Contraceptivos injetáveis acetato de medroxiprogesterona + cipionato de estradiol (25mg + 5mg) e algestona acetofenida + enantato de estradiol (150 mg + 10mg) para mulheres em idade fértil / Injectable contraceptives medroxyprogesterone acetate + estradiol cypionate (25mg + 5mg) and algestone acetophenide + estradiol enanthate (150mg + 10mg) for women of childbearing age

INTRODUÇÃO: Estima-se que metade das gestações ocorram sem planejamento, em todo o mundo. Como consequência, aumenta também a chance de aborto, com incremento estimado de 51 para 61 por 1.000 mulheres entre 1990-1994 e 2015-2019. A contracepção com métodos modernos é considerada uma estratégia custo-efetiva e fundamental para alinhamento entre a possível vontade de ter filhos e outros determinantes que impactam na escolha das pessoas envolvidas. Os métodos contraceptivos podem ser classificados em tradicionais ou modernos, de curta ou de longa duração, sendo considerados, de forma geral, como métodos tradicionais a abstinência sexual e os comportamentais. Os métodos modernos de ação curta são os orais, injetáveis, preservativos e diafragmas; e os métodos modernos de ação prolongada, DIU e implantes. Os anticoncepcionais injetáveis, quando combinados, contêm além do progestogênio sintético, um éster de estrogênio natural ­ o estradiol, diferentemente dos estrogênios sintéticos presentes nos anticoncepcionais orais. A posologia desses anticoncepcionais pode ser mensal, bimestral ou trimestral dependendo da sua composição e em relação aos orais po

Comparison of two regimens of a monthly injectable contraceptive containing dihydroxyprogesterone acetophenide and estradiol enanthate.

INTRODUCTION: This study compared two regimens of a monthly injectable contraceptive containing dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (Perlutan) over 12 cycles of use. METHODS: Three hundred sixty-five adolescents were randomized into two groups. The patients in Group 1 received an initial injection of Perlutan on the 1st-5th day of their menstrual cycle and subsequent injections every 30 +/- 3 days, whereas those in Group 2 followed the traditional schedule of administration in which the first injection is administered between Days 7 and 10 of their menstrual cycle and subsequent injections 7-10 days after Day 1 of withdrawal bleeding. This schedule may result in an irregularity in the timing of injections. RESULTS: No significant difference was found between the two groups regarding tolerability or pregnancy (two in Group 1 and three in Group 2). CONCLUSION: Monthly administration limits the annual number of injections to a maximum of 12, thus frequently reducing the total annual dose while maintaining efficacy and tolerability similar to those obtained with the traditional regimen.

Efficacy, acceptability, and clinical effects of a low-dose injectable contraceptive combination of dihydroxyprogesterone acetophenide and estradiol enanthate.

A total of 1,904 women, aged 15-38, used an injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate, given once during each menstrual cycle between the 7th and 10th day, and preferably on the 8th day of the cycle, for a total of 17,576 cycles. Of these 1,904 women, 1,197 completed 12 cycles of use of the injectable combination. One subject became pregnant during the trial, resulting in a cumulative pregnancy rate of 0.07%. Principal reasons for discontinuation were personal, non-medical reasons, such as lost to follow-up, no longer wished to continue, protocol violation, desire to change to another contraceptive method, moved away, or other personal reasons. Mean weight of 1,901 subjects at admission to the trial was 53.5 +/- 0.2 kg and this increased to 54.3 +/- 0.3 kg after 12 cycles of use. Approximately 50% of subjects experienced menstrual bleeding similar to normal throughout the study period. The most frequent menstrual abnormality was irregular bleeding, experienced by approximately one-third of subjects.

Vaginal bleeding patterns in users of Perlutal, a once-a-month injectable contraceptive consisting of 10 mg estradiol enanthate combined with 150 mg dihydroxyprogesterone acetophenide. A trial of 5462 woman-months.

