Pituitary response to LHRH in long-term users of injectable contraceptives

The site of gonadotrophin inhibition in longterm users of injectable contraceptives is still debatable. The pituitary response to LHRH (50 ug, I.V.) was assessed in 32 women. Sixteen cases were using either medroxyprogesterone acetate (DMPA; n = 8 150 mg I.M. every three months) or norethisterone enanthate (NET-EN; n = 8, 200 mg every 2 months) for at least 18 months. The remaining cases (n = 16) were normal fertile females not using any hormonal contraceptive (control group). The pituitary response to LHRH injection in both injectable subgroups was nearly identical to that in the control group. Neither the basal levels nor the net increase in gonadotrophins following LHRH injection were significantly different in the study groups from those of the control group. Long-term use of DMPA or NET-EN does not affect the pituitary responsiveness to LHRH injection and the pituitary is not a primary site for ovulation inhibition in these cases.     

Temporary discontinuation: a compliance issue in injectable users.

This study examined compliance in injectable users and followed women post-discontinuation to document their contraceptive practices. A cohort of 189 predominantly new users of depot-medroxyprogesterone acetate and norethisterone oenanthate were recruited and followed for 2 years regardless of whether or not they continued the method. Continuation rates were 42% at 1 year and 21% at 2 years. Of the 78 women who discontinued the method, 31 reported that they were "taking a break." For 20 of these women, this break (nonuse segment) occurred within the 2-year period, and 15 of them returned to the injection before the end of study period. The other five switched methods after the nonuse segment. The mean length of the nonuse segment was 7 months (range 2-13 months). In all 20 women, no other contraceptive method was used, they remained sexually active, and started the break within 6 months of commencing use of the injectable. In addition, 11 women were in a self-reported nonuse segment at the end of the study and stated their intention to return to the method at a later date. Menstrual disturbances were cited as the main reason for the break. Strengthened counseling at method acceptance was identified as a strategy to decrease the frequency of breaks in injectable method use.     

Endometrial histology in long-term users of the once-a-month injectable contraceptive Cyclofem

This study evaluated endometrial histology in women using the once-a-month injectable contraceptive Cyclofem for one year or more. The study received IRB approval. Seventeen Cyclofem users accepted to be submitted to an endometrial biopsy. All the samples were collected with an endometrial suction curette (Z-Sampler, ZSI Gynecological Product, Chasworth, CA, USA) in an outpatient clinic, 27–33 days after the last injection. The material was fixed immediately in Bouin solution prior to wax embedding and screened as a routine histological examination by a senior pathologist. The pathologist did not know the bleeding status of each woman or the number of injections each woman had received before the biopsy. All women recorded bleeding and spotting for the last 60 days prior to the biopsy. The mean age of volunteers was 25.9 years (range 21–32) and the mean number of injections received was 24.8 (range 14–47). The results were: 4 out of 17 biopsies were found to be inadequate for diagnosis because they consisted of only blood and mucus. Two of these women were bleeding regularly and the other 2 had amenorrhea. Eight endometrial samples presented a proliferative pattern and, in this group, 3 women had amenorrhea and 5 were bleeding regularly. The other 5 biopsies were reported as secretory endometrium, and 4 of them showed pseudodecidual reaction compatible with the administration of progestin. All of these women were bleeding regularly. The results of the biopsies were not related to the number of injections received nor to the age of the women. In conclusion, long-term administration of the injectable contraceptive Cyclofem did not produce adverse alterations in the endometrium as hyperplasia.     

Human vaginal histology in long-term users of the injectable contraceptive depot-medroxyprogesterone acetate

Objectives

Apparently, depot-medroxyprogesterone acetate (DMPA) increases a woman's risk of acquiring HIV. The objective of this study was to test whether the vaginal mucosal thickness and Langerhans cell counts were significantly different in long-term DMPA users compared with women users of an intrauterine device (IUD) who had never used DMPA.

