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Ovarian follicular development during the use of oral contraception: a review.
Over the past 40 years, alterations to the composition of oral contraceptives (OCs) have been made in attempts to reduce adverse effects and to improve patient compliance while maintaining contraceptive efficacy. However, there is growing evidence to indicate that reducing the estrogen dose to minimize adverse effects may have compromised the degree of hypothalamo-pituitary-ovarian suppression, particularly during the hormone-free interval (HFI) or following missed doses. Follicle development during OC use appears to occur in association with a loss of endocrine suppression during the HFI. This information provides a rationale for reducing or eliminating the HFI in OC regimens. There is also evidence for an increased risk of follicle development and ovulation in women who use delayed OC initiation schemes, such as the "Sunday Start" method. It is not currently known why some follicles ovulate during OC use while others regress or form anovulatory follicle cysts. Continued research about follicle development during OC use would provide insight into understanding the precise mechanisms of action underlying combined OCs, as well as those of continuous OC formulations and emergency contraceptive regimens.
Contraceptives, Oral, Combined↗
Long-term reversible contraception with levonorgestrel-releasing Silastic rods.
Subcutaneously placed Silastic capsules containing levonorgestrel are effective for 5 years and have a higher continuation rate than other methods of reversible contraception. Six 3 cm capsules are required to achieve satisfactory circulating levels of levonorgestrel. Two 4 cm covered Silastic rods containing levonorgestrel, which are easier to manufacture, insert, and remove than the capsules, produce similar in vitro release rates. This study compared clinical and metabolic effects as well as bleeding patterns in 23 women using either six capsules (n = 11) or two covered rods (n = 12). Serum levels of levonorgestrel, lipids, and lipoproteins as well as frequency of elevated progesterone levels were compared in serum samples obtained before treatment and 1, 6, 12, 18, and 24 months after insertion with the two systems. While bleeding patterns were similar for users of the two systems, rod users had slightly higher serum levels of levonorgestrel and a lower incidence of cycles with elevated progesterone levels. Therefore, rods could replace capsules as a long-term, reversible contraceptive method.
Adolescent↗
[Use of oral contraceptives and risk of cancer, a cohort study].
BACKGROUND: Use of oral contraceptives and the risk of cancer continues to be an issue. MATERIAL AND METHODS: The Norwegian Women and Cancer Cohort Study was initiated in order to study the use of oral contraceptives and risk of cancer. A total of 102 443 women aged 31-70 were included from 1991 to 1997. In the follow-up analysis through 1999, 851 of the 96 355 eligible women had developed breast cancer, 171 ovarian cancer, 118 cervical cancer, 110 endometrial cancer and 219 colorectal cancer. RESULTS: The risk of breast cancer increased with the duration of oral contraceptive use (p for trend p = 0.002), while risk of ovarian and endometrial cancer decreased (p for trend p = 0.03 for endometrial cancer and p < 0.0001 for ovarian cancer). No significant association between the use of oral contraceptives and the combined risk of breast/endometrial/ovarian cancer was revealed. INTERPRETATION: Use of oral contraceptives does not seem to change the overall risk of cancer. The increased risk of breast cancer is compensated by the protective effect in relation to endometrial and ovarian cancer.
Adult↗
Breast cancer.
Several issues of clinical importance were in the forefront of discussion during 1989. Heated debates continue regarding whether alcohol, oral contraceptives or hormonal replacement therapy modifies a patient's risk for developing breast cancer. It is quite apparent, and rightfully so, that a major impetus in the arena of research in breast cancer seems to be towards cure of the disease. The rationale for offering adjuvant systemic treatment to a larger group of primary breast cancer patients who have a potential for cure certainly seems justifiable. However, one still needs to individualize patients based on their prognosis and objectively weigh the potential benefits and risks of adjuvant therapy in a given clinical situation, especially in patients with less than 1 cm primary tumors and negative axillary nodes as they have been shown to have a 20-year recurrence-free survival of 86%. A better understanding of several molecular and genetic parameters has begun. Further developments in this area may lead to clinically appropriate means of preventing or treating this disease. Metastatic disease continues to remain an incurable entity. Efforts aimed at treating metastatic disease with more 'intensive dose chemotherapy' have not been demonstrated to be beneficial for affected patients.