Perlutal (other names: Topasel, Perlutan) is a once-a-month injectable contraceptive that contains 10 mg estradiol enanthate and 150 mg dihydroxyprogesterone acetophenide. A prospective trial was conducted in 216 women in Medellín, Colombia, over five years (5,462 woman-months) to establish the rates of the different vaginal bleeding patterns during the use of Perlutal, and to assess their relation with discontinuation of the Perlutal regimen. It was found that with the use of Perlutal, the duration of menstrual bleeding decreased from 3.9 to 2.7 days (p < 0.01), and that the incidence of dysmenorrhea decreased from 31% to 1.6% (p < 0.01). At one year of follow-up, the incidence of altered bleeding patterns was 5.1%. The discontinuation rate due to an altered bleeding pattern was 3.9%. It is concluded that the low incidence of altered bleeding patterns observed with the use of Perlutal leads to a low discontinuation rate among users.

Níveis séricos de HDL-C, LDL-C e correlaçäo LDL/HDL (índice de Castelli II) em adolescentes usuárias de contraceptivo injetável mensal / HDL-C, LDL-C Serum levels and the relation LDL/HDL (Castelli's II Index) in adolescents using monthly injectable contraceptive

OBJETIVO: Avaliar as possíveis alteraçöes no metabolismo lipoprotéico em adolescentes usuárias de contraceptivo injetável mensal após 12 ciclos de tratamento. PACIENTES E MÉTODOS: Foram avaliados os níveis séricos de lipoproteínas, em 30 adolescentes usuárias da associaçäo Acetofenido de Dihidroxiprogesterona 150mg e Enantato de Estradiol 10mg, por um período de 12 ciclos. Como grupo controle foram estudadas 31 adolescentes com as mesmas características, usuárias de dispositivo intra-uterino modelo T Cu200. foram tomadas amostras sangüíneas antes do início do tratamento em ambos os grupos e aos 60, 180 e 360 dias após iniciado o uso da medicaçäo ou do dispositivo intra-uterino e nestas ocasiöes dosadas as fraçöes HDL-C, LDL-C e calculada a relaçäo LDL/HDL. Os grupos estudados eram homogêneos em suas características físicas e também nos parâmetros lipoprotéicos pré-tratamento. RESULTADOS: Após 12 ciclos näo foram encontradas diferenças significativas nos parâmetros estudados, em ambos os grupos. As alteraçöes encontradas ao final do estudo foram semelhantes em ambos os grupos e devidas às características próprias do grupo estudado. CONCLUSÄo: Podemos concluir que o contraceptivo hormonal injetável mensal composto de 150mg de Acetofenido de Dihidroxiprogesterona e 10mg de Enantato de Estradiol se comporta como um contraceptivo näo hormonal no que concerne ao metabolismo de lipoproteínas, näo provocando alteraçöes significativas neste metabolismo.

Multicenter, double-blind, comparative clinical study on the efficacy and acceptability of a monthly injectable contraceptive combination of 150 mg dihydroxyprogesterone acetophenide and 10 mg estradiol enanthate compared to a monthly injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide and 6 mg estradiol enanthate.

Healthy, regularly menstruating women, aged 14-38 years, were enrolled in a comparative, double-blind, phase III, clinical trial to evaluate the contraceptive efficacy and acceptability of a combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate compared to the commercially available contraceptive combination of 150 mg dihydroxyprogesterone acetophenide with 10 mg estradiol enanthate. Subjects received the contraceptive combination intramuscularly, between the 7th and 10th day of each menstrual cycle, during 12 consecutive menstrual cycles. Approximately 60% of the subjects in both groups completed the study. Principal reasons for discontinuation were personal, nonmedical reasons. Principal medical reasons for discontinuation were menstrual-related, irregular bleeding being the most frequent. Differences in menstrual patterns between the two groups did not lead to differences in discontinuation rates. Three contraceptive failures occurred during the trial, one in Group A (90/6 mg) and two in Group B (150/10 mg), indicating that the lower dose formulation is at least as efficient as the higher dose.

