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Query: UMLS:C0020538 (hypertension)
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Restovar, a low dose combined oral contraceptive containing .75 mg lynestrenol and 37.5 mcg ethinyl estradiol was given to 83 women for up to 25 cycles or 1265 total. A cycle contained 22 pills begun on the first day of menstruation or withdrawal bleeding from previous pill cycles. Each woman was questioned regularly on side effects and bleeding, had weight and blood pressure taken, and received gynecologic exams before and after pill treatment. There were no pregnancies. Latency from end of the cycle to bleeding was 2-3 days in 87%; cycles lasted 28 days in 80%; bleeding lasted 3-4 days in 84%; flow was moderate in 72%; and spotting occurred in 4.2% of cylces and breakthrough bleeding in 2.4%; withdrawal bleeding was absent in 4.2% of cycles. The most common side effects were breast pain in 1.9% of cycles and headaches in 1.2%. These complaints as well as nausea, vomiting, leucorrhea, nervousness and depression were reported as less frequent or absent more often than present or aggravated. 6 women quit for drug related reasons. There was no significant weight change or hypertension (means 126/82 and 120/80 before and during Restovar. Thus this low dose pill is remarkably effective and well tolerated.
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PMID:[Clinical study of restovar, an oral contraceptive with a low estrogen content]. 114 76

A seminar held at the Coppleson Memorial Institute in Sydney, Australia, is summarized. The speakers were Dr. Michael Briggs, head of the School of Applied Sciences, Gordon Institute of Technology; Dr. Gordon Stokes, physician in charge of the cardio-renal unit, Sydney hospital; and Professor Victor Wynn, director, Alexander Simpson Laboratory for Metabolic Research, Saint Mary's Hospital Medical School, University of London. Dr. Briggs stated that current estimates show that 50 million women throughout the world are now using oral contraceptives (OCs). Metabolic changes produced appear to induce many of the troublesome side effects. Many of the side effects dependent on estrogens are dose-related. Several of the synthetic progestins act at a cellular level. Other progestational compounds, such as megestrol acetate and d-norgestrel, are biologically active de novo. The incidence of thromboembolic disease in women taking OCs is also dose-related to the estrogen content. With a combined tablet of 30 mcg of ethinyl estradiol and 150 mcg of d-norgestrel, efficacy is maintained, but at the expense of an increase in breakthrough bleeding. Assay of urinary-free cortisol is the best method of assessing tissue exposure throughout a 24-hour period to biologically active cortisol. Those taking the above noted dosages show no change in plasma or urinary-free cortisol levels. Dr. Stokes discussed the hypertensive response to oral contraception. The increased blood pressure, although usually small, is statistically significant. A smaller group has much more serious elevations of blood pressure. The hypertension is related to the estrogen content of the drugs used. It has been suggested that the increase in blood pressure may be related to estrogen-induced increased renin substrate. When activated, the renin substrate produces angiotensin which elevates blood pressure and increases aldosterone secretion. However, only 1-2% of women showing these changes develop hypertension. Some seem more sensitive than others to the changes. Professor Wynn stated that the 50 mcg of estrogen per day, usually given, is still too large a dose, 30 mcg being adequate. The 19-norsteroids are the most widely used group of synthetic progestins. The current concern is about metabolic effects. Impairment of carbohydrate tolerance may be important in some women. Study of plasma lipids shows elevation of triglyceride and cholesterol levels. Improvements that can be foreseen in the near future relate to adjustment of doses of presently available hormonal contraceptions especially of those known to cause metabolic effects.
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PMID:Metabolic effects of the pill. 115 23

One hundred fifty-seven pregnancies complicated by different degrees of diabetes, toxemia, and hypertension were studied with serial urinary placental estrogen determinations. A simple and fast method for total placental estrogen determination was used. The level of total estrogen excretion was related to Apgar score in cases of class B diabetes, severe toxemia, and also in moderate toxemia when estrogen excretion was falling. Mean estrogen levels did not differ as a function of severity of diabetes. Levels did differ with severity of toxemia; however, only the difference in mean estrogen excretion between mild and severe toxemia was significant. Estrogen excretion was very low in hypertension but was not related to Apgar score. This study concludes that total urinary estrogens constitute only a single parameter necessary in the management of high-risk pregnancies.
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PMID:Total urinary estrogens in complicated pregnancies. 116 30

The various contraceptive methods available and their suitability and contraindications in the case of diabetic patients are reviewed. After briefly discussing tubal sterilization, condoms, diaphragms and spermicides, and IUDs, and their respective safety and effectiveness, the risks and advantages of contraceptive steroids are analyzed in detail. It is concluded that the metabolic effects of estrogen-progestin combinations are more serious in many diabetics, and their use often increases the need for exogenous insulin, as well as the tendency to hyperlipemia, excessive weight gain, and hypertension, which are all factors that aggravate diabetes. The contraindications apply to cases of subclinical diabetes, because the administration of these drugs to genetically predisposed subjects may precipitate the appearance of clinical diabetes. Oral contraceptives should then be used only if IUDs are contraindicated in a specific case and the desire for future pregnancies precludes sterilization. Patients should then be carefully monitored, and the oral contraceptive used contain the smallest possible effective dose of estrogen (preferably ethinyl estradiol) and progestin (preferably other than the nortestosterone type of a 19-nortestosterone derivative in a very low dose).
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PMID:[Choice of a contraceptive method in the diabetic patient]. 121 58