Adult↗
Users of reproductive health clinic services in a school pregnancy prevention program.
Although the potential of school-based programs in the prevention of adolescent pregnancy is well recognized, few have been evaluated. This paper describes the use of a reproductive health care clinic associated with a school pregnancy prevention program which had demonstrated success. The program operated in one junior and one senior high school in a large city during the 3 school years from 1981 to 1984. Three facets of the 818 users of the program clinic are explored: who enrolled in the clinic, why they enrolled and what contraceptive methods they received, and their continuation with the clinic. Chi-square analysis and Student's t-tests were used to test for significant differences between the two school and sex groups. Life table and regression techniques were employed to examine clinic continuation. The main findings are teens of both sexes used the clinic, and junior high males used it in surprisingly large numbers; there were no major school or sex differences in the characteristics of those who enrolled; most students enrolled to obtain a contraceptive method; although many females served by the clinic had previously used another family planning clinic, the majority of them had unmet needs; the rate of clinic continuation was high; and certain factors contributed to clinic continuation. These findings suggest that a clinic in a school-linked setting can successfully attract students to use its services and it may offer certain advantages for reaching sexually active teens in search of contraceptive protection.
Adolescent↗
Normalization of bone density in a previously amenorrheic runner with osteoporosis.
PURPOSE: To examine changes in bone mineral density (BMD) and bone mineral content (BMC) in relation to pharmacological and nutritional interventions in a distance runner diagnosed with the female athlete triad of disordered eating, amenorrhea, and osteoporosis. METHODS: BMD of the lumbar spine (L2-L4) and total proximal femur were measured from ages 22.9 to 30.8 yr using dual x-ray absorptiometry (DXA). RESULTS: At age 22.9, the patient presented with primary amenorrhea, low body weight (BMI: 15.8 kg.m(-2)), and low BMD in the spine (74% of normal, T score: -2.50) and hip (80% of normal, T score: -1.54). For the next 2 yr, the patient took oral contraceptives to induce menses, but continued to maintain a low weight. Her BMD remained unchanged. At age 25.1 yr, she decided to gain weight and improve her nutrition, resulting in small increases in spinal BMD (+1.1%), hip BMD (+1.6%), and total body BMC (+7.6%) in 4 months. From ages 25.4 to 30.8 yr, the patient continued to gain weight, eventually reaching a healthy BMI of 21.3 kg.m(-2); correspondingly, since baseline, her BMD had increased 25.5% in the spine and 19.5% in the hip, bringing her BMD to within normal values (spine: 94% of normal, hip: 96% of normal). CONCLUSION: This case illustrates that even if skeletal development is interrupted in adolescence, there is still the potential for "catch-up" in BMD well into the third decade of life. Reversal of large bone density deficits in this patient can be attributed to improved nutrition and weight gain but not to hormone replacement.
Absorptiometry, Photon↗
Retrospective, long-term follow-up study of the effect of a three-tier prescription drug copayment system on pharmaceutical and other medical utilization and costs.
