Does luteal phase progesterone supplementation affect physical and psychosocial well-being among women undergoing modified natural cycle-FET? A sub-study of a randomized controlled trial.

STUDY QUESTION: Are there any differences in physical and psychosocial well-being among women undergoing modified natural cycle frozen embryo transfer (mNC-FET) with or without vaginal progesterone as luteal phase support (LPS)? SUMMARY ANSWER: Women undergoing mNC-FET with vaginal progesterone supplementation were more likely to experience physical discomfort but there was no difference in psychosocial well-being between the two groups. WHAT IS KNOWN ALREADY: mNC-FET can be carried out with or without vaginal progesterone as LPS, which has several side-effects. It is commonly known that fertility treatment can cause stress and psychosocial strain, however, most studies on this subject are conducted in fresh cycle regimes, which differ from NC-FET and results may not be comparable. STUDY DESIGN, SIZE, DURATION: This is a sub-study of an ongoing RCT investigating whether progesterone supplementation has a positive effect on live birth rate in mNC-FET. The RCT is conducted at eight fertility clinics in Denmark from 2019 and is planned to end primo 2024. The sub-study is based on two questionnaires on physical and psychosocial well-being added to the RCT in August 2019. On the time of data extraction 286 women had answered both questionnaires. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who had answered both questionnaires were included in the sub-study. Participants were equally distributed, with 143 in each of the two groups. Participants in both groups received the same questionnaires at two time-points: on cycle day 2-5 (baseline) and after blastocyst transfer. Participants in the progesterone group had administered progesterone for 7 days upon answering the second questionnaire. All items in the questionnaires were validated. Items on psychosocial well-being originate from the Copenhagen Multi-Centre Psychosocial Infertility-Fertility Problem Stress Scale (COMPI-FPSS) and from the Mental Health Inventory-5. MAIN RESULTS AND THE ROLE OF CHANCE: Women receiving progesterone experienced more vaginal itching and/or burning than women in the non-progesterone group (P < 0.001). Women in the progesterone group also experienced more self-reported vaginal yeast infection, this was, however, not significant after adjustment for multiple testing (P/adjusted P = 0.049/0.881). No differences regarding psychosocial well-being were found between the two groups. Within the progesterone group, a shift toward feeling less 'downhearted and blue' was found when comparing response distribution at baseline and after blastocyst transfer (P < 0.001). LIMITATIONS, REASONS FOR CAUTION: All items on physical symptoms were self-reported. The item on vaginal yeast infection was therefore not diagnosed by a doctor. Inclusion in the study required a few extra visits to the clinic, participants who felt more burdened by fertility treatment might have been more likely to decline participation. Women who experienced a lot of side-effects to progesterone prior to this FET cycle, might be less likely to participate. WIDER IMPLICATIONS OF THE FINDINGS: Our results are in line with previous known side-effects to progesterone. Physical side-effects of progesterone should be considered before administration. STUDY FUNDING/COMPETING INTEREST(S): The RCT is fully supported by Rigshospitalet's Research Foundation and a grant from Gedeon Richter. Gedeon Richter were not involved in the design of protocol nor in the conduction of the study or analysis of results. A.P., L.P., and N.I.-C.F. report grants from Gedeon Richter, Ferring and Merck with no relations to this study. N.I.-C.F. has received travel support from Ferring, Merck A/S, & Gideon Richter, and is the head of the steering committee for the Danish Fertility Guidelines made by the members of from the Danish Fertility Society. A.P. reports consulting fees from Preglem, Novo Nordisk, Ferring, Gedeon Richter, Cryos, & Merck A/S, honoraria from Gedeon Richter, Ferring, Merck A/S, Theramex, and Organon, has received travel support from Gedeon Richter (payment to institution), participated on an advisory board for Preglem and was loaned an embryoscope from Gedeon Richter to their institution. A.L.S. has stock options for Novo Nordisk B A/S. B.A. have received unrestricted grant from Gedeon Richter Nordic and Merck and honoraria for lectures from Gedeon Richter, Merck, IBSA, and Marckyrl Pharma. TRIAL REGISTRATION NUMBER: The RCT is registered on ClinicalTrials. gov (NCT03795220) and in EudraCT (2018-002207-34).

My best case: homeopathic management of adverse effects of tamoxifen.

