Contraception

Contraception
  

• J Trussell, B Vaughan (Princeton Univ,NJ) 
  Contraceptive Failure, Method-related Discontinuation and Resumption of Use; Results From the 1995 National Survey of Family Growth.
  Fam Plann Perspect 31:64-72 & 93, 1999.
     
  The study concludes that during typical use of reversible methods of contraception, the risks of pregnancy are considerably higher than risks of failure during clinical trials. This outcome reflected imperfect use of these methods rather than the lack of inherent efficacy. Dissatisfaction with available methods was probably reflected in the high rates of method-related discontinuation.
      
  Editorial comments that except for implants and the intrauterine device, failure rates of most contraceptive methods in typical use are higher than in clinical trials because the methods are not used consistently and correctly.
     

• V Beral, et al (Radcliffe Infirmary, Oxford, England; Parkway Hosue, Manchester, England) 
  Mortality Associated with Oral Contraceptive Use: 25 Year Follow Up of Cohort of 46000 women from Royal College of General Practitioners’ Oral Contraception Study.
  BMJ 318:96-100, 1999.
      
  The study concludes that the main effect on mortality by oral contraceptives appears during use and in the 10 years after use ceases. Similar mortality is found among never users and those who stopped using contraceptives 10 or more years earlier.
     
  The results of the data analyzed in this study are reassuring for women who used high estrogen dose oral contraceptives (OC). Ten or more years after stopping OCs, mortality rates for all causes, as well as most specific causes, were similar in women who had and those who had not used OCs. Particular interest is the fact that the mortality rate for breast cancer was nearly identical in OC users and nonusers. Mortality rates for ovarian and uterine cancer were lower in the OC users than nonusers, while ingesting OCs need to have annual cervical cytology because they have an increased risk of developing cervical cancer compared with OC nonusers.
     

• Weight change with Oral Contraceptive Use and During the Menstrual Cycle : Results of Daily Measuremetns. 
  M Rosenberg (Health Decisions Inc, Chapel Hill, NC) 
  Contraception 58:345-349, 1998.
     
  Weight gain is a common reason for women’s discontinuation of oral contraceptives (Ocs). However, relatively few studies have investigated the association between weight gain and OC use.
     
  128 women were studied for the purpose for 4 cycles and found that oral contraceptive use appears to be unassociated with weight gain. Women concerned about weight gain with OC use should be counseled that this appears to be a misperception.
     
  The weight gain probably mainly due to other factors such as exercise, eating patterns, or lifestyle changes and not to OC use.
     

• Myocardial Infarction and Use of Low-dose oral contraceptives; A Pooled Analysis of 2 US Studies.
  S Sidney, et al (Kaiser Permanente med Care Program, Northern California: Univ of Washington, Seattle; Natl Inst of Child Health and Human Development, Bethesda, Md; et al) 
  Circulation 98:1-6, 1998.
     
  Conclusion: There was no evidence of increased risk of myocardial infarction with OC use in either study, even though the number of smokers, those with risk factors for cardiovascular disease, and those older than 40 were small.
      
  Oral contraceptives with 50mg of estrogen or more were associated with an increased risk of myocardial infarction (MI) in women who smoked cigarettes, but not in nonsmokers. The etiology of the MI in these women was enhanced thrombosis, not atherosclerosis. The thrombophillic effects of OCs are directly related to the amount of estrogen in the formulation. Nearly all OCs now used in the United States have between 20 and 35mg of estrogen. Furthermore, in the US, OCs are not currently prescribed to women older than 35 who smoke cigarettes or to those of any age with uncontrolled hypertension. As shown in this analysis, use of these low-dose formulations and avoidance of OC use in women with certain risk factors for MI appears to have eliminated any increased risk of MI with OC use. It remains to be determined whether the decreased risk of MI associated with past use of OCs is casually related to their use.
     

• SM Schwartz, et al (Univ of Washington, Seattle; Southern California Permanente Med Group, Pasadena, Calif; KP Med Care Prgoram, Oakland, Calif; et al) 
  Stroke and Use of Low-dose Oral Contraceptives in Young Women: A Pooled Analysis of Two Studies.
  Stroke 29:2277-2284, 1998.
      
  It was concluded that an increased risk of stroke was not found among women who use low-dose oral contraceptive pills. The risk of stroke among users needs to be clarified with further studies on the basis of age, smoking, obesity, hypertension, or migraine history.
      