BACKGROUND: Previous research has suggested that 3-tier prescription drug copayment systems produce drug cost savings without affecting the use of other medical services during the first 12 months after implementation. Assessment of such systems with a longer follow-up period has been needed. OBJECTIVE: This study examined the effect of a 3-tier copayment system on pharmaceutical and medical utilization and cost for 30 months after implementation in a population of commercially insured, preferred-provider organization members. METHODS: This was a quasi-experimental, pre-post with comparison group design that gathered data retrospectively from the claims database of a preferred-provider organization in the Midwestern United States. The intervention group comprised members whose employer switched from a 2-tier (generic/brand copayment) plan to a 3-tier (generic/formulary/nonformulary) plan. The comparison group comprised members whose employer retained the 2-tier plan. Employers did not offer a choice between the 2- and 3-tier plans. Outcome measures included total drug cost; net insurer cost (drug cost minus copayment); number of prescription claims; numbers of office visits, inpatient hospitalizations, and emergency department visits; and rates of continuation with chronic medication therapy. RESULTS: Relative to the comparison group (n=4132), the intervention group (n=3577) showed reduced growth in net cost and lower utilization of third-tier (nonformulary) medications (P<0.001 and P<0.01, respectively). The intervention and comparison groups did not differ significantly with respect to numbers of office visits, emergency department visits, or inpatient hospitalizations. Medication continuation rates were lower for the intervention than the comparison group at 6 months for oral contraceptives (P<0.05), but chronic medication therapy continuation rates did not differ significantly at any other time point or for estrogens, antihypertensives, or antihyperlipidemics. CONCLUSION: In the population studied, previous research findings were confirmed over a longer time period.
Adult↗
Reasons for first teen pregnancies predict the rate of subsequent teen conceptions.
OBJECTIVE: To identify reasons for inconsistent contraceptive use that antedate conception and continue to predispose participants in adolescent-oriented maternity programs to unsafe sexual practices after delivery. We hypothesized that teens who attributed their failure to use contraceptives before their first conception exclusively to concerns about their side effects and/or their own lack of motivation to prevent conception would report less consistent contraceptive use and more repeat conceptions than would teens who attributed their previous failure to use contraceptives to their lack of capacity to do so. METHOD: We conducted a 2-year, prospective, longitudinal study of contraceptive use and repeat conceptions in a racially/ethnically diverse population of poor 13- to 18-year-olds. The 198 study participants were enrolled consecutively during their first pregnancies from an adolescent-oriented maternity program. RESULTS: The majority (84%) of the teens attributed their failure to use contraceptives before their first pregnancy partially to a lack of capacity to do so. As hypothesized, these teen mothers were significantly more likely to use hormonal contraceptives (85% vs 62%), (particularly Norplant, 47% vs 19%) and less likely to conceive again (13% vs 41%). Most teens attributed their inconsistent contraceptive use during the postpartum study period to three factors: side effects, plans to abstain from sexual intercourse, and their lack of motivation to postpone additional childbearing. CONCLUSIONS: The reasons teen mothers give for not using contraceptives consistently before their first pregnancies predict the occurrence of subsequent conceptions during adolescence. Those who attribute their previous failure to use contraceptives consistently to side-effect concerns and their own lack of motivation to postpone childbearing are least likely to use hormonal contraceptives after delivery and most likely to conceive again. Our findings suggest that future research should focus on the development of more effective interventions for preventing repeat conceptions among adolescent mothers who had the capacity to prevent their first pregnancies.
Adolescent↗
Cyclic progestin administration brings about luteinization during continuous antiprogestin treatment.
The antiprogestin RU 486 has been proposed for use as a contraceptive because it disturbs folliculogenesis and inhibits ovulation when given continuously. In order to achieve regular and predictable withdrawal bleeding and to counteract the continuous influence of estrogen on the endometrium, a sequential, cyclic progestin regimen has been added. The drawback has been the frequent rise in the concentration of serum P, suggesting ovulation. The present pilot study with three subjects was carried out to test whether simultaneous administration of RU 486 and progestin during the second half of the cycle would eliminate the rise in serum P concentrations. Based on elevated serum P values, five of the seven cycles were apparently ovulatory. RU 486 alone, when given throughout the cycle at a dose of 8 mg per day without added progestin, resulted in anovulatory cycles, but the lengths of these cycles were prolonged. We conclude that both simultaneous and sequential cyclic co-administration of progestin with RU 486 abolishes the antiovulatory action of RU 486. This decreases the possibility of using antiprogestins in non-estrogenic contraceptive regimens (unless contraceptive effects of RU 486 exist at the endometrial level).
