Cost-benefit analysis of enhancing the uptake of long-acting reversible contraception in Australia.

Objective Long-acting reversible contraception (LARC) is the most effective form of reversible contraception, but its use in Australia is low compared with other countries. The aim of this study was to evaluate the economic effect of an increase in LARC uptake to international rates. Methods An economic model was designed to assess two scenarios, namely increasing the current rate of LARC uptake of 12.5% to the international benchmark of 14.8% among: (1) women currently using the oral contraceptive pill (OCP); and (2) women at risk of pregnancy and not using contraception. Model inputs included cost of contraceptive methods, discontinuation rates and abortion and miscarriage costs associated with unintended pregnancies. Results Women who switch from an OCP to LARC would save A$114-157 per year. Those not currently using any contraception who adopt LARC would incur costs of A$36-194 per year, but would reap savings from the reduction in unintended pregnancies. Over 5 years there would be a net saving of A$74.4 million for Scenario 1 and A$2.4 million for Scenario 2. Conclusion Greater use of LARC would result in a net gain in economic benefits to Australia. These benefits are largely driven by women switching from an OCP to LARC who have reduced costs, as well as women wishing to avoid pregnancy who choose to use LARC rather than no method. This evidence will support women making an informed contraceptive choice and policy makers in increasing the accessibility of LARC. What is known about the topic? LARC is the most effective form of reversible contraception, but uptake in Australia is relatively low. What does this paper add? There are economic benefits to society for women who switch from an OCP to LARC, as well as for women who switch from no contraception to LARC. What are the implications for practitioners? The findings of this study will support women in making an informed contraceptive choice and policy makers in increasing the accessibility of LARC.

Continuation of postmenopausal hormone replacement therapy: comparison of cyclic versus continuous combined schedules.

Discontinuation of hormone replacement therapy (HRT) is much more common than what is reported in randomized, double-blind clinical trials. Our purpose in this retrospective study, using a prescription database, was to compare the continuation rate among women who took cyclic combination therapy adding progesterone to estrogen (CYC-PERT) or continuous combined estrogen progestin therapy (CC-PERT). The study subjects were 1,532 women, ≥45 years old, who initially filled index prescriptions for 0.625 mg conjugated estrogens. They were divided into two groups (CYC-PERT = 644, CC-PERT = 888) on the basis of coprescribed medroxyprogesterone. We found that for all women initiating therapy, 35-40% did not return for a refill and 76-81% stopped therapy within 3 years. Those prescribed CC-PERT initially were more likely to stop than those prescribed CYC-PERT (rate ratio [RR] = 1.20; 95% confidence interval [CI] = 1.06-1.35). Adjustments for age, year of starting medication, cost of medication, and prescriber specialty did not affect the difference in discontinuation between the two regimens (RR 1.18, 95% CI = 1.04-1.34). We conclude that the likelihood of women continuing HRT beyond 3 years of initiation is low. Furthermore, compared with CYC-PERT users, those receiving CC-PERT have a slightly higher probability of discontinuation. Efforts should be made to understand why three quarters of women beginning HRT will stop it long before it can provide major long-term benefit.

CBP 1011: Colirest, Hematrol.

