Breast cancer and oral contraceptive therapy in premenopausal women

Patients with breast cancer were identified from the tumor registry at Wilford Hall USAF Medical Center for an epidemiological study. During the 1972-77 period, 242 patients with breast cancer were either diagnosed at or referred to the Center for therapy. The 117 of these who were premenopausal are the subject of this study. Ages and parities of the women are graphed. Almost 12% were current users of oral contraceptives at the time of diagnosis and almost 18% more had been users. The remaining 70% had never used oral contraception. The incidence of breast cancer in those women who had used oral contraceptives was lower than that expected in the population and was statistically significant at the p .05 level. Other investigators have found that the risk of breast cancer decreases with duration of oral contraceptive use. In addition, short-term mortality from the breast cancer was lower for the oral contraceptive users than for the other women in the study, probably due to earlier detection in connection with regular gynecological care. It is concluded that oral contraceptives possibly afford some protection from breast cancer.     

Evaluation and therapy of breakthrough bleeding in women using a triphasic oral contraceptive

This study was designed to investigate the incidence and pattern of breakthrough bleeding (BTB) in 1,259 women who were prescribed for the first time a triphasic oral contraceptive (OC, 7-7-7) and to evaluate a hypothesis of management for BTB persisting after three cycles. The new users were compared with a control group of 696 women who had used various OCs for at least 6 months. The incidence of BTB in the control group was 16.8% and in the new users was 24.9%, 17.5%, and 15.3% in the first 3 months, respectively. Breakthrough bleeding occurred late in the 7-7-7 package in 58% and early or midway through the package in 17% and 25%, respectively. We hypothesized that late-package BTB would improve if the patient was switched to a monophasic pill similar to the relatively estrogenic formulation of the beginning of the package and vice versa for early or midpackage BTB. Seventy women with BTB at 3 months were randomly given 0.5/35 or 1/35 for a further 3 months. Breakthrough bleeding was more likely (P less than 0.05) to improve in women switched to 1/35 compared with 0.5/35 regardless of where in the package BTB occurred.     

Effect of a desogestrel-containing oral contraceptive on the skin

Objective This pilot study evaluated the effects of a desogestrel-containing oral contraceptive (DSG-OC) on facial seborrhea (oiliness), acne and related factors in otherwise healthy women with moderate facial acne vulgaris.

Methods In this double-blind, placebo-controlled study, 41 women received DSG-OC (50/100/150 μg desogestrel plus 35/30/30 μg ethinylestradiol given in a 7/7/7 day regimen) and 41 received placebo for six cycles. Seborrhea and skin assessments, and hormone analyses were performed regularly.

Results Analyses of sebum output (measured using Sebutape®) indicated that the effect of DSG-OC on the skin varied with facial area. Compared with placebo, DSG-OC had a statistically significant effect on the cheeks (60% relative reduction in sebum output; p = 0.02), and a non-significant effect on the forehead (30% relative reduction in sebum output). Acne lesion counts did not differ significantly between groups. Both patient and investigator assessments of skin condition (visual analog scale) indicated significant improvements with DSG-OC compared with placebo. The reduced sebum output with DSG-OC is associated with a three-fold increase in sex hormone binding globulin, as well as an expected decrease in free testosterone and other androgens that were found in this group.

Conclusion These results suggest that DSG-OC reduces facial oiliness and may be a useful contraceptive choice for women with this problem.     

Effect of oral contraceptive therapy on the renin-angiotensin system in normotensive and hypertensive women

Plasma renin activity, plasma renin substrate (angiotensinogen), angiotensin I (AI), and plasma angiotensinase activity were measured in 8 women who had first become hypertensive during a mean 3.1 years on various oral contraceptives, and in 5 normotensive women, before and after 1 cycle of pills. All were determined by radioimmunoassay. 8 or more blood pressures were taken by 2 observers and averaged. Plasma renin activity increased from mean 2.12 to 3.52 ng/ml/hr (p greater than .2) in normal women, and from 3.0 to 5.06 in hypertensives (p less than .02). The mean plasma renin substrate values for both groups together rose from 1881 ng/ml to 4245 ng/ml. Angiotensin I rose from .029 ng/ml/hr to .049 in normals, and .027 to .037 in hypertensives. Mean plasma angiotensinase activity values rose from 3.6 to 5.4% degraded per minute in normal women and varied only from 6.5 before and to 5.9 after a pill cycle in hypertensive patients. The authors suggest that development of hypertension during oral contraceptive therapy may be due to abnormal inactivation of angiotensin.     