Adult↗
Contraceptive practice in the Philippines: a synthesis.
This article puts together all available data on contraceptive prevalence and effectiveness from 1968-83 in an attempt to assess the Philippine family planning program's performance in reducing fertility. 3 indicators of contraceptive effectiveness are discussed -- Pearl pregnancy rates, 12-month continuation rates, and effective protection level. Findings on factors associated with contraceptive prevalence are presented and discussed, with special emphasis on the effects of the Outreach project variables. The argument is that popualtion programs can influence demographic behavior, but the extent of this influence largely depends on the quality of program design and implementation.
Asia↗
Combined hormonal versus nonhormonal versus progestin-only contraception in lactation.
BACKGROUND: Contraception for women who are breastfeeding is a public health issue of global importance. Each year over 100 million women make decisions about beginning or resuming contraception after childbirth. These decisions include both the choice of contraceptive method and the time at which its use begins, both of which continue to be debated by experts. Choices of contraception may be limited for lactating women due to concerns about hormonal effects on quality and quantity of milk, passage of hormones to the infant, and infant growth. Ideally, the contraceptive method chosen should not interfere with lactation. Additionally, because the return of menstruation and ovulation can be unpredictable in breastfeeding women, the timing of contraception initiation is important. OBJECTIVES: To determine the effect of combined oral contraceptives and progestin-only contraceptives on lactation. The a priori hypothesis is that combined oral contraception impairs lactation, making it less appropriate than progestin-only or nonhormonal contraception for breastfeeding women. SEARCH STRATEGY: We used PUBMED, POPLINE, EMBASE, LILACS, and Cochrane Controlled Trials Register computer searches, supplemented by review articles and contact with investigators. SELECTION CRITERIA: We sought all randomized controlled trials, reported in any language, that included any form of hormonal contraception compared with another form of hormonal contraception, nonhormonal contraception, or placebo during lactation. Hormonal contraception could include combined oral or injectable contraceptives, progestin-only oral or injectable contraceptives, hormonal implants, or hormonal intrauterine devices. Study participants included breastfeeding women of any age or parity who desired contraception. DATA COLLECTION AND ANALYSIS: We evaluated the methodological quality of each report and sought to identify duplicate reporting of data from multicenter trials. We abstracted data onto data collection forms. Principal outcome measures included quantity of milk; biochemical analysis of milk composition; initiation, maintenance and duration of lactation; infant growth; efficacy of contraceptive method while breastfeeding; and timing of contraception initiation and its effects on lactation. Because the trials did not have uniform interventions, often lacked quantifiable outcomes, and had poor methodological quality, we could not aggregate the data in a meta-analyses. MAIN RESULTS: Seven reports from five randomized controlled trials met our inclusion criteria. Most of the five trials did not specify their method used to generate a random sequence, method of allocation concealment, blinding of treatments, or use of an intention-to-treat analysis. Additionally, high loss to follow-up rates invalidated at least two studies. The findings from two reports comparing oral contraceptives to placebo during lactation were conflicting. Another trial found no inhibitory effects on lactation from progestin-only contraceptives. Finally, the WHO trial found no effect of progestin-only contraceptives on lactation but a decline in breast milk volume from combination contraceptives during lactation. High loss to follow-up rates, however, undermine the credibility of the WHO trial. No significant differences in infant growth or weight appeared in any of the included trials as a result of the use of hormonal contraception during lactation. REVIEWER'S CONCLUSIONS: Evidence from randomized controlled trials on the effect of hormonal contraceptives during lactation is limited and of poor quality; results should be interpreted with caution. The existing randomized controlled trials are insufficient to establish an effect of hormonal contraception, if any, on milk quality and quantity. Evidence is inadequate to make recommendations regarding hormonal contraceptive use for lactating women. At least one properly conducted randomized controlled trial of adequate size is urgently needed to address this question.