  Editorial comments: Combining the data from 2 large case-control studies in the states of California and Washington indicates the risk of developing either ischemic or hemorrhagic stroke is not increased with the use of low-dose oral contraception.
     
  Lowering the dose of steroids in the formulations as well as not prescribing oral contraceptives to women older than 35 who smoke as well as those with uncontrolled hypertension has eliminated stroke as a risk of taking oral contraceptives. The data showing an increased risk of stroke in women with migraine headaches who take oral contraceptives is of some concern, because nearly 20% of reproductive age women have migraine headaches. Many authorities recommend prescribing oral contraceptives to women with common migraine but not classic migraine. Classic migraine is when peripheral neurologic symptoms or visual disturbance occurs.
     

• K.Michaelson, et al (Univ Hosp, uppasala, Sweden; Dartmouth Med School, Hanover, NH; Karolinkska Inst, Stockholm) Oral-Contraceptive Use and Risk of Hip Fracture : A Case -Control Study.
  Lancet 353:1481-1484, 1999.
     
  All cases of hip fracture occurring between October 1993 and February 1995 among women born after 1913 were identified.
      
  It was found that use of oral contraceptives after age 40 years decreased the risk of hip fracture, whereas their use before age 30 years did not. Use between the ages of 30 and 40 years conferred a moderate degree of protection.
     
  Editorial comments: One of the noncontraceptive health benefits of oral contraceptive (OC) use is increased bone density compared with never use of OCs. The results of this epidemiologic study indicate that use of high estrogen dose OCs (50 mg or more) after age 40 appears to significantly reduce the risk of subsequent hip fracture. Very few women are currently using oral contraceptives with 50 mg of estrogen. It remains to be determined whether taking OC formulations with 20 to 35 mg of estrogen in the perimenopausal period also reduces the risk of having a hip fracture later in life.
     

• NR Poulter, for the World Health Organization Collaborative study of Cardiovascular Disease and Steroid Hormone Contraception (St Mary’s Hosp. London)
  Cardiovascular Disease and Use of Oral and Injectable Progestogen only Contraceptives and Combined Injectable Contraceptives: Results of an International Multicenter, Case-Control Study.
  Contraception 57:315-324, 1998.
     
  Conclusion: There is little or no increased risk of stroke, venous thromboembolism, or acute myocardial infarction associated with the use of oral or injectable progestogen-only contraceptives or combined injectable contraceptives. There may be a need, however, for further studies on the possible adverse effects on stroke risk of progestogen-only contraceptives taken by women with a history of high blood pressure.
     
  The mechanism whereby combined oral contraceptives increase the risk of venous thrombosis as well as ischemic stroke and myocardial infarction in women with risk factors is from a thrombophillic action of the estrogen component of these agents. Because the progestin component, unlike ethinyl estradiol, does not increase hepatic synthesis of globulins involved in the coagulation process, one would not expect the use of progestin-only contraceptives would increase the risk of having an adverse cardiovascular event. The results of this large epidemiologic study provide data indicating use of either oral or injectable steroid contraceptives containing a progestin without estrogen is not associated with a significantly increased risk of venous thrombosis, stroke, or myocardial infarction. Although product labeling states progestin-only contraceptives should not be used in women with a history of venous thrombosis, no data indicate that these agents alter the risk of venous thrombosis among women with a history of this disorder.
     

• 1. Spinal Bone Density in women using Depot Medroxyprogesterone Contraception.  
  T Cundy, et al Univ of auckland, New Zealand) Obstet Gynecol 92:569-573, 1998.
  2. Bone Density in Long term users of depot Medroxyprogesterone Acetate. B Gbolade, et al (Univ of Manchester, England) Br J Obstet Gynaecol 105:790-794, 1998.
  3. Bone Density Among Long-term users of Medroxyprogesterone Acetate as a Contraceptive. LC Paiva, et al (Universidade Estadual de Campinas, Sao Paulo Brazil) Contraception 58:351-355, 1998.
  4. Bone Mineral Density in women using Depot Medroxyprogesterone Acetate for Contraception. D Scholes et al (Univ of Washinghton, Seattle) Obstet Gynecol 93:233-238, 1999.
  5. Long-term Depot Medroxyprogesterone Acetate and Bone Mineral Denstiy. OS Tang, et al (Univ of Hong Kong, China) Contraception 59:25-29, 1999.
      