Effect of a desogestrel-containing oral contraceptive on the skin.

OBJECTIVE: This pilot study evaluated the effects of a desogestrel-containing oral contraceptive (DSG-OC) on facial seborrhea (oiliness), acne and related factors in otherwise healthy women with moderate facial acne vulgaris. METHODS: In this double-blind, placebo-controlled study, 41 women received DSG-OC (50/100/150 microg desogestrel plus 35/30/30 microg ethinylestradiol given in a 7/7/7 day regimen) and 41 received placebo for six cycles. Seborrhea and skin assessments, and hormone analyses were performed regularly. RESULTS: Analyses of sebum output (measured using Sebutape) indicated that the effect of DSG-OC on the skin varied with facial area. Compared with placebo, DSG-OC had a statistically significant effect on the cheeks (60% relative reduction in sebum output; p = 0.02), and a non-significant effect on the forehead (30% relative reduction in sebum output). Acne lesion counts did not differ significantly between groups. Both patient and investigator assessments of skin condition (visual analog scale) indicated significant improvements with DSG-OC compared with placebo. The reduced sebum output with DSG-OC is associated with a three-fold increase in sex hormone binding globulin, as well as an expected decrease in free testosterone and other androgens that were found in this group. CONCLUSION: These results suggest that DSG-OC reduces facial oiliness and may be a useful contraceptive choice for women with this problem.     

How to choose an oral contraceptive in 1984

The choice of currently available oral contraceptives (OCs) includes combined formulations in varying dosages and monophaic, biphasic, or triphasic form, sequential pills, synthetic progestin-only pills in macro or microdose, and injectable synthetic progestins. Before the advent of microdose pills, products were characterized by progestin or estrogen dominance. Rumors that microdose pills do not completely inhibit ovulation have hindered their acceptance in France, but research has shown that they inhibit ovarian secretions as effectively as more strongly dosed products. Their les profound inhibition of the hypothalamo-pituitary axis raises hopes of a lessened incidence of postpill amenorrhea. Progestin-only microdose pills allow considerable ovarian estrogen secretion, creating a veritable iatrogenic luteal insufficiency. Following the suppression of mestranol, the only estrogen used in OCs is ethinyl estradiol (EE). The only 19-norsteroid progestins which are fixed directly to the progesterone receptors are norethindrone and norgestrel; others such as lynestrenol, ethynodiol diacetate and norethindrone acetate are prohormones. Menstrual problems are among the most frequent side effects of minidose combined pills, but their incidence had dimished with the appearance of biphasic pills and the triphasic pills should offer even greater improvements. The frequency of thromboembolic venous accidents is firectly correlated to the estrogen dose of OCs, but arterial accidents and possibly arterial hypertension appear to be linked to the progestin dose. Synthetic progestins appear to diminish the high density lipoprotein (HDL) fraction of cholesterol and disturb glucose tolerance, while synthetic estrogens augment the HDL fraction of cholesterol and the very low density lipoprotein (VLDL) fraction of triglycerides, modify some coagulation factors, and elevate the plasma level of angiotensinogene. Dose levels and chemical structures of the constituents influence the metabolic effects of pill formulations. In current practice, minidose products are preferred because they cause fewer metabolic changes and are less likely to entail vascular risks. Sequential pills are prescribed for 1 cycle following induced abortion but are not used for long periods because they are not 100% effective, they carry a risk of endometrial hyperplasia, and they appear to increase risks of venous thromboembolism. A combination of 50 mcg EE and 2 mg cyproterone acetate may be prescribed for acne, and minidose combination pills may be used in case of fibroma or endometriosis. In case of contraindications to estrogen, a microdose or injectable progestin can be prescribed if their shortcomings are kept in mind. The current popularity of macrodose progestin-only pills in France has more to do with fashion than with science. All hormonal contraception should be avoided for women at risk, including smokers and those with hyperlipidemia or a family history of vascular accidents.     