BACKGROUND: Nearly half of patients discontinue tamoxifen hormone therapy early because of side effects, thus increasing the risk of breast cancer recurrence. Could a homeopathic treatment improve compliance? METHODS: A patient suffering from side effects of tamoxifen was seen in consultation every 2 months for 10 months by a senior homeopathic doctor and a registrar. RESULTS: Case analysis and repertorisation led to the identification of Pulsatilla as the simillimum drug and tamoxifen 7c as the etiological treatment. This treatment resulted in a rapid and lasting improvement of all the symptoms. CONCLUSIONS: The combination of a homeopathic medicine and a hetero-isotherapic illustrates both the principles of "similarity" and "the identical". It has proved to be an excellent response to the side effects of tamoxifen. By enhancing the patient's quality of life, this combined approach also improved adherence to treatment.

Complementary and alternative medicine in radiation oncology : Survey of patients' attitudes.

BACKGROUND: Complementary and alternative medicine (CAM) are gaining in importance, but objective data are mostly missing. However, in previous trials, methods such as acupuncture showed significant advantages compared to standard therapies. Thus, the aim was to evaluate most frequently used methods, their significance and the general acceptance amongst cancer patients undergoing radiotherapy (RT). METHODS: A questionnaire of 18 questions based on the categorical classification released by the National Centre for Complementary and Integrative Health was developed. From April to September 2015, all patients undergoing RT at the Department of Radiation Oncology, Technical University of Munich, completed the survey. Changes in attitude towards CAM were evaluated using the questionnaire after RT during the first follow-up visit (n = 31). RESULTS: Of 634 patients, 333 answered the questionnaire (52.5%). Of all participants, 26.4% used CAM parallel to RT. Before RT, a total of 39.3% had already used complementary medicine. The most frequently applied methods during therapy were vitamins/minerals, food supplements, physiotherapy/manual medicine, and homeopathy. The majority (71.5%) did not use any complementary treatment, mostly stating that CAM was not offered to them (73.5%). The most common reasons for use were to improve the immune system (48%), to reduce side effects (43.8%), and to not miss an opportunity (37.8%). Treatment integrated into the individual therapy concept, e.g. regular acupuncture, would be used by 63.7% of RT patients. CONCLUSION: In comparison to other studies, usage of CAM parallel to RT in our department is considered to be low. Acceptance amongst patients is present, as treatment integrated into the individual oncology therapy would be used by about two-third of patients.

China rubra for side-effects of quinine: a prospective, randomised study in pregnant women with malaria in Cotonou, Benin.

BACKGROUND: In endemic areas, gestational malaria is responsible for low birth weight and maternal anaemia. Quinine is the reference treatment for acute malaria in pregnant women, irrespective of term. However, quinine administration is associated with various side-effects. We evaluated the impact of the homeopathic medicine China rubra 7CH on the side-effects of quinine used as treatment for acute malaria in pregnant women in Cotonou, Benin. METHODS: This prospective, comparative, randomised study was carried out between June and December 2007 in the Saint Jean-Baptiste Medical Centre, Cotonou. Women were included if they were >3 months pregnant and had a clinical diagnosis of malaria confirmed by a positive thick blood smear. The study population was divided into two groups: (i) patients who presented between the 1st and 15th of each month and who received China rubra 7CH plus quinine (China group); and (ii) patients who presented from the 16th to the end of each month and who received treatment with quinine only (Standard group). The aim was to compare the frequency of side-effects of quinine in the two groups until day 6 after the start of treatment. Neither the patients nor the care givers were blinded to study treatment. Statistical comparison of the two groups was carried out with an alpha risk fixed at 5%. RESULTS: 211 women were recruited: 105 received quinine plus China rubra 7CH (China group) and 106 received quinine only (Standard group). A decrease in proportion of patients presenting with side-effects was observed in the China group from day 0 to day 6 of follow-up (53.9%-23.3%) whereas the proportion of patients with side-effects in the Standard group did not change significantly (85.9% on day 0 vs. 82.5% on day 6). Ninety-six (72.4%) patients in the China group and 103 (97.2%) in the Standard group reported at least one side-effect during follow-up (p < 0.0001). The most frequently reported side-effects were tinnitus, dizziness and asthenia. CONCLUSIONS: This preliminary study shows the interest of China rubra 7CH in limiting the side-effects of quinine used for the treatment of acute malaria in pregnant women.

Serious Skin Injuries Following Exposure to Unapproved Mole and Skin Tag Removers.