Study design

Cross-sectional study. Twenty-three DMPA users were matched with 23 nonusers controlled for age, body mass index (BMI; kg/m²), and duration of contraceptive use. Four groups of women were evaluated according to the duration of DMPA use: > 1, < 5; ≥ 5, < 10; ≥ 10, < 15 or ≥ 15 years. Estradiol (E₂) levels were compared between the two groups. Histologic sections of vaginal mucosal biopsies were evaluated to measure the mean epithelial thickness and S100 immunostained sections were used to count the number of Langerhans cells/mm.

Results

Mean (± S.D.) E₂ levels were significantly lower in DMPA users (39.4±26.6 pg/mL) compared with nonusers (102.6±60.3 pg/mL) despite similar ages (42.3±7.4 and 42.4±7.4 years, respectively). Mean (± S.D.) vaginal thickness was 232.6±108.1 and 229.7±112.9 in DMPA users and nonusers, respectively. There were no differences in vaginal thickness or Langerhans cell count/mm between users and nonusers even after controlling for DMPA duration of use.

Conclusions

Vaginal epithelial thinning or Langerhans cell count was not different between long-term DMPA users and copper-IUD users who had never used DMPA.

Implications

No differences were found in vaginal epithelial thickness or in Langerhans cell count between long-term users of the injectable contraceptive DMPA and nonusers.     

Malaria in intravenous drug users associated with HIV seropositivity]

Cases of induced malaria have been notified in S. Paulo State, Brazil, in recent years. At the same time the number of cases imported from endemic regions of Brazil has been increasing. One case of induced malaria by Plasmodium vivax was registered in Presidente Prudente, located in the west of the State, in 1988 and a further eleven cases in 1989. This city is considered to be one of the main transit ports for people who come into the State from the Amazonian region. The patients declared that they had not been to any possible transmission area of malaria. All of them had, however, taken cocaine, sharing the same contaminated needle and syringe. Previously, one person with imported malaria was detected, who had transmitted the disease to the first case in 1988 and also to a further group of 3 people in 1989. One of these three latter cases then transmitted the disease to two other people. As the group of people continued to use the drug among themselves, 2 new cases arose. Afterwards, they re-infected themselves again (one of the was re-infected twice). The test for Human Immunodeficiency Virus was positive for 5 individuals, of whom one had a negative result and 2 others did not undergo the test. This information is discussed within the present context.     

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 nonuser control group (n = 7). The serum concentrations of 17β-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 < 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 17β-estradiol did not exhibit significant differences among the two groups. Ovulation was documented within 60–91 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 17β-estradiol, in the sera of chronic users of this combined contraceptive without affecting its pharmacodynamics.     

An outbreak of Plasmodium vivax malaria among heroin users in Spain

We report the first outbreak of induced malaria among heroin users in Spain, and the first one caused by Plasmodium vivax in Europe. Five drug addicts from Madrid, who had never travelled to endemic areas, were admitted to hospital with fever and splenomegaly. Four had P. vivax malaria with low parasitaemia, ranging from 1 to 3% red blood cells. The fifth case was considered a "seropositive contact" because he had fever and positive malaria indirect fluorescent antibody test but negative blood smear. The source of infection was a young drug addict, who had often travelled to Equatorial Guinea. Another heroin user with a diagnosis of malaria refused to be admitted to our hospital for further study. All had shared contaminated injection equipment. Treatment with chloroquine was effective and none had recrudescence of malaria during a mean follow-up of six months. Drug addicts with unexplained fever may have been infected by malaria transmitted by sharing injections.     

Tuberculosis outbreak in marijuana users, Seattle, Washington, 2004

Matching Mycobacterium tuberculosis isolates were noted among 11 young tuberculosis patients socially linked through illicit drug-related activities. A large proportion of their friends, 14 (64%) of 22, had positive tuberculin skin-test results. The behavior of "hotboxing" (smoking marijuana inside a closed car with friends to repeatedly inhale exhaled smoke) fueled transmission.     