Dihydroxyprogesterone acetophenide 150 mg + estradiol enantate 10 mg as monthly injectable contraceptives.

A survey among users and health personnel participating in the Salvadorian Social Security Institute (ISSS) Family Planning Program revealed interest in including a monthly preparation for injection as a contraceptive method offered by this Institution. The formulation containing dihydroxyprogesterone acetophenide (DHPA) 150 mg + estradiol enantate (E2EN) 10 mg was chosen for conducting an open and prospective study of efficacy and tolerability. Between January 1992 and March 1994, 7054 women were treated with this product for a total of 60010 months. A sample composed of 4505 women treated at this Institution confirmed that average users are young, have one or two children, do not show a particular geographical distribution and choose the monthly injection instead of oral contraceptives as the first contraceptive method or for the puerperium. The study formulation showed a high efficacy (Pearl Index: 0.018) and tolerability (general withdrawal rate throughout the study: 27.09%). The most frequent adverse events included bleeding disorders, headache and mastalgia; their incidence decreased spontaneously from the sixth month (3.9%), reaching 0% after two years. Treatment was discontinued due to adverse events in 3.47% of women. No significant bodyweight or systolic and diastolic blood pressure alterations were observed. Based on these results, the monthly injectable contraceptive was included in the basic product list at ISSS.

Metabolic effects of once-a-month combined injectable contraceptives. The World Health Organization Task Force on Long-Acting Systemic Agents for Fertility Regulation, Geneva, Switzerland.

The results of metabolic studies on once-a-month combined injectable contraceptives are summarized, focusing on four preparations: dihydroxyprogesterone acetophenide 150 mg/estradiol enanthate 10 mg; depot-medroxyprogesterone acetate 25 mg/estradiol cypionate 5 mg; norethisterone enanthate 50 mg/estradiol valerate 5 mg; and 17 beta-hydroxyprogesterone caproate 250 mg/estradiol valerate 5 mg. Their effects on carbohydrate metabolism, lipid metabolism, hemostasis, serum prolactin, cortisol, binding globulins and liver functions are reviewed. Areas requiring further research are identified.

Pharmacodynamic effects of once-a-month combined injectable contraceptives.

The pharmacology and clinical assessment of existing first generation once-a-month combined injectable contraceptives, mainly Deladroxate and Chinese Injectable No. 1, are reviewed. Although these two types of monthly injectables have been used in some million women in China and Latin America, Deladroxate needs indepth re-evaluation of its long-term toxicity and possible accumulation. For injectable No. 1, its disadvantage of being administered on an erratic schedule will cause significant confusion in family planning practice. When used in a strict once-a-month schedule, it is not sufficiently effective for contraception. In order to attain predictable menstrual cycle control as well as high efficacy with a 30-day injection schedule, two improved once-a-month injectable formulations, Cyclofem and Mesigyna, were developed. Pharmacokinetic/pharmacodynamic study on estrogenic components suggested that estradiol valerate and cypionate were suitable estrogen esters to give elevated plasma estrogen levels for 7 to 11 days. After a single injection of Cyclofem and Mesigyna, both formulations showed equal contraceptive effect with inhibition of follicle maturation for some 30 days and ovulation, corpus luteum formation for some 60 days. Multicentre studies on the optimization of dosages of progestogens and estrogens in once-a-month injectables confirmed that the full doses of Cyclofem (DMPA 25 mg/estradiol cypionate 5 mg) and Mesigyna (NET-EN 50 mg/estradiol valerate 5 mg) are suitable for large scale clinical trials. Pharmacodynamics and progestogen/estrogen ratio study indicated the importance of not only the absolute amounts of the progestogen and estrogen but also of their ratio. Reduction of estrogen dose resulted in breakthrough ovulation with both Cyclofem and Mesigyna. Also, it is important to note that the second part of the injection cycle is dominated by the progestogen component of both monthly formulations. A longitudinal study indicated that there is no accumulation of norethisterone after 12 months of treatment with NET-EN 50 mg and estradiol valerate 5 mg.