Objective: We sought to describe skin injuries associated with unapproved topical mole and skin tag removers containing concentrated salicylic acid, Sanguinaria canadensis, or other caustic agents. Methods: We identified skin injuries associated with unapproved non-device topical mole and skin tag removers reported to the US Food and Drug Administration (FDA) through October 30, 2021 or described in Amazon consumer product reviews between 2019 and 2021. Results: We identified 38 cases, including 30 from Amazon consumer product reviews and eight reported to the FDA. Twenty-eight were from 2021. The most common reason for use was for mole and/or skin tag removal. Listed ingredients included salicylic acid, Sanguinaria canadensis, botanicals (includes homeopathic products), and calcium oxide. Seven cases involved products without ingredients listed. Adverse events included burns, pain, and ulceration, some resulting in permanent scarring and disfigurement. There were 14 facial injuries, including four adjacent to the eye. Reported treatments included antibiotics, hospital care, wound care, and dermatology advice to have a skin graft. Limitations: Limitations include underreporting of adverse events to the FDA, limited clinical details and potential bias in consumer reviews, and poor replicability of review searches due to the dynamic nature of the Amazon website. Conclusion: Unapproved, non-device topical mole and skin tag removers are associated with serious skin injuries. We found Amazon consumer reviews to be a novel and useful data source for safety surveillance of these types of skin products. When dermatologists are consulted about skin injuries, exposure to these products should be considered in the differential diagnosis.

Factors related to technical management and adverse drug event reporting in independent retail pharmacies in Cali, Colombia.

Independent retail pharmacies are required to have a technical manager responsible for the operation and adverse drug event reporting. In this context the following investigation is developed based on one objective: To establish factors related to the technical management and adverse drug event reporting in independent retail pharmacies in Cali. This is a cross-sectional observational study. Data was randomly collected from an estimated sample of 244 independent retail pharmacies. The results show that storage was the area of greatest implementation, 94% of the assessed pharmacies had a technical manager and 50% of them reported adverse drug events. A technical manager, being a chemist, pharmacist, or pharmacy manager, was associated with having computer equipment and dispensing homeopathic products. Adverse drug event reporting was directly associated with having bibliographic resources and inversely associated with the technical manager being a drug retailer. These data show the factors related to technical management of independent retail pharmacies and adverse drug event reporting were identified.

Amelioration of Levetiracetam-Induced Behavioral Side Effects by Pyridoxine. A Randomized Double Blind Controlled Study.

BACKGROUND: Levetiracetam is a relatively new-generation antiseizure drug approved for the treatment of focal and generalized seizures. Despite its favorable side effect profile and minimal drug-drug interactions, neuropsychiatric side effects are reported in up to 13% of children. A few case series have suggested that supplementation of pyridoxine may mitigate these side effects, but controlled trials are lacking. To address this issue, a randomized interventional study was carried out in a pediatric tertiary hospital to qualify and quantify the potential beneficial effect of pyridoxine in attenuating the neuropsychiatric side effects of levetiracetam in children. METHODS: A total of 105 children with epilepsy who were taking levetiracetam (as a monotherapy or an adjunct) who showed behavioral symptoms coinciding with the start of levetiracetam, were included. Patients randomly and blindly received either a therapeutic (pyridoxine group, 46 of 105, 44%) or a homeopathic dose of pyridoxine (placebo, 59 of 105, 56%). A 30-item behavioral checklist was used to qualify and quantify the behavioral side effects at baseline and at different time points following initiation of treatment. RESULTS: Both placebo and pyridoxine groups experienced a statistical reduction in behavioral scores when compared with baseline. Our study indicated that although there was a placebo effect, the improvement in neuropsychiatric symptoms was more prominent in children who received therapeutic doses of pyridoxine. CONCLUSIONS: These data provide clinicians with pertinent evidence-based information that suggests that a trial of pyridoxine in patients who experience behavioral side effects due to the use of levetiracetam may avoid unnecessary change of antiseizure medications.

[Parents' Willingness to Vaccinate with a COVID-19 Vaccine]. / Impfbereitschaft von Eltern mit einem COVID-19-Vakzin: Die Rolle von Elternschaft und Geschlecht.