A study of adrenal corticol function and its reserve activity in long-acting injectable contraceptive users

Adrenal function and its reserve capacity were studied in eighteen healthy non-lactating women who received depot-medroxyprogesterone acetate (DMPA: 9 subjects) and norethisterone enanthate (NET-EN: 9 subjects) as long-acting injectable contraceptives. Methodological assessments included: (i) morning fasting concentration of serum cortisol; (ii) diurnal variation of adrenal corticol activity as evidenced by cortisol concentration in serum samples taken at 0700 and 1600 hours; (iii) urinary free cortisol excretion; and (iv) cortisol response to insulin-induced hypoglycaemia. None of these assessments was significantly altered by contraceptive administration. This finding indicates that the subject's ability to release cortisol in response to a stressful situation, as well as to normal day-to-day activity, was not impaired by these contraceptive steroids.     

Vaginal wetness: an underestimated problem experienced by progestogen injectable contraceptive users in South Africa

This paper reports on the common experience of vaginal wetness amongst South African users of progestogen-only injectable contraceptives. The observations emerged in the course of a community-based cross-sectional household survey undertaken in a rural district of KwaZulu-Natal in South Africa. The purpose of the survey was to elicit self-reporting on side effects of injectable contraceptive methods. Eight hundred and forty-eight women aged 15-49 were interviewed and 22.1% reported current use of an injectable contraceptive method, either depot medroxyprogesterone acetate (Depo-Provera) or norethisterone oenanthate (Nur-Isterate). Other modern methods used were oral hormonal contraceptives (4.5%), male condoms (1.3%), the intrauterine device (0.1%), and tubal ligation (0.1%). Vaginal wetness was reported by 18.4% of users and was one of the most common side effects, second only to amenorrhoea (62.5%). It was also what 17.5% of the women liked least about using this method. According to almost half the respondents, men regard women who use the injectable contraceptive as "wet", "cold" and/or "tasteless". These survey findings were supported by participants of 14 focus group interviews held in the sub-district. Since some South African men may prefer dry sex the perception that the injectable contraceptive increases vaginal wetness may be problematic for women who use it. Whilst vaginal wetness can only be classified as a subjective side effect at this stage, further investigations are needed as many South African women opt to use this method.     

Malaria outbreak in a malaria-free region in Oman 1998: unknown impact of civil war in Africa

Beginning in April 1998, the surveillance system in Dhofar region, Oman, detected malaria cases among individuals who had no risk factors for the acquisition of malaria. An investigation was conducted to describe the outbreak and to identify its possible causes. A malaria case was defined as an unexplained fever (>38 degrees C) in a resident of the Dhofar region from April to September 1998. The investigation consisted of enhanced passive case detection, active case finding through contact screening, mass blood survey and school survey. Also an entomological survey was conducted and meteorological data was reviewed. Over a period of seven months, 1279 patients with fever were examined for malaria parasites. Sixty-five cases were positive; 60 (92%) males and 5 (8%) females. Cases occurred in all age groups (range: 2-63 years, median 25 years). Most cases were among illegal Somali immigrants (28, 43%) followed by Omanis (20, 31%). Out of the 2323 slides collected from the community and 2487 from school children, 21 slides were positive. All of them were from illegal immigrants. The entomological survey detected three vectors, previously found in the region: A. d'thali, A. sergenti and A. stephensi. Although the region is classified as a malaria-free region, it has the potential for malaria introduction. This outbreak most likely occurred due to the influx of hundreds of illegal Somali immigrants due to the civil war into the Dhofar region, providing a sufficient number of gametocyte carriers for local anopheline mosquitoes to feed on.     

An outbreak of acute hepatitis B infection among injecting drug users in Inverclyde, Scotland

This large outbreak of acute hepatitis B infection among injecting drug users (IDUs) was precipitated by an increase in injecting heroin use in Inverclyde in the West of Scotland, between 1997 and 1999. Ninety-two cases of hepatitis B infection in residents of Inverclyde were reported to Argyll and Clyde Health Board from January 1996 to December 1999. An investigation of risk factors found 87% (80/92) of the cases were IDUs, of whom four-fifths were men. Fifty six per cent of cases were aged 20-29 years old and 12% were aged 16-19 years old. Further investigations among this close community of young and relatively inexperienced IDUs revealed that many admitted to sharing injecting equipment particularly spoons, water and filters. Only a minority had been using local needle exchange facilities in the area. After public consultation a second needle exchange was opened in 1998 staffed by a dedicated needle exchange development worker who has continued to develop harm reduction services locally.