Research and development in contraception has only limited interest in women over 35 years old, so we know little about safety, side effects, and effectiveness of contraceptives in this age group. In addition, clinical trials use healthy women which further limits our knowledge about contraceptives in women who have cardiovascular problems, diabetes, and liver conditions. Research does indicate, however, that women with high blood pressure should not take oral contraceptives (OCs) after the age of 35. It also shows that healthy and nonobese women over 35 who do not smoke and have no family history of cardiovascular disease before age 45 can take OCs with 30 mcg of ethinyl estradiol. Practitioners should provide these women with balanced and up-to-date information on the link between OCs and breast cancer and their apparent protective effect against endometrial cancer. The pregnancy rate for 35-39 year old married women using the diaphragm for at least 5 months stands at 1.1/100 women years. Contrary to popular belief, barrier methods can be harmful, e.g., urinary tract infections are more frequent in women who use the diaphragm than in those who do not. Women older than 35 should consider the condom because of its ability to reduce the risk of acquiring HIV or sexually transmitted diseases. Considerable research exists on women over 35 who use copper releasing IUDs. These IUDs are safe in women who do not have heavy menstrual bleeding. The levonorgestrel releasing IUDs are well tolerated in women over 35 since they reduce the amount and duration of menstrual bleeding. Besides users of these IUDs are less likely to have pelvic inflammatory disease and endometritis than those using copper releasing IUDs. Older women in developing countries often undergo hysterectomy for contraceptive purposes and because of heavy bleeding. Tubal ligation is a significant family planning method for older women in developing countries.
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PMID:Contraception after thirty-five. 131 37

The effectiveness of monophasic and multiphasic oral contraceptives (OCs) depends on their ability to suppress ovulation, change endometrial growth and ovum receptivity, and reduce cervical mucus receptivity to sperm. They are all more than 99% effective, but, depending on the type and dose of hormone components, they have different side effects. The estrogen component (ethinyl estradiol) of most new OCs is between 30 and 35 mcg, which reduces the risk of estrogen side effects, especially thromboembolism and hypertension. The Food and Drug Administration does not recommend use of an OC with an estrogen component for lactating mothers, while the American College of Obstetrics and Gynecology and the American Academy of Pediatrics believe it is fine. Estrogen may protect against coronary artery disease, yet the estrogen component of today's OCs is so low that the progestin component may cancels this beneficial effect. It also prevents breakthrough bleeding. The most frequently used progestins in OCs are norethindrone and norgestrel. They prevent ovum implantation, sperm penetration through the cervical mucus, and ovulation. Progestins, especially norgestrel, increase the risk of coronary artery disease. Other side effects include acne and weight gain. Progestin benefits are reduced menstrual blood loss, pain during menstruation, premenstrual tension, and endometrial cancer risk. The ideal estrogen-progestin balance depends on the individual, but the estrogen component should be between 30 and 35 mcg, and the progestin component should be the lowest possible dose to reduce metabolic side effects. If an OC user with a well stabilized cycle who takes another recently prescribed drug experiences unexpected breakthrough bleeding or spotting, this change may indicate a drug interaction. Absolute and/or possible contraindications of OC use are smoking after age 35, history of breast or endometrial cancer, liver disease or impaired liver function, cardiovascular risk factors, and diabetes mellitus.
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PMID:Benefits and risks of oral contraceptive use. 143 13

Epidemiological data have revealed that the progestogen in oral contraceptives (OCs) is involved in hypertension, ischemic heart diseases, and stroke. Atherosclerotic lesions were implicated owing to the androgenic properties of progestogens. However, atherosclerosis did not develop despite reduced high density lipoprotein (HDL) and elevated low density lipoprotein (LDL), presumably because of the strong effect of ethinyl estradiol (EE) upon induction of hepatic LDL- and remnant-receptors. A series of findings indicate that vasospasms caused by the effect of progestogens are involved in arterial thromboses. In postmenopausal women, the addition of progestogens to the estrogen treatment may trigger ischemic diseases. Estrogens exert a vasodilatory effect and stabilize the vascular tonus through the responsiveness of the endothelium, neurotransmitter release, and direct blocking of calcium channels. Progestogens increase the sensitivity of arteries to vasoconstrictory compounds and reduce blood flow. In women treated with ovulation inhibitors, and EE-induced activation of the renin-angiotensin-aldosterone system was observed. Aldosterone acts vasodilatorily, while progestogens with high affinity to the aldosterone receptor may exert a strong vasoconstrictory effect. If vascular lesions are present, the vasoconstrictory action of progestogens may cause acute ischemic attacks. Therefore, the lowest effective dose of the progestogen has to be used for replacement therapy. In hysterectomized women, the extra administration of progestogens should be avoided and in women with arterial diseases they should be prescribed with discretion. Additional progestogens given for 14 days 3 months apart may suffice for the prevention of endometrial hyperplasia. Both the EE and progestogen doses in OCs should be reduced. Progestogen-dominant ovulation inhibitors should be restricted to cases with an additional indication.
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PMID:[Hormonal contraception and substitution therapy: the importance of progestogen for cardiovascular diseases]. 145