BACKGROUND: Parents are faced with a vaccination decision in the context of their own vaccination and that of their children with a COVID-19 vaccine. At present, there is no (complete) vaccination recommendation. RESEARCH QUESTION: The study investigates the willingness to vaccinate of parents of minors and people without children who are minors, in which gender differences in particular are examined. METHODS: The study is based on a random sample (telephone survey, n = 2,014, collected between 12 November and 10 December 2020). The evaluation is primarily based on the sub-sample of people with minors in the household (n = 461). RESULTS: Parents of minors consistently show a lower willingness to be vaccinated with a COVID-19 vaccine than respondents without minors (54.1% vs 71.1%). Fathers show a stronger willingness to be vaccinated than mothers. Furthermore, men are more willing to get their own child vaccinated with a COVID-19 vaccine than are women. CONCLUSIONS: Among parents and especially mothers, a considerable misrepresentation of vaccination risks and frequent beliefs in vaccination conspiracy theories can be observed. Clear and easily understandable information on the effects and side effects of vaccination with a COVID-19 vaccine by relevant institutions and physicians is recommended.

La sudoración compensatoria como efecto secundario en la cirugía de la hiperhidrosis palmar primaria / Compensatory Sweating as a Side Effect of Surgical Treatment of Primary Palmar Hyperhidrosis

Introducción: La sudoración compensatoria es un efecto secundario de la simpaticotomía videotoracoscópica, que tiene una alta incidencia y puede provocar insatisfacción en los pacientes operados. Objetivo: Determinar el comportamiento de la sudoración compensatoria en los pacientes en que se les realizó una simpaticotomía videotoracoscópica por hiperhidrosis palmar. Métodos: Se realizó un estudio retrospectivo, transversal y descriptivo de 42 pacientes que tras la cirugía por hiperhidrosis palmar presentaron sudor compensatorio. Se analizó la incidencia, localización, severidad, afectación de la calidad de vida y nivel de satisfacción. Resultados: Predominó la sudoración compensatoria ligera, la localización en la espalda y el abdomen. Hubo un alto nivel de tolerancia, con solo un paciente insatisfecho y un 100 por ciento de mejoría de la calidad de vida. Conclusiones: La sudoración compensatoria no influyó negativamente en la calidad de vida de los pacientes(AU)

Introduction: Compensatory sweating is a side effect of videothoracoscopic sympathectomy. It presents high incidence and may cause dissatisfaction to operated patients. Objective: To determine the characteristics of compensatory sweating in patients who underwent videothoracoscopic sympathectomy for palmar hyperhidrosis. Methods: A retrospective, cross-sectional and descriptive study was carried out with 42 patients who presented compensatory sweating after surgery for palmar hyperhidrosis. Incidence, location, severity, change in quality of life and level of satisfaction were analyzed. Results: Light compensatory sweating predominated, with location on back and abdomen. There was a high level of tolerance, with only one dissatisfied patient and 100 percent of improvement in quality of life. Conclusions: Compensatory sweating did not influence negatively the patients' quality of life(AU)

An evaluation of the TCu 380Ag and the Multiload Cu375.

The TCu 380Ag (Outokumpu Oy, Pori, Finland) and the Multiload Cu375 (Multilan, Organon, Oss, The Netherlands) were evaluated in 1477 women in a multicenter clinical trial. The intrauterine devices showed similar, low-event rates. Cumulative life-table pregnancy rates were less than 1.0, and continuation rates were approximately 90 per 100 women at 1 year after insertion. The risk of subsequent hospitalization or pelvic infection was low.

PIP: This study evaluated the effectiveness, safety, and acceptability of the TCu 380Ag and the Multiload Cu375 IUDs in a multicenter international trial involving 1499 acceptors. The 2 devices were randomly assigned to women who entered the trial at 5 centers in Yugoslavis, Panama, Costa Rica, and Egypt between September 1980 and June 1982. The median age of the 737 women in the TCu 380Ag group was 26.7 years, with an average parity of 1.8; the median age of the 740 women in the Multiload Cu375 group was 27.5 years, with an average parity of 1.9. At insertion, 6.8% of women in the TCu 380Ag group and 6.2% of those in the Multiload Cu375 group complained of mild pain, 1.1% of women in both groups reported moderate pain, and there were no reports of severe pain. 1-year bleeding and pain removal rates were 3.8; removal rates for other medical reasons were less than 1.0/100 women. Significantly more women in the TCu 380Ag group reported intermenstrual pelvic pain, but this difference was confined to women under 30 years of age. The continuation rate at 1 year was 90.9% for the TCu 380Ag group and 88.7% for the Multiload Cu375 group. These rates are considerably higher than those reported for other IUDs. Of the 7 pregnancies reported in the 1st year after insertion, 2 occurred in the Tcu 380Ag group and 5 occurred in the Multiload Cu375 group. The results from this trial suggest that both the TCu 380Ag and Multiload Cu375 IUDs provide a highly effective, safe, and acceptable method of contraception. For women who wish to achieve contraceptive effectiveness for long periods, the TCu 380Ag may be the IUD of choice. It remains effective for 10-15 years, while the Multiload Cu375 has a life span of only 3-5 years.