PIP: About 1 million women in Latin America and China have used the 1st generation once-a-month combined injectable contraceptives Deladroxate and Chinese Injectable No. 1. Animal toxicity studies of Deladroxate found pituitary hyperplasia in rats, breast tumors in beagles, and accumulation of estradiol enanthate in the body. Thus, long-term toxicity and accumulation of Deladroxate need to be reevaluated. The erratic schedule of the Injectable No. 1 (initially administered on day 5 with 2 ampoules or 1 dose on day 5 and 1 dose on day 12; subsequent administration on the 10-12th day of the cycles) will confuse acceptors and family planning providers. Yet, a strict once-a-month cycle of Injectable No. 1 does not adequately protect against conception. Researchers have developed 2 improved once-a-month injectable formulations, Cyclofem and Mesigyna, to achieve good menstrual cycle control and high efficacy. The estrogen components of both formulations (estradiol valerate and cypionate) sufficiently elevate plasma estrogen levels for 7-11 days. One injection of both formulations inhibits follicle maturation for about 30 days and ovulation and corpus luteum formation for about 60 days. The doses of Cyclofem (25 mg depot-medroxyprogesterone acetate + 5 mg estradiol cypionate) and Mesigyna (50 mg norethindrone acetate + estradiol valerate) have been found to be optimal for use in large scale clinical trials. Not only are the absolute amounts of the progestogen and estrogen important, but also the progestogen/estrogen ratio. A lower estrogen dose in both Cyclofem and Mesigyna effects breakthrough ovulation. The progestogen component predominates the 2nd part of the injection cycle in both formulations. Norethindrone does not accumulate in the body after 12 months of treatment with Mesigyna.

Once-a-month injectable contraceptives: efficacy and reasons for discontinuation.

Reports of the phase III clinical trials on four combined progestogen-estrogen once-a-month injectable contraceptives, Deladroxate, Cyclofem, Mesigyna and Chinese Injectable No. 1, are reviewed focussing on efficacy and reasons for discontinuation. Deladroxate, currently used in many Latin American countries has proved to be highly effective and well accepted. However, this combination was withdrawn by the original manufacturer because the progestogen component of this drug induced a high number of breast cancers in dogs and very curious pituitary hyperplasia in rats. Cyclofem and Mesigyna were found to be highly effective and highly acceptable drugs. Side-effects were minimal and were of minor importance. The Chinese Injectable No. 1 had unacceptably high failure rates with a monthly injection schedule. After doubling the dose in the first month of use, the efficacy was satisfactory. It was found that all monthly injectable contraceptives provided better cycle control than the every 3 months depot-medroxyprogesterone acetate, although abnormal bleeding was still the main drug-related complaint and reason for discontinuation. Missed appointment is another reason for discontinuation which might reflect the problem of frequent injection schedule, thus indicating the need for proper selection of the users and good counselling.