Contraceptives, Oral, Combined↗
Contraceptive practices of female physicians.
To evaluate a potential bias between methods of birth control used and prescribed by physicians, we surveyed sexually active female physicians in regards to their own methods of birth control. When the contraceptive practices of female physicians are compared to those of the general population, no difference in use of various contraceptive methods is found. Among female obstetrician-gynecologists, however, the intrauterine device continues to be a disproportionally popular method of contraception. It is concluded that no gender bias exists in prescribing patterns of contraceptives since contraceptive use in female physicians is identical to that of the general populations.
Adult↗
Oral contraceptives and thrombosis. From risk estimates to health impact.
OBJECTIVE: The scientific debate on oral contraceptives (OCs) and thrombotic diseases continues unabated. The aim of this survey was to evaluate available scientific data on OCs and thrombotic diseases and to make tentative prescription recommendations of OCs to women with and without various thrombotic risk factors. CONSENSUS: In women 15-29 years old, venous thromboembolism is about twice as common as arterial complications. In women between 30 and 44 years, the number of arterial complications exceeds venous diseases by about 50%. The mortality from arterial diseases is 3.5 times higher than the number of deaths from venous diseases in women below 30 years, and 8.5 times higher in women 30-44 years old. A significant disability is more frequent in women suffering and surviving an arterial complication than in women with venous thromboembolism. Although many important scientific issues still have to be addressed, the available scientific data suggests a differential influence of OCs with second and third generation progestagens on the risk of venous and arterial diseases. OCs with second generation progestagens seem to confer a smaller increase in the risk of venous diseases and a higher increase in risk of arterial complications, compared with OCs containing third generation progestagens. The possible difference on the venous side seems to be smaller than primarily anticipated. RESULTS: Young women without any known risk factor for thrombotic diseases may use any low-dose OC. If OCs are prescribed to women with known risk factors for arterial thrombotic disease; e.g. smoking, diabetes, controlled hypertension, migraine without aura, family disposition of acute myocardial infarction (AMI) or thrombotic stroke, a low-dose pill with a third generation progestagen may have an advantage. If OCs are considered for women with risk factors for venous disease such as severe obesity, varicose veins, family history of VTE or with factor V Leiden mutation, a low-dose combined pill with a second generation progestagen may be preferable. In women above 30 years, OCs with third generation progestagens generally seem to confer less overall thrombotic morbidity, mortality and disability than OCs with second generation progestagens. These women should reconsider, however, the indication of combined OCs in the presence of significant risk factors of thrombotic diseases.
Adolescent↗
Past and current contraceptive use in Pakistan.
Despite a vigorous national family planning program and such innovations as the Continuous Motivation System, there has been little change in contraceptive use in Pakistan in recent years. Data from the 1968-69 National Impact Survey and the 1975 World Fertility Survey for Pakistan show that, while use rates increased by a small amount in urban areas, the rates in rural areas seem to have declined. Even in urban areas contraceptive use is low in comparison with other developing countries that began family planning programs around the same time. Although this is probably due to differences in economic development, further investigation of program structure and inputs is recommended.
Adolescent↗
The effect of continuous subdermal levonorgestrel (Norplant) on carbohydrate metabolism.
Blood glucose and plasma insulin levels during an oral glucose tolerance test were measured in 20 women using continuous subdermal levonorgestrel (Norplant) for contraception over a 12-month period. Changes in carbohydrate metabolism occurred as early as 1 month but were most marked after 6 months. After 1 month the area under the glucose and insulin curves increased by 12.3% and 37.7%, respectively. This increase was more marked by 6 months, but by 12 months it was significantly less marked. Although changes in the blood glucose and plasma insulin levels at different times during the oral glucose tolerance test occurred, they were all within normal limits for normal women. The peak blood glucose and insulin levels after insertion of the implant occurred 60 minutes after the glucose load, as opposed to 30 minutes before insertion. Apart from this, there was a significant delay in the return of these levels to fasting values. We conclude that this product, like any other progesterone-containing contraceptive, alters carbohydrate metabolism, but these alterations are not clinically significant in normal women. It is, however, possible that in potential cases of diabetes it may predispose to frank diabetes.