Carbohydrate metabolism in women who used oral contraceptives containing levonorgestrel or desogestrel: a 6-month prospective study.

Blood glucose and pyruvate, plasma insulin, and glucagon levels as well as erythrocyte insulin receptors were measured during an oral glucose tolerance test in 38 normal women before and after 6 months' use of one of three new oral contraceptives containing low doses of 19 nortestosterone-derived progestogens, levonorgestrel, and desogestrel. A slight deterioration of glucose tolerance was observed, with the area under the glucose curve increasing by only 7%, 9%, and 12% after Ovidol (Aaciphar SA, Brussels, Belgium), Marvelon (Organon, SA, Brussels, Belgium), and Trigynon (Schering SA, Brussels, Belgium) administration, respectively. We did not find any argument in favor of the development of a state of insulin resistance in women using these compounds, because erythrocyte receptor binding was not modified and plasma insulin responses to glucose were decreased. The glucose-induced suppression of plasma glucagon levels seemed less effective for treatment with the desogestrel-containing preparations than with the levonorgestrel-containing oral contraceptives.

Clinical evaluation of a new oral contraceptive, 'Pregnon'.

'Pregnon', a new oral contraceptive containing 1 mg. lynestrenol and 0.05 mg. ethinyl oestradiol, was administered cyclically to 639 women of fertile age over a total of 9,159 cycles. There were no pregnancies. In most cases the withdrawal bleeding resembled normal menstruation. The incidence of metrorrhagia was relatively low and when it did occur it was usually confined to the early treatment cycles and was of very limited duration. The objective and subjective tolerance was excellent.

PIP: Pregnon is a new low-dosage ovulation-inhibiting agent containing 1 mg of lynestrenol and .05 mg of ethinyl estradiol in each tablet. It is also marketed under the name of Pregnon 28 or Ovostat 28 in which each package contains 22 active plus 6 placebo tablets. Data were collected from Belgian clinics and evaluated by the Medical Unit of Organon in Belgium and the Netherlands. During this study, 639 women of fertile age were monitored through 9159 cycles. The maximum period of treatment was 36 cycles. Clinical and gynecological examinations were made before treatment and then every 2 or 3 months. Treatment was begun by taking the 1st tablet on the 1st day of menstruation. After taking 22 tablets there was a 6-day tablet-free interval during which withdrawal bleeding usually occurred. The intensity of the withdrawal bleeding was normal in 57.3%, slight in 41.7%, and heavy in 1%. Spotting was noted in 3.1% of the cycles and breakthrough bleeding occurred in 2.9%. Usually they occurred in the first 3 cycles. Amenorrhea was observed in 2.9% of the cycles. Body weights were relatively unchanged. Blood pressures remained the same. Side effects were headache, nausea, vomiting, breast tenderness, heavy legs, leucorrhea, nervousness, depression, and decreased libido. Only 46 patients discontinued treatment because of these drug effects yielding an acceptability level of about 93%. Since no pregnancies occurred during this study, the Pearl index was 0.

A cross-over study of three oral contraceptives containing ethinyloestradiol and either desogestrel or levonorgestrel.

A randomised cross-over trial was performed to compare the pharmacodynamic actions of three low-dose oral contraceptives (OCs): Marvelon (150 micrograms desogestrel (DSG)+ 30 micrograms ethinyloestradiol (EE)), Mercilon (150 micrograms DSG + 20 micrograms EE) and Microgynon (150 micrograms levonorgestrel (LNG) + 30 micrograms EE). None of the OCs produced any significant changes in serum cholesterol, LDL-C and apoprotein B. Triglycerides were increased by the desogestrel OCs but not by Microgynon. The latter however increased the glucose and insulin responses to a glucose tolerance test whereas Marvelon and Mercilon had no effect. HDL-C increased with Marvelon, was unchanged with Mercilon and was decreased with Microgynon. Apoprotein AII was increased by all three OCs but only the DSG OCs increased apoprotein AI. All OCs produced similar increases in caeruloplasmin but the increase in SHBG was much greater with Marvelon and Mercilon than with Microgynon. Testosterone was reduced more with Microgynon than with the DSG OCs. Many of the changes reflect the strong anti-oestrogenic action of LNG on metabolic parameters compared to DSG. Except for the effect on HDL-C, there was little difference between Marvelon and Mercilon on metabolic parameters and this complements the findings from large-scale clinical trials of the two OCs. Mercilon, therefore provides a very satisfactory alternative to Marvelon.