PIP: This literature review examines the efficacy and reasons for discontinuation of 4 combined progestogen-estrogen, once-a-month injectable contraceptives: Deladroxate, Cyclofem, Mesigyna, and Chinese injectable No. 1. Deladroxate is used mainly in Latin America, while the Chinese injectable No. 1 is largely limited to China. Among 18 studies, no pregnancies occurred in the 3017 women using Deladroxate (32,857 woman-months). It was well accepted, but the manufacturer withdrew it from the market after studies showed that the progestogen (dihydroxyprogesterone acetophenide) caused dogs to develop breast cancer and rats to develop an odd pituitary hyperplasia. Of the 4 once-a-month injectables, Cyclofem and Mesigyna provide the most promise. They are very effective at preventing pregnancy (0-0.23/100 women-years of use and 0.08-0.48/100 women-years of use, respectively). Acceptance of Cyclofem and Mesigyna was high. Side effects were limited and had minimal importance. An advantage of Cyclofem and Mesigyna is their much better cycle control than the once-every-3 months injectable Depo-Provera. The failure rate of the Chinese Injectable No. 1 on the once-a-month injection schedule was too high (10.35/100 women-years of use). When researchers doubled the dose in the 1st month of use, however, efficacy was satisfactory (0.8/100 women-years of use). The main drug-related complaint and reason for discontinuation of all once-a-month injectables was abnormal bleeding. Another key reason for discontinuation was missed appointment, suggesting that a frequent injection schedule poses a problem. Good planning and health workers properly selecting users and providing them good counseling may overcome this problem. Frequent visits would increase the staff work load.

Evaluación de la potencia hormonal del anticonceptivo inyectable mensual de dihidroxiprogesterona acetofenico 150 mg y estradiol enantato 10 mg, comparativamente con tratamientos anticonceptivos orales

Se realizó un estudio retrospectivo, comparativo, abierto en 58 mujeres voluntarias del Centro de Planificación Familiar, PROFAMILIA, de Santafé de Bogotá, Colombia. La potencia hormonal del anticonceptivo inyectable mensual constituido por Dihidrixiprogesterona Acetofénido (DHPA), 150 mg y Estradiol Enantato (EEn), 10 mg, fue comparada con la de otros anticonceptivos de uso habitual (píldoras de Etinilestradiol (EE), 0.050 mg y Levonorgestrel (LNG), 0.250 mg; EE, 0.030 mg, LNG, 0.150 mg y métodos no hormonales), mediante la determinación de triglicéridos, HDL/DL colesterol, cobre, ceruloplastia, cortisol total y libre, CBG, testosterona total y libre y SHBG en el suero de usuarias crónicas. Las usuarias de métodos no hormonales fueron el grupo de control. En los exámenes de laboratorio, los niveles de triglicéridos fueron más altos y los de testosterona total y libre más bajos en las mujeres que emplean DHPA 150 mg + EEn 10 mg y en las que utilizan píldoras. Tales modificaciones fueron levemente menores en el grupo que emplea el inyectable. Los efectos de DHPA 150 mg + EEn 10 mg sobre cobre, ceruloplasmina, CBG, cortisol libre y total y SHBG fueron escasos o nulos, en comparación con el grupo no hormonal. En cambio las píldoras, inclusive las microdosificadas, mostraron modificaciones de todas esas variables, altamente significativas frente al inyectable (p 0.01) y a los métodos no hormonales (p 0.01), sin que haya diferencias entre éstos últimos. Los resultados sugieren que la potencia hormonal de DHPA 150 mg + EEn 10 mg no es mayor que la de las microdosis orales habituales. Por otro lado, no ofrecen indicios de que ésta fórmula esté sobredosificada no produzca acumulación de efectos en el organismo. Estos hallazgos deben ser tenidos en cuenta al considerar la seguridad del inyectable a largo plazo

Monthly injectable steroid contraceptives and cervical carcinoma.

The World Health Organization Collaborative Study of Neoplasia and Steroid Contraceptives is a large multinational hospital-based case-control study of steroid contraceptives and gynecologic, hepatobiliary, and mammary neoplasms. Monthly injectable steroid contraceptives which contained the long-acting progestogen dihydroxyprogesterone acetofenide plus a shorter-acting estrogen (usually estradiol enanthate) were used by women in two of the countries (Chile and Mexico) from which data were collected. In preliminary analyses of data from Chile (1979-1983), a strong association was observed between use of these products and invasive cervical cancer. Therefore, three additional data sets from these two countries were analyzed in further detail for this report. Analyses of additional data from Chile on invasive cervical cancer (1983-1985) and cervical carcinoma in situ (1979-1986) and of data on invasive cervical cancer from Mexico (1979-1986) failed to confirm the initially observed association. The original finding was probably due to chance, but a causal interpretation cannot be confidently ruled out, and additional studies are warranted.