  The above five articles have been published in the recent years and results of use of Depot Medroxyprogesterone Acetate (DMPA) and the bone mineral density. 5 observational studies performed in 5 different countries with women of different ethnic groups, indicate that the use of DMPA is most likely associated with some degree of bone loss. The amount and location of the bone loss varied in the different studies, as well as the age groups most likely to experience this problem when using DMPA. Although there are scant data, the bone loss appears reversible after stopping use of DMPA. There are also no reports of an increased risk of fractures in DMPA users. It would appear useful to encourage calcium intake of 1,500 mg/day in adolescent DMPA users and to consider performing a bone scan in women who have used DMPA for 5 or more years to determine whether they have a decreased amount of Bone Mineral Density (BMD).
     

• A Multicentre Efficacy and Safety Study of the Single Contraceptive Implant Implanon.
  HB Croxatto, and the Implanon Study Group (Chilean Inst of Reproductive Medicine, Santiago, Chile; et al ) Hum Reprod 14:976-981, 1999.
     
  Implanon, a single-rod contraceptive implant made of an ethylene vinyl acetate copolymer, contains a core with 68 mg of etonogestrel, which inhibits ovulatin for 3 years. The implant is 40mm long, has a diameter of 2mm, and comes in a sterile disposable insert for subdermal application. The contraceptive reliability of this implant was tested in an open, multicenter study.
     
  It was found that Implanon has excellent contraceptive action in its 3-year lifetime. The safety profile, similar to that of progestogens in general, is acceptable.
      
  The main advantage of this single subdermal contraceptive implant is its small diameter (2mm), which allows it to be easily and rapidly inserted through a disposable insertion trochar without the necessity of performing a skin incision. The rods and capsules containing levonorgestrel are 2.4 and 2.5mm in diameter, and a skin incision is necessary before insertion of the trochar containing these implants. The single implant releasing etonogestrel is effective for 3 years, whereas the levonorgestrel impalnts are effective for 5 years. Removal rates because of bleeding problems (19% at 2 years) are higher for the single implant than those reported for the levonorgestrel implant (11% and 12% at 3 years); however, the participants and clinicians differed in the 2 studies, so one cannot conclude that the differences are due to the contraceptive method instead of other factors, such as preinsertion counselling. It is encouraging that 2 additional very effective reversible long-acting methods of contraception are now available.
     

•  von Hertzen, for theTask Force on Postovulatory Methods of fertility Regulation (WHO, Geneva) 
  Randomised Controlled Trial of Levonorgestrel Versus the Yuzpe Regimen of Controlled Oral Contraceptives for Emergency Contraception. 
  Lancet 352: 428-433, 1998.
     
  The Yuzpe regimen for emergency contraception consists of ethinylestradiol 100mg plus levonorgestrel 0.5mg or dl-norgestrel 1.0mg, repeated after 12 hours. Although this rigmen is widely used, more effective and better-tolerated approaches are needed. A previous trial suggested that treatment with levonorgestrel 0.75mg, repeated after 12 hours, might offer more effective contraception with a lower rate of nausea and vomiting. These 2 approaches to emergency contraception were compared in a multicenter trial. With the conclusions that Levonorgestrel appears to be a more effective and better tolerated approach to emergency contraception than the Yuzpe regimen, which is currently the standard treatment. With either treatment, the risk of pregnancy increases with increasing time before treatment. The levonorgestrel regimen should help to make emergency contraception more acceptable.
     
  The author suggests that in contrast to an earlier summary of results of studies of emergency contraception, effectiveness was greater when the agents were given within 24 hours of sexual intercourse than when they were given in the subsequent 48 hours period.
     

• D von Hartzen, for the Task Force on Postovulatory Methods of Fertility Regulation (WHO), Geneva 
  Comparison of Three Single Doses of Mifepristone as Emergency Contraception: A Randomised Trial.
  Lancet 353;697-702, 1999.
     
  Mifepristone administered in a dose of 600mg within 72 hours of unprotected coitus has been associated with no pregnancies under ideal conditions. The effectiveness and side effects of lower doses of mifepristone (50mg and 10mg) and a longer postcoital treatment period (up to 120 hours) were examined in a randomized, controlled trial conducted in 11 family planning clinics in 6 countries on 4 continents.
    
  Conclusion derived from this study was that lowering the dose of mifepristone 60-fold did not compromise its effectiveness as an emergency contraceptive under typical use. There were fewer disturbances in the menstrual cycles with lower dose of mifepristone.
     