InKine Pharmaceutical Co. is developing an oral compound, CBP 1011, for the treatment of immune thrombocytopenic purpura (ITP) [Hematrol] and for the treatment of inflammatory bowel disorders, ulcerative colitis and Crohn's disease (Colirest). This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. CBP 1011 or medroxyprogesterone, is a progesterone agonist and inhibits pro-inflammatory mediators such as interleukin-6 and tumour necrosis factor (TNF). CBP 1011 was originally developed by CorBec Pharmaceuticals, which in 1997 was aquired by Panax and then intergrated into InKine Pharmaceuticals. According to a company spokesperson, InKline is pursuing outlicensing opportunities for Hematrol since the company's current commercial focus is on gastrointestinal products. In June 2000, InKine announced the completion of a study comparing the bioavailability of a commercially viable tablet formulation of CBP 1011 to the original capsule formulation that is currently being used in the company's phase III studies in patients with idiopathic thrombocytopenic purpura. Preliminary results from this study indicate that the bioavailability of the tablet formulation does not differ significantly from that of the capsule formulation. The trial enrolled ITP patients (i) who are HIV positive, (ii) who are chronic ITP sufferers despite having had a splenectomy, (iii) who are older, or (iv) who have less severe thrombocytopenia. In preclinical trials, CBP 1011 was shown to decrease lymphocyte infiltration into the bowel compared with the control. Studies also show that it possibly offers safety benefits over steroid therapies. In June 2001, InKine commenced enrolment for a pivotal phase III trial in the treatment of Crohn's disease. This randomised, double-blind trial will enrol approximately 250 patients and will compare two doses of CBP 1011 (400 and 1000mg) with placebo. In April 2003, the US Patent and Trademark Office granted InKine Pharmaceutical a 'Notice of Allowance' for the 'Method of Treating Inflammatory Conditions with Progesterone or Progesterone Analogs'. This patent for medroxyprogesterone (Colirest) provides InKine patent protection for the use of Colirest in treating patients with Crohn's disease, ulcerative colitis, proctitis, microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, drug-induced oesophagitis, coeliac disease, recurrent polyps and haemorrhoids. The patent protection also covers Colirest in a variety of delivery forms such as tablet, enema, suppository, foam, gel, ointment and suspension.

Near-infrared spectroscopy in the assessment of cerebral oxygenation at high altitude.

Hypoxia plays a key role in the pathogenesis of acute mountain sickness (AMS), but individual susceptibility is variable and cerebral symptoms do not always correlate with PaO2 measurements. Cerebral hypoxia may be more relevant than PaO2. We studied trends in cerebral regional oxygen saturation by the technique of near-infrared spectroscopy in 20 subjects ascending rapidly to 4680 m. Subjects were enrolled in a placebo-controlled, double-blind trial of medroxyprogesterone for the prevention of AMS. The fall in cerebral oxygen saturation was less than in the periphery. At 4680 m, cerebral oxygenation correlated with peripheral saturation but not with PaCO2 or with cerebral symptoms scores. At 4680 m, subjects on medroxyprogesterone had higher cerebral and peripheral saturation compared with those on a placebo. We conclude that cerebral oxygenation monitored with the Critikon 2020 system provided important information on the complex relationship of hypoxia to AMS and that other factors, such as changes in blood flow or capillary permeability, may be equally important.

Sequential estrogen and progestogen therapy: assessment of progestational effects on the postmenopausal endometrium.

Healthy postmenopausal women were randomly assigned to groups receiving 28-day treatment cycles of estradiol (E2) valerate (2 mg, days 1-21) combined with medroxyprogesterone acetate (10 mg, days 12-21) (N = 18), 17 beta-estradiol (1.5 mg, days 1-24) combined with desogestrel (150 micrograms, days 13-24) (N = 20), or placebo (N = 18). The progestational effects on the endometrium were assessed by histology, uterine bleeding pattern, and biochemical markers of secretion measured in endometrial tissue (E2 and isocitrate dehydrogenase) and serum (placental protein 14). After 2 years of therapy, 24 women in the hormone groups had secretory endometrium and 13 had atrophic endometrium; in the placebo group, the results were one and 15, respectively. Withdrawal bleeding generally started between days 9-12 after the addition of progestogen in the E2-medroxyprogesterone acetate group, and between days 14-17 in the E2-desogestrel group. All three biochemical markers of secretion were increased in each of the hormone-treated groups compared with the placebo group (P less than .01-.001). Serum placental protein 14 was twice as high in the secretory as in the atrophic phase (P less than .01). Isocitrate dehydrogenase, but not E2 dehydrogenase, was also higher in the secretory phase (P less than .05). Only serum placental protein 14 was significantly related to the uterine bleeding pattern (P less than .01). We conclude that serum placental protein 14 reflects both endometrial histology and bleeding pattern and may be a useful marker of progestational effects on the endometrium. The markers of secretion measured in endometrial tissue are not as reliable for endometrial histology or bleeding pattern.

State also pays for Depo-Provera.