Venous thromboembolism in relation to oral contraceptive use

The relation of the risk of venous thromboembolism to the use of oral contraceptives was assessed in a hospital-based study of 61 women suffering from a first episode of idiopathic deep vein thrombosis or pulmonary embolism (cases) and 1278 women admitted for trauma or respiratory infections (controls). Twenty (33%) of the cases and 121 (9%) of the controls had used oral contraceptives within the previous month, yielding an age-adjusted relative risk estimate of 8.1 (95% confidence interval 3.7 to 18) for recent users relative to never-users. For women using oral contraceptives containing less than 50 micrograms estrogen, the relative risk estimate was 11 (3.7 to 22); for preparations with 50 micrograms estrogen, it was 5.5 (2.1 to 15); and for preparations with more than 50 micrograms estrogen, it was 11 (3.9 to 30). Past use of oral contraceptives was not associated with an increased risk. The data suggest that the risk of venous thromboembolism is increased for recent oral contraceptive users relative to nonusers, even if women use oral contraceptives containing low doses of estrogen. Confidence intervals were wide, however, so that a reduction in the risk for users of lower dose formulations relative to users of higher dose formulations cannot be ruled out. Selection bias, if present, would have resulted in overestimation of the relative risk, but should not have distorted the comparisons according to dosage.     

Effect of age on the response of the hypothalamo-pituitary-ovarian axis to a combined oral contraceptive

Objective: To examine the effect of age on the response to treatment with a combined oral contraceptive.

Design: Prospective, controlled clinical study.

Setting: Reproductive medicine unit in a tertiary care university medical center.

Patient(s): Twenty-six healthy female volunteers aged 21–45 years.

Intervention(s): After a control cycle, all the women were given a combined oral contraceptive containing 20 μg of ethinylestradiol with 75 μg of gestodene for three cycles. The women were examined through the posttreatment cycle.

Main Outcome Measure(s): Pituitary and ovarian activity was assessed with ultrasound and measurement of ovarian steroids.

Result(s): Follicular activity was observed in all treatment cycles, although ovulation was inhibited. Ovarian suppression was maximal in cycle 1. Mean endogenous E₂ levels were lower during cycles 2 and 3 in the older group. Serum FSH levels were higher in the control cycle and on day 28 of the treatment cycles in the older group. Most women ovulated during the posttreatment cycle.

Conclusion(s): Combined oral contraceptives did not inhibit all ovarian activity; maximal suppression was seen in cycle 1. Less follicular activity was observed in cycles 2 and 3 in the older group. Raised FSH levels with age reflect increasing ovarian resistance to follicular development.     

Choosing the best oral contraceptive

This guide to choice of oral contraceptives, for U.S. clinicians, includes a review of the available types of pills, the pharmacology of the steroids in pills, safety issues regarding thrombosis, arterial disease and hypertension related to estrogens and progestins in pills, common side effects, and therapeutic uses of orals. Choice of an oral contraceptive narrows down to which of the 5 available progestins and their formulation, since all contain ethinyl estradiol as the estrogen. While Briggs' theory espoused picking a pill with the minimal metabolic effect, recent evidence suggests that some estrogenic activity may be preferable to the unopposed progestagen, actually an anti-estrogenic receptor effect, to prevent adverse lipid and blood pressure effects in users. Current pills with low doses of estrogens probably are not significant risks for women as regards thrombosis, particularly if predisposed women and smokers are excluded. Pills containing 0.35 mg ethinyl estradiol and 0.5 mg norethindrone, based on large population trials, are probably the minimal effective dose yet even these are more effective than most other contraceptive methods. Breakthrough bleeding and spotting have been further minimized, however, with multiphasic pills. It is best to start with a 0.30-0.35 mg estrogen oral contraceptive, such as Loestrin, Demulin, Orthonovum 1.35, Orthonovum 7/7/7 or Nordette, encouraging the patient to accept early side effects for 3 months before switching to others. Disorders that can be managed with oral contraceptives include recurring and pre-existing ovarian cysts, endometriosis, dysfunctional uterine bleeding and dysmenorrhea. Brief guidelines for handling normal side effects and treatment of the above disorders are included.