Adult↗
Generation and characterization of antibodies against synthetic peptides of porcine zona pellucida ZP3 alpha.
OBJECTIVE: Use of synthetic zona peptides as target immunogens is a promising approach to an anti-fertility vaccine. To elucidate contraceptive epitopes, we raised polyclonal antibodies against synthetic peptides of pig ZP3 alpha and evaluated for immunogenicity, ability to inhibit in vitro boar sperm-pig zona attachment, and cross-reactivity with human zonae. METHODS: Five synthetic peptides were chosen based on hydropathicity analysis of ZP3 alpha, synthesized and coupled to keyhold limpet haemocyanin (KLH). Pairs of male rabbits were immunized with each peptide-KLH conjugate using a multi-site intradermal injection protocol. Resulting antisera were evaluated for immunoreactivity with cognate peptide and ZP3 alpha/EBGD (purified endo-beta-galactosidase-digested ZP3 alpha), contraceptive potential using an in vitro pig gamete bioassay, and cross-reactivity with human zonae using indirect immunofluorescence. RESULTS: All anti-peptide-KLH sera demonstrated immunoreactivity with cognate peptide. Anti-peptide sera, except for anti-alpha-3-KLH serum, were less immunoreactive with ZP3 alpha/ EBGD. Antisera directed against alpha-1-KLH, alpha-2-KLH, and alpha-3-KLH demonstrated significant (P < .00001) inhibition of boar sperm-pig zona attachment. Only anti-alpha-2-KLH and anti-alpha-3-KLH sera cross-reacted with human zonae. CONCLUSION: Synthetic peptides of pig ZP3 alpha are immunogenic, elicit antibodies cross-reactive with human zonae, and have in vitro contraceptive activity. These data support continued investigation of synthetic ZP3 alpha peptides as potential target immunogens for anti-fertility vaccine development.
Amino Acid Sequence↗
A case of autoimmune progesterone dermatitis in an adolescent female.
BACKGROUND: Progesterone-induced dermatitis is a rare disorder. It typically occurs in females due to an autoimmune phenomenon to endogenous progesterone production, but can also be caused by exogenous intake of a synthetic progestin. Here, we present a case of autoimmune progesterone dermatitis (AIPD) seen in an adolescent female. CASE: The patient is a 15-year-old Caucasian female with no significant past medical history and no prior exogenous hormone use, who presented to her primary care physician complaining of cyclic skin eruptions. She noted that her dermatologic symptoms occurred monthly, just prior to her menses. An intradermal skin test using 0.1 cc of progesterone was performed. The patient immediately developed a wheal, confirming the diagnosis of AIPD. The patient was begun on a continuous regimen of an oral contraceptive pill with 30 micrograms of ethinyl estradiol and 0.15 mg of levonorgestrel. The skin eruptions have not returned since the initiation of this therapy. CONCLUSION: Autoimmune progesterone dermatitis manifests via the occurrence of cyclic skin eruptions. Women with the disorder commonly present with dermatologic lesions in the luteal phase of the menstrual cycle. Diagnosis of AIPD is confirmed by performing a skin allergen test using progesterone. Due to its rarity, AIPD should be considered a diagnosis of exclusion. In cases believed to be due to an endogenous production of progesterone, several methods of therapy have been attempted. The ultimate goal of therapy is the suppression of ovulation, which will prevent endogenous hormone production as progesterone is only produced in ovulatory cycles. Currently, the first-line choice of therapy is a combination oral contraceptive. If this treatment is ineffective, patients have been treated with danazol, gonadotropin releasing hormone analogs, tamoxifen, and oophorectomy with varying success.
Adolescent↗