Estrogen-progestogen once-a-month injectable contraceptives and serum prolactin.

To assess the effect of hormonal monthly injectable contraceptives upon the serum values of immunoreactive prolactin (Prl), three groups of women of reproductive age exposed to different estrogen-progestogen injectable formulation for a minimum of one year were studied. The first group (n = 10) received dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg (DHPA/E2-EN), Group 2 (n = 21) received medroxyprogesterone acetate 25 mg and estradiol cypionate 5 mg (MPA/E2-C) and Group 3 (n = 19) was exposed to norethisterone enanthate 50 mg and estradiol valerate 5 mg (NET-EN/E2-V). A group of IUD users (n = 16) served as the control group. Serum Prl and 17 beta-estradiol (E2) concentration were determined in blood samples (0 and 15 min.) on days 0 (day of last injection), 10, 20 and 30 after last contraceptive injection. The results demonstrated a slight though not significant increase (p greater than 0.05) in serum Prl in the three experimental groups as compared with the IUD control group. This increase in Prl levels observed on day 10 post-last injection never exceeded the upper limits of the normal range (20 ng/ml). Overall, the data demonstrated that the chronic administration of these estrogen/progestogen once-a-month injectable contraceptives does not affect the Prl baseline secretion in women.

O endométrio na anticoncepçäo infetável mensal / Endometrium in the monthly injectable contraception

Foram estudadas as alteraçöes histológicas do endométrio causadas em 30 mulheres por injeçäo intramuscular única da associaçäo de 150 mg de acetofenido de didroxiprogesterona com 10 mg de enantato de estradiol. O uso dessa associaçäo hormonal causou assincronismo na evoluçäo dos parâmetros endometriais, interferiu nos índices cíclicos do muco cervical e foi eficaz na supressäo da ovulaçäo. O fármaco teve açäo predominantemente periférica no endométrio, porém näo causou reaçöes adversas nem sugestivas de malignidade nas mulheres que o usaram

Serum estrogens and ovulation return in chronic users of a once-a-month injectable contraceptive.

To determine whether the long-term exposure to a monthly injectable contraceptive, containing dihydroxyprogesterone acetophenide 150 mg and estradiol enanthate 10 mg, induces significant changes on the serum estrogens profile and ovulation return in women, a study in chronic users was undertaken. Ovarian function was assessed for 3 months following a single injection of the contraceptive agent in a group of women (n = 7) who have been on this formulation for an average period of 6.7 years and in a non-user control group (n = 7). The serum concentrations of 17 beta-estradiol, estrone and progesterone were measured in samples drawn at regular intervals throughout the entire study. The endometrial bleeding pattern was recorded in all subjects. The results indicated that the post-injection serum estradiol maximum levels (exogenous peak) occurred significantly earlier (p less than 0.05) in chronic users as compared with the non-user control group. Baseline serum estrone concentrations were slightly higher in chronic users than those observed in the control group, while the values of serum 17 beta-estradiol did not exhibit significant differences among the two groups. Ovulation was documented within 60-90 days after injection in all subjects from both groups. A similar length of the first bleeding-free period was observed in all participants. The overall data provide evidence of a moderate increase of estrone, one of the still active metabolic conversion products of 17 beta-estradiol, in the sera of chronic users of this combined contraceptive without affecting its pharmacodynamics.

