of cardiovascular disease as evidenced by albuminuria and an ophthalmoscopic exam.
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PMID:Contraceptive options for the gestational diabetic woman. 167 21


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