  Editorial comments: Two previous randomized, controlled trials found that ingesting a single 600-mg dose of mifepristone is as effective, and possibly more effective, as ingesting the standard Yuzpe regimen of 2 tablets of the oral contraceptive containing ethinyl estradiol and levonorgestrel on 2 occasions 12 hours apart. The results of this large, randomized trial indicate that a single tablet of 10mg of mifepristone prevents pregnancy as well as a single 600-mg dose. Thus, when mifepristone becomes available, a small dose of this agent can be used as an emergency contraceptive and prevent about 85% of expected pregnancies, slightly better than the 75% prevention rate with the Yuzpe regimen.
      

• Anne Szarewski, (Sr.Clinical Rsearch Fellow in Gynaecological Oncology, Department of Mathematics, Statistics and Epidemiology, UK)
  What’s new in contraception ?
  John Studd – Progress in Obstetrics and Gynaecology, 14th ed.
      
  The ideal contraceptive would be 100% effective, with no health risks or side effects, independent of intercourse, easily and completely reversible, easily administered and used independently of the medical profession. However, such a method does not yet – and may never – exist. In practice there is, therefore, a trade-off between efficacy and safety.
      
  THE COMBINED PILL
  Four years have now elapsed since the UK committee on Safety of Medicines (CSM) issued its statement about the risk of venous thrombo-embolism (VTE) with second and third generation oral contraceptive pills. During those 4 years, the one undisputed fact is that the termination rate in England and Wales rose by at least 8% following the scare.
      
  VTE is rare in young women, with the incidence estimated at being around 5 per 100,000 per year. The risk in pregnancy is higher, at 60 per 100,000 per year. The risk in women using pills containing the progestogens, desogestrel and gestodene, had a risk of VTE of 30 per 100,000 per year. In 1995, the CSM advised doctors that, because second generation pills now appeared, in these studies, to have a reduced risk, of 15 per 100,000 per year, desogestrel and gestodene-containing pills should no longer routinely be used as first choice contraceptives.
     
  Later studies, which were better able to control for other variables show no difference between second and third generation pills. However, given that the absolute risk of both incidence and mortality, whichever figure is taken is so small that this is essentially a legal, rather than a medical issue.
     
  Third generation pills have other benefits such as good cycle control, are less androgenic than second generation products and therefore, tend to be better for women who have problems with acne, hirsutism, and weight gain. A Norgestimate containing pill, which has not been evaluated in the three studies of VTE risk, has recently been licensed by the US FDA for the treatment of acne.
      
  The risk of breast cancer in oral contraceptive users has been the topic of a number of pill scares in the last 15 years. A recent overview of 90% of the studies so far carried out suggests a small increase in risk (relative risk 1.24) for women who are current users of oral contraceptives. But tumors, which have been detected have been early and well differentiated. In the end it comes to that mortality from breast cancer might actually be reduced in pill users and the risk is reduced after stopping the pill and there is absolutely no risk 10 years after stopping the use.
     
  It is possible that the so-called increase risk is due to the breast awareness and that the women who are on pills are more likely to be seeing doctors and nurses regularly.
     
  EMERGENCY CONTRACEPTION
  The Yuzpe hormonal regimen, consisting of 100 µg ethinyloestradiol plus 500 µg levonorgestrel, repeated 12 hr later, is well established. Provision of emergency contraception to women would obviously be useful to couples using barrier methods, but one should not forget that women using the pill sometimes forget to restart a packet on time (or miss a number of pills) and would, therefore, also benefit from a reserve packet of the emergency pill.
     
  A study has been published in which 1998 women were randomly assigned either to the Yuzpe regimen or to receive levonorgestrel 750 ug, repeated 12 hr later. The failure rates were 3.2% and 1.1% respectively.
     
  The more surprising finding was that the efficacy of both methods was significantly greater if they were commenced within 24 h of coitus. The levonorgestrel regimen has been recently licensed in the UK as Levonelle-2. This consists of two tablets each of 750ug of levonorgestrel, to be given 12 h apart.
     
  Amidst all the arguments about hormonal methods, it should not be forgotten that, at present, the most effective emergency contraceptive is still the insertion of a copper intra-uterine device, and that this also has the greatest flexibility in terms of timing: it can be fitted up to 5 days after the earliest predicted date of ovulation, regardless of how many times unprotected intercourse has occurred.
     