PIP: A mail survey of 50 U.S. states revealed that of 32 who responded, 15 will pay for Depo-Provera under the Medicaid program, for contraception. Another 2 pay for contraceptive visits, which may include any type of contraceptive. As of May 1991, no state now requires prior approval in writing to use Depo-Provera as a contraceptive. Contraception is an unlabeled indication for Depo-Provera, but it is legally acceptable to use the drug for an unlabeled indication. PHP and Blue Shield have reimbursed users for Depo-Provera prescriptions in Minnesota. Minnesota's Medicaid (Medical Assistance) has paid for Depo-Provera since July 1990. The author added that she has never seen a failure of this method in 30 years of use when given correctly, that is 150 mg every 90 days.^ieng

Depo Provera: a profile of current users.

This retrospective study reviewed the current users of Depo-Medroxy-Progesterone-Acetate (Depo-Provera) from April to June, 1987, within the Family Planning Association of Victoria's Richmond Clinic. The profile that emerged from the study showed the clients were of average intelligence, well informed, had tried other methods of contraception, had a high number of unplanned pregnancies and chose to use Depo-Provera as other methods of contraception were unsuitable.

PIP: In a retrospective study the case histories of 70 users of Depo-Provera (containing depo medroxyprogesterone acetate) were reviewed during April-June 1987 at the Family Planning Association of Victoria's Richmond Clinic in Australia to ascertain their socioeconomic status, obstetric and contraceptive history, and side effects of Depo-Provera use. 47 (67%) were employed; 20 (29%) were health care card holders (8 were unemployed and 6 were supporting mothers); 2 were wards of state referred from adolescent institutions; and 3 women (4%) had intellectual disability. 37 (53%) had been pregnant with the total number of pregnancies of 65; 16 women had a total of 25 terminations of pregnancy; and 1 woman had a history of 4 therapeutic abortions. 53 women (76%) had started using contraception before the age of 20; 47% had used more than 1 type of contraception, 46% had used oral contraceptives only, 23% had used the condom, and 5% had used nothing. Age range at start of Depo Provera use was 14-40 years. The reasons given for commencing Depo-Provera included a combination of problems with other methods, forgetting OCs, and side effects of OCs. 47 (67%) had requested the use of Depo-Provera, of whom 13 (18%) had used it previously. 43 (61%) used Depo-Provera for 1 year or less, and only 1 patient had used it for 6 years. Among 52 women (74%) who had more than 1 dose of the injectable, the major side effects related to menstrual disturbances; 31 (41%) had amenorrhea. 2 of these women had breakthrough bleeding during the 1st dose. 17 women (24%) had either irregular bleeding or breakthrough bleeding, while 1 patient continued to have regular periods. 7 women (10%) had other side effects including depression; 4 women (6%) complained of weight gain; and 2 (3%) had breast soreness. 41 women (59%) were smokers, and 40% of them smoked 15 or more cigarettes per day. 35% of the women continued with the method beyond the study period, while the proportion of women within the clinic who continued using Depo-Provera was about 0.5%.

[Doctors and injectable contraception. Analysis of the logistics of prescribing in accordance with the views expressed by doctors]. / Médecins et contraception injectable. Analyse des logiques de prescription à partir des discours de médecins.

Injectable contraception (IC) using medroxyprogesterone acetate (Depoprovera) and norethisterone enanthate (Noristerat) has been discussed in numbers of publications since the Food and Drug Administration (FDA) of the USA have refused to authorize the use of Depoprovera as a contraceptive in America. This has provoked a large number of publications in the international literature. The refusal was based on the potential oncogenic risk of the molecule. The distribution of this product as a contraceptive in developing countries and its restricted authorisation in many industrialised countries including France has brought about contradictory debates about the assessment of this method (secondary effects, risks of developing cancer and teratogenesis). In 1986 we started a research using close collaboration between the health teams of Seine-Saint-Denis (which control clinics, family planning clinics and hospitals) in order to try to find some solution to this problem "for or against IC". The object of this research was to find out how acceptable this method was as compared with other contraceptive methods. The fact that many disciplines were involved (gynaecologists, sociologists, epidemiologists and pharmacologists) in this work made it possible first to find out the conditions under which IC was prescribed (by sociological analysis and discussions with doctors). And the socio-cultural features in which the doctors who prescribed this method of contraception were situated also came into play. The criteria under which ICs are prescribed are not mainly medical but are narrowly linked to socio-cultural factors and the socio-economic factors of the women for whom it is prescribed: and this is in comparison with other methods of contraception. Prescribing this substance has a degree of urgency about it.