PIP: The effects of longterm exposure to a monthly injectable contraceptive agent containing 150 mg of dihydroxy-progesterone acetophenide and 10 mg of estradiol enanthate on the serum estrogens profile and ovulation return were investigated in 7 women who had been taking this form of fertility control for an average of 6.7 years and 7 previous nonuser controls. Blood samples were taken immediately prior to injection and twice a week thereafter for a total of 3 months. Longterm users were injected 25-30 days after their previous injection, while the nonusers were injected during the early follicular phase of their menstrual cycle. Baseline serum estradiol concentrations were not significantly different between the 2 groups; immediately after injection, however, serum levels of estradiol increased rapidly to attain a maximum value of 314 in longterm users and 283 pg/ml in controls. The time required to reach maximum estradiol levels was significantly less in longterm users (4.2 days) compared with controls (6.3 days). Higher serum estrone levels were recorded at baseline in the chronically exposed women, although there were no significant differences between groups after 30 days. Ovulation was documented 60-90 days after injection in all subjects and endometrial bleeding patterns were the same in both groups. Overall, these data suggest that the slight increase in serum estrone levels associated with longterm use of this injectable contraceptive is not sufficient to produce prolonged ovarian and endometrial function impairment.

Pharmacodynamic assessment of dihydroxyprogesterone acetophenide plus estradiol enanthate as a monthly injectable contraceptive.

The pharmacodynamics of the combination of dihydroxyprogesterone acetophenide (DHPA) and estradiol enanthate (E2-EN) following its intramuscular administration at two doses were studied in 16 healthy women of reproductive age. Subjects were randomly allocated in two groups: group I (n = 9) received the combination DHPA 150 mg + E2-EN 10 mg on three consecutive monthly injections, while group II (n = 7) received half-dose of the same formulation. Ovarian function and endometrial bleeding patterns were investigated in all participants for one pre-treatment cycle, three treatment intervals and two post-treatment cycles. The results disclosed that ovulation was inhibited for at least 30 days following DHPA/E2-EN administration in all participants from both groups. The circulating estradiol levels 30 days after last injection were slightly elevated as compared with those observed in normal early follicular phase. Return to ovulatory cycles was documented within 90 days after treatment. The length of the bleeding-free intervals during treatment was shortened in both groups, particularly in group II. No significant changes in HDL-cholesterol levels were observed throughout the study. It is envisaged however, that large modification of the formulation and additional long-term safety studies will be required prior to its recommendation.

PIP: The pharmacodynamics of the combination of dihyroxyprogesterone acetophenide (DHPA) and estradiol enanthate (E2-EN) following its intramuscular administration at 2 doses were studied in 16 healthy women of reproductive age attending the Family Planning Clinic at General Hospital in Mexico City. Subjects were randomly allocated in 2 groups: group I (n=9) received the combination DHPA 150 milligrams and E2-EN 10 milligrams on 3 consecutive monthly injections, while group II (n=7) received 1/2 dose of the same formulation. Ovarian function and endometrial bleeding patterns were investigated in all participants for 1 pretreatment cycle, 3 treatment intervals and 2 post-treatment cycles. The results disclosed that ovulation was inhibited for at least 30 days following DHPA/E2-EN administration in all participants from both groups. The circulating estradiol levels 30 days after last injection were slightly elevated as compared with those observed in normal early follicular phase. Return to ovulatory cycles was documented within 90 days after treatment. The length of the bleeding-free intervals during treatment was shortened in both groups, particularly group II. No significant changes in HDL-cholesterol levels were observed throughout the study. It is envisaged however, that large modification of the formulation and additional long-term safety studies will be required prior to its recommendation.

Body weight and cycle control of injectable contraceptives.

Five long-acting progestogens were tried as injectable contraceptives in 1,363 women for one to three years. A total of 22,304 woman-months were studied. The first injection was given either within five days of the onset of the menstrual cycle or during the postpartum phase (330 women). The different factors that may influence cyclicity were analyzed. Among these factors, the following may be important: potency and dose of progestogen, addition of long-acting estrogen, pretreatment menstrual pattern, duration of therapy and body weight of users. The incidence of amenorrhea was higher in overweight than in underweight or normal subjects. The causal relationship can be explained by the storage of the absorbed progestogen in the adipose mass.