  Talking about mifepristone, two recent studies have investigated the use of 600mg mifepristone as a single dose given within 72h of unprotected intercourse and in both to be very effective, so far no pregnancies occurred in the mifepristone group. WHO study shows that mifepristone dose can be lowered as much as 10mg without loss of efficacy and with the reduction of nausea.
     
  INJECTABLES
  Medroxyporgesterone acetate (Depo Provera or DMPA) in a dose of 150mg intramuscularly every 12 weeks is well established. Five large, controlled multicentre studies have been conducted, showing an in-use failure rate of 0.0-0.7 per 100 woman – years.
      
  Originally it was available in 3cc formulation and now it is available in 1cc formulation which causes much less discomfort.
     
  The probability of achieving amenorrhea is also a welcome side effects specially in patients with dysmenorrhea, menorrhagia and anemia and also there is improvement in symptoms of premenstrual syndrome.
     
  It also offers protection against pelvic inflammatory disease and there is hardly any increased incidence of ectopic. It has no appreciable effects on blood pressure or thrombosis risk. It is independent of intercourse and does not require a continuous motivation other than remembering to take a 3 monthly injection. It is also found to give relieve of focal migraine. 
      
  Though the method is reversible there is a median delay in return of fertility of 6 months. About the risk of breast cancer there is slightly increased risk in first 4 years of use, but, since this was greatest after the first injection and diminished rather than increased with duration of use, the observation is more likely to be due to some kind of bias, for example surveillance bias.
      
  The WHO study also showed no increase in risk for either cervical or ovarian cancers. In the case of endometrial cancer, there was a 5-fold protective effect. 
      
  Appropriate counselling, with the provision and discussion of information leaflets, is essential before the first injection as the greatest obstacle to the use of Depo Provera is undoubtedly adverse public perception.
     
  Combined oestrogen-progestogen injectables.
  Cyclofem, a combination of medroxyprogesterone acetate (25mg) and oestradiol cypionate (5mg) in a half cc dose, is a new injectbale contraceptive. WHO studies have shown first year failure rates of 0.2 per 100 woman years. It used to be given monthly and self injection appears to be a viable option.
    
  IMPLANTS
  Many of the problems associated with Implants were related to the insertion and removal of the six implants. Now a new, single rod implant, Implanon has been introduced in 1999. A significant advantage of Implanon is that it consists of a single, semi-rigid rod, measuring 40mm x 2mm, which is considerably easier both to insert and remove taking on an average, under 2 min and 3min. respectively. The rod is supplied in a sterile, disposable applicator and insertion does not require a skin incision. Removal, using a ‘pop-out’ technique, is facilitated by the rigidity of the capsule.
      
  The implant releases between 30-40 ug 3-ketodesogestrel (etonogestrel) per day and lasts for 3 years. The incidence of acne appears to be slightly lower than with the levonorgestrel implants. Amenorrhea is common in Implanon users than with Norplant. However, irregular bleeding can be a problem, as with all progestogen-only methods.
     
  The levonorgestrel-releasing intra-uterine system (Mirena)
  The Mirena consists essentially of a Nova T frame, within the stem of which is a steroid reservoir containing 52mg levonorgestrel, designed to release 20ug of hormone per 24h into the uterine cavity. Because of the reservoir, the stem is slightly wider than that of the Nova T, which may necessitate cervical dilatation in nulliparous women. Its efficacy is approximately 1.3 per 100 woman years and it is now licensed for 5 years. 
      
  Such is the profundity of the endometrial suppression by Mirena tha the device has been shown to be preferable to hysterectomy for the treatment of menorrhagia in a randomized trial and other studies showing reduction in blood loss of 97% after 12 months’ use. It is, therefore, a simple, fertility-conserving alternative to both hysterectomy and endometrial resection.
      
  There is no increase in the risk of pelvic infection and ectopic pregnancy but there is slight increase in the incidence of acne.
      
  In the next couple of years, it is hoped that the Mirena will be licensed for the treatment of menorrhagia, and also for use in hormone replacement therapy. This will give continuous source for progesteron and estrogen can be given by whatever route is preferred. Thus providing continuous combined therapy for women of all ages. It also can be used in the treatment or prevention of fibroids and also for patients who are on tamoxifen and those who suffer from premenstrual syndrome and are being treated with oestradiol by patches or implants.
      
  The life span of copper IUDs is becoming longer with the Copper T380 slimline now licensed for 10 years. Currently Nova T has 5-year license.
      