PIP: 12 healthy volunteers attending the family planning clinic at Shanghai, First Maternity and Infant China, Hospital, enrolled in the study, Oral contraceptives (OCs) were prescribed: Marvelon (150 mcg of desogestrel--DSG), Mercilon (150 mcg of DSG), and Microgynon (150 mcg of levonorgestrel--LNG). The patients were divided into 6 groups of 2 persons each in a randomized cross-over study. OCs were taken on day 6 of the cycle up to day 21, then stopping for 7 days. Each OC was used for 3 months. During the pretreatment cycle between days 6 and 9 of the follicular phase and 21 and 22 of the luteal phase a blood sample was taken after fasting for determination of lipids, sex hormone binding globulin (SHGB), ceruloplasmin, and testosterone. After glucose loading, significant increases of glucose and insulin occurred at 1, 2, and 3 hours during treatment with Microgynon only. The ratio for total areas of insulin to glucose did not change significantly nor did glycosilated hemoglobin A1 levels. Serum triglyceride concentrations increased significantly for both Marvelon (27%-43%) and Mercilon (29-40%). Serum high density lipoprotein (HDL) cholesterol concentrations were significantly elevated with Marvelon but less so with Mercilon, while HDL-C decreased significantly with Microgynon. The serum low density lipoprotein (LDL) cholesterol changes were not significant, but LDL-C concentrations declined with DSG formulations and increased with Microgynon. Apoprotein A1 and A2 increased significantly for both Marvelon and Mercilon. Apoprotein A2 increased with Microgynon. Serum SHBG increased markedly with Marvelon (335-380%). Serum testosterone concentrations decreased significantly (33.2-40.4% with Microgynon) and so did ceruloplasmin values. The antiestrogenic effect of strong LNG in Microgynon produced significant metabolic changes. The effect of 30 mcg EE in Marvelon and 20 mcg EE of Mercilon was equal.

Clinical comparison of two low-dose oral contraceptives, Minulet and Mercilon, in women over 30 years of age.

A comparative study of two low-dose oral contraceptives, gestodene (GES) 75 mcg/ethinyl oestradiol (EE) 30 mcg and desogestrel (DES) 150 mcg/EE 20 mcg, was conducted in women over 30 years of age. This randomised, open-label study was organised in Denmark, Italy, New Zealand and United Kingdom. A total of 505 women received GES/EE and 501 received DES/EE for 6 consecutive menstrual cycles. The two groups were comparable in terms of demographic and gynaecologic characteristics at baseline. However, the menstrual flow length was slightly longer in the GES/EE group before the start of the treatment. The mean age (+/- SD) was 35 +/- 4 years in the GES/EE group and 35 +/- 5 years in the DES/EE group. The subjects in the GES/EE group contributed data for a total of 2800 cycles and those in the DES/EE group, data for 2796 cycles. There were no pregnancies on medication with either preparation. The results showed that there were significantly more normal cycles in the GES/EE group for cycles 1 to 6. Irregular bleeding between withdrawal bleeds occurred in 10% of GES/EE and 18.5% of DES/EE cycles. Absence of all bleeding was reported in 29 (1%) and 63 (2%) cycles, respectively. The incidence of missed pills was low in both groups (11% of cycles). No significant differences were observed in cycle length or withdrawal bleeding episode length. Withdrawal bleeding mean intensity was statistically significantly greater with GES/EE. However, for both preparations, the mean intensity was close to light bleeding. No clinically significant differences were noted in weight, blood pressure, Papanicolaou smears or laboratory data. Sixty-eight (13.5%) subjects in the GES/EE group and 64 (12.8%) in the DES/EE group discontinued before the end of the study. Among them, 37 (7%) and 40 (8%) in the respective groups withdrew because