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

The forms of administration, mechanisms of action, side effects and complications, and other aspects of female hormonal contraception are set forth in this "lesson" for medical students. Female hormonal contraception has been in use for over 30 years and is used by more than 150 million women worldwide. Oral contraceptives suppress the preovulatory peak of follicle stimulating hormone and luteinizing hormone, preventing ovulation and follicular maturation. Progestins render the cervical mucus impermeable to sperm and modify the endometrium so that it will no longer support implantation. The synthetic estrogen ethinyl estradiol is used in most combined oral contraceptives (OCs). Among the numerous progestins in use are the newer desogestrel, gestodene, and norgestimate, which have fewer androgenic and metabolic effects than did the 1st generation. the different forms of administration of hormonal methods include combined OCs, oral preparations containing low doses of progestin continuously administered or high doses continuously or discontinuously administered. Intramuscular injection of progestins and the so-called "morning after" postcoital pills are less often prescribed. The combined preparations may be monophasic, biphasic, triphasic, or sequential. Sequential preparations should be avoided because of the hyperestrogenic climate they induce. The low-dose progestin preparations are indicated for women with contraindications to synthetic estrogen. They must be taken at the same time each day and have a relatively high rate of side effects, especially ovarian and breast cysts and irregular bleeding. High-dose progestin preparations have significant metabolic effects and are indicated primarily for patients with gynecological problems such as fibromas and endometriosis. Intramuscular injection of medroxyprogesterone acetate every 3 months is effective but has the same side effects as high-dose progestins. It is indicated primarily for patients unable to control their own behavior. The hormonal methods are all highly effective in preventing pregnancy when correctly administered. Side effects may be minor problems, such as nervousness and nausea, that are usually of short duration. the more serious side effects, including modifications of lipid or carbohydrate metabolism, hemostasis, blood pressure, or hepatic functioning and cardiovascular effects, have been reduced with the new lower dosed formulations. Absolute contraindications to hormonal contraception include undiagnosed vaginal bleeding or amenorrhea, history of thromboembolic or cerebral vascular accidents, severe cardiopathy or hypertension, hyperlipidemia, hepatopathy, hormonodependent cancer, pituitary tumors, porphyria, and severe mental problems. Relative contraindications impose the need for careful monitoring and follow-up. The practitioner should be aware of the possibility of interactions between OCs and certain other drugs.
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PMID:[Hormonal contraception]. 160 74

The significance of antibodies against ethinyl estradiol (anti-EE-Ab) and other risk factors was discussed for a series of 1318 cases of venous and arterial thrombosis in oral contraceptive users, in comparison to 61 non-users and 124 health current pill users. The cases included 264 deep vein thromboses, 159 pulmonary embolism, 37 coronary artery, 33 systemic artery, 763 cerebrovascular artery thromboses, and 10 hepatic vein thromboses collected from 88 French hospitals from 1976-1988. There were 98 cases with successive or multiple sites involved. The mean age of contraceptive users with thrombosis was 32.1, compared to 28.8 in healthy users. Duration of use was slightly longer in affected users than healthy users, but some cases were affected as early as their 1st cycle. 87.2% had no related history. The anti-EE-Ab were absent in never users, averaged 318 c./min in pill users with thrombosis, but 60 in healthy pill users. There was no correlation between anti-EE-Ab level and dose or duration of pill use. Similar anti-EE-Ab levels were found in those with venous or arterial thrombosis, but women with arterial thrombosis were older, had used pills longer, had fewer predisposing factors of surgery or labor and delivery, but more frequent incidence of hyperlipidemia, smoking, and hypertension. The most frequent associated factors with thrombosis were presence of anti-ee-Ab and smoking: 15.6% smoked, 31.1% had anti-EE-Ab, and 47.6% had both, but only 9.5% had neither factor. It is interesting that lowering the estrogen dose of oral contraceptives has decreased the frequency of venous thrombosis, but not that of arterial thrombosis or mortality, nor anti-EE-Ab levels. The vascular lesions in arterial thrombosis seen in pill users are thought to resemble those in many autoimmune diseases.
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PMID:Oral contraceptives, sex steroid-induced antibodies and vascular thrombosis: results from 1318 cases. 178 53


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