  The Gynefix
  The Gynefix is a novel, frameless IUD, which has been designed to try and overcome the problems of expulsion, heavy bleeding and increased dysmenorrhoea. It consists of six copper cylinders (5mm x 2.2 mm each) on a monofilament polypropylene thread. The upper and lower cylinders are crimped onto the thread to secure placement. At the upper end of the thread is a knot, which is implanted into the fundal myometrium, acting as an anchor.
      
  The device is licensed for 5 years, a failure rate of 0.5 per 100 woman-years and expulsion rates appear to be less than 1 per 100 woman-years. There are 2 more varieties postabortal and postpartum. The postabortal is called Gynefix PT and the postpartum is called Gynefix PP. The Gynefix PP has a slightly thicker polypropylene thread, and an injection moulded, cone shaped 4mm x 5mm biodegradable body immediately below the knot. This cone gradually biodegrades over 2-5 weeks and therefore, moulds to the involuting uterus.
      
  The Persona
  Natural Family Planning enters the age of technology. It is a micro-computer attached to a micro-laboratory. It is based on measurement of levels of luteinising hormone and oestrone-3-glucuronide (E3G) in early morning urine. The patient dips the test sticks in the urine and inserts in to the device and she is shown green light when the conception is unlikely and red light when conception is likely to occurs. With perfect use, failure rates are in the region of 6 per 100 woman-years.
      
  The device needs to be programmed for at least 3 months and the device is not suitable for women whose cycle lengths fall outside the range 23-35 days. The best use failure rate is still high compared to other methods and it should be used for spacing rather than preventing a pregnancy. 
      
  Barrier Methods:
  The arrival of the polyurethane condom is welcome. It is thinner, odour-free and is suitable for people who are sensitive to latex rubber.
      
  A female sterilisation is traditionally viewed as the final and most effective form of contraception. However, The US Collaborative Review of Sterilisation followed up over 10,000 sterilised women for nearly 15 years and showed that after 10 years, the cumulative failure rates of some techniques were much higher than expected. Another worrying finding was that one-third of the pregnancies were ectopic.
     
  Within the next year Cerazette, a desogestrel-containing progestogen-only pill (POP) is likely to become available. The dose is 75ug of desogestrel daily and it has been designed to inhibit ovulation in contrast to currently available POPs which act on cervical mucus. Thus there is a 12h pill taking safety margin rather than 3 h.
      
  The hormone delivery systems are becoming more varied, with both transdermal patches and vaginal rings. The ‘male pill’ may not be a figment of our imagination for much longer. Various combinations of androgen-only and androgen-progestogen combinations are under investigation. However, it is likely that the first versions will be injections or subcutaneous pellets.
      

• A Jefferson Penfield, (Department of Obstetrics and Gynaecology, Health Science Center,Syracuse).
  The Filshie clip for female sterilization : A review of world experience.
  Am J Obstet Gynecol, March 2000; 182: 485-9.
     
  In the past 20 years more than 3 million pairs of clips have been distributed worldwide. Ten year Canadian failure rates have not yet been published. Rioux and Yuzpe, who have used the Filshie clip for 15 years, reported an overall failure rate of 0.27% for interval procedures and 0.9% postpartum. In addition, Rioux et al reported no failure after a 7-year follow up of 497 patients. In Canada, at present the Filshie clip is used in 85% of female sterilisation procedures.
     
  Recommendations concerning Filshie clip application have been laid down by Filshie and should be adhered to. Long-term failure rates for Mark VI hinged Filshie Clip System sterilisation then as interval procedures are excellent.
  
  Long-term failure rates for Mark VI hinged Filshie Clip System sterilization (interval procedures)

                                                    Patients     Follow-up               Failures            Failure rate

  Investigator                                   (No.)              (y)                     (No.)                  (%) 

   

   
  Filshie                                              434            6 –15                  1                          0.23%.

  Heslip –                                            467              10                    1                         0.21%.

  Yuzpe –                                            497              10.                   0                         0

  Puraviappan –                                  796                7                     3                         0.4%.

  
  Table II

  Overall 10-year failure rates (interval procedures)

                                                   Patients                                    Failure rate

  Method                                      (No.)                                            (%)

  Bipolar coagulation                   2267                                         2.48

  Unipolar coagulation                 1432                                        0.75%;

  Yoon band application,             3329                                         1.77%,

  Hulka clip application,               1595                                         3.65%

  Interval partial salpingectomy      425                                          2.01%.

  
     

  
  Editor’s comment :The Filshie clip has proved to be highly acceptable because of ease of application, minimal tube destruction, maximum reversibility, and extremely low failure rates.
     

• Francisco Alvarez-Sanchez, Vivian Brache, et al (Biomedical Research Department, Santo Domingo, dominican republic and Campinas, Brazil)
  Prevalence of enlarged ovarian follicles among users of levonorgestrel subdermal contraceptive implants (Norplant)
  Am J Obstet Gynecol, March 2000, 182: 535-9
     
  Objective : The aim of this study was to determine the prevalence of enlarged follicles, as detected by a single clinical or ultrasonographic examination, among users of levonorgestrel subdermal contraceptive implants (Norplant implants).
     
  Study Design: This was a cross-sectional study of 103 users of Norplant implants and 50 users of the Tcu380A intrauterine contraceptive device. Enlarged follicles (>25mm) were followed up weekly).
        
  Enlarged follicles were detected by ultrasonography in 17.5% of Norplant implants users and 4% of Tcu380A intrauterine contraceptive device users. There was no difference according to duration of use. The longest time to involution of the follicles was 4 weeks. Forty percent of the enlarged follicles detected by ultrasonography were also detected by bimanual pelvic examination.
         
  Conclusion: Enlarged follicles are a frequent finding among women who use Norplant implants, but they are less frequent than described in previous studies,, which were based on serial ultrasonographic scans in selected groups of users. Physicians and users should be aware of the transient nature of these enlarged follicles, which do not require intervention.
       

• Trends in Contraceptive Use in the United States: 1982-1995
  LJ Piccinino, et al (Natl Ctr for heatlh Statistics, Hyattsville, Md)
  Fam Plann Perspect 30:4-10 &46, 1998.
      
  Editorial comments: Nationwide surveys of contraceptive use in the United States are performed periodically with the planning and funding of US government agencies. Surveys were performed in1982, 88, and 95, and this study summarizes the changes that have occurred with contraceptive use during these years. Between 1982 and 1995, the use of contraceptives by women of reproductive age increased so that, in 1995, only about 5% of women who were sexually active and not wishing to conceive were using no method of contraception. Sterilization is the most common method of pregnancy prevention in the United States followed by use of oral contraceptives and the male condom. Use of the condom has increased markedly in the United States during this period. Relatively few women use each of 3 very effective methods, the IUD, progestin injections, and progestin implants. Less than 1 million women used each of these methods in 1995.
        

• Jeanet M Kemmeren, Ale Algra, Diederick E Grobbee
  Third Generation Oral Contraceptives and Risk of Venous Thrombosis: Meta-Analysis 
  BMJ Vol. 7305, 21 July 2001; Pg. 131-4
       
  The newer third generation oral contraceptives contained desogestrel or gestodene. The second generation oral contraceptives contained levonorgestrel.
        
  An extensive meta-analysis comparing the third generation with the second generation oral contraceptives showed that the third generation oral contraceptives are associated with increased risk of venous thrombosis
         

• E. Mandelin, H. Koistinen, et al (Helsinki University Central Hospital and University of Helsinki, Helsinki, Finland, et al)
  Endometrial Expression of Glycodelin in Women with Levonorgestrel-Releasing Subdermal Implants
  Fertil Steril, September 2001; Vol. 76(3): 474-8
          
  Objective : To determine whether subdermal levonorgestrel implants induce endometrial expression of glycodelin.
            
  Design : Cross-sectional, blinded study.
          
  Setting : University clinic.
          
  Patient(s) : One hundred and eight women with subdermal implants and 19 postmenopausal women.
          
  Intervention(s) : Endometrial biopsies, curettages, and hysterectomies.
           
  Main Outcome Measure(s) : Endometrial glycodelin expression was examined through immunohistochemistry, in situ hybridization and morphologic endometrial dating.
          
  Result(s) : Overall, 80% of the endometrial specimens obtained from women with subdermal levonorgestrel implants stained positive for glycodelin. Endometrial morphology of these women showed proliferative (71%), inactive/weakly proliferative (19%), menstrual or regenerating (6.5%), and other patterns (2.8%). 
         
  Of these, 79%, 71%, 100% and 100% were glycodelin positive, respectively. Nineteen specimens were obtained during the mid-cycle when glycodelin is not normally expressed: of these, 89% stained positive for glycodelin. 
          
  Implant-related amenorrhea was associated with endometrial glycodelin expression in 58% of the women, whereas the endometrium specimens obtained from women with postmenopausal hypoestrogenic amenorrhea contained no detectable glycodelin.
          
  Conclusion(s) : Subdermal levonorgestrel implant use is often associated with endometrial expression of glycodelin. Because glycodelin has been shown to inhibit sperm-egg binding, the induction of glycodelin may contribute to the contraceptive activity of the implant.
           

• Alfred Poindexter, (Baylor College of Medicine, Houston, Texas)
  The emerging use of the 20-mg oral contraceptive.
  Fert.& Ster., vol.75(3), March 2001, pg.457-65
    
  Objective: To highlight studies that investigated the efficacy , safety, and tolerability of low-dose oral contraceptives (OCs) containing 20 mg of ethinyl estradiol (EE) and to discuss the use of these low-dose contraceptives in women from adolescence to menopause and the noncontraceptive health benefits likely to be afforded by low-dose contraceptives.
   
  Design: Relevant literature was identified by searching MEDLINE and EMBASE. Other sources were located by consulting the bibliographies of the material collected from Medline and EMBASE. Sources for additional information included documents from the United States Food and Drug Administration and the Physician’s Desk Reference (54th ed.)
    
  Prevention of Gynecologic and Other Cancers.
  The protective effect of OCs against ovarian cancer is one of the most well-established noncontraceptive health benefits of OCs. OCs are consistently connected with substantial declines in ovarian cancer, a protective benefit that increases significantly with the duration of OC use and continues for as long as 15-20 years after discontinuation of OCs. A recent report demonstrates that Ocs also protect against hereditary ovarian cancer, such as in women with BRCA1 and BRCA2 gene mutations who have a higher lifetime risk of ovarian cancer.
    
  Use of OCs also reduces the risk of developing endometrial cancer. This protective effect is greatest for nulliparous women and women with low parity, whose risk for endometrial cancer is highest. More importantly, this protection persists for 15-20 years after discontinuation of OC use.
   
  A world-wide epidemiological study conducted at Oxford University that reanalyzed 54 studies in 25 countries reported a small increase in the relative risk of having breast cancer diagnosed in current users of OCs. When several cohort and case-control studies were reviewed, a favorable effect of OCs on the risk of colorectal cancer, a nongynecologic cancer, was demonstrated. How 20-mg OCs affect these gynecologic and nongynecologic cancers is unknown and warrants further study.
   
  Prevention of Benign Gynecologic Conditions
  An inverse association has also been demonstrated between OC use and risk of all types of benign breast disease but has been especially apparent for proliferative types of the disease.
   
  A progressive decline in the incidence of ovarian cysts has been associated with ovarian suppression.
   
  Improvement of Menstrual Irregularities.
  OCs decrease menstrual flow, shorten the duration of bleeding, treat dysfunctional bleeding, and reduce the incidence of iron deficiency anemia. In addition, OCs effectively treat dysmenorrhoea, which affects more than 50% of menstruating women, presumably by reducing prostaglandin production and thinning the endometrial lining. OCs are also commonly used to treat endometriosis.
    
  Acne
  Combination OCs are antiandrogenic in that they can suppress ovarian, adrenal, and peripheral production of androgens and decrease the amount of bioavailable testosterone by increasing levels of sex hormone binding globulin (SHBG) in randomized studies. In addition, when the effect of four different Ocs on androgens was compared, the one 20-mg EE pill tested was as effective as the other OCs containing 30-35-mg of EE in reducing androgens and increasing SHBG.
   
  Osteoporosis.
  Although low-dose 20-mg OCs were not investigated in these studies, it is likely that 20-mg OCs will also enhance bone density as evidenced by a significant increase in bone mineral density in postmenopausal women with a hormone replacement regimen containing 10mg of EE.
   
  Summary:
  The current lowest available dose of EE used for OCs in the United States is 20 ug. Formulations with 20 mg of EE are both efficacious and acceptable and at the same time reduce the incidence of estrogen-related side effects to a minimum. Many of the noncontraceptive health benefits of OCs result from the suppression of ovulation and are thus likely to occur with 20-mg OCs, because this lowest effective OC dose inhibits ovarian activity. OC provides both contraceptive and noncontraceptive health benefits to most women, from adolescence to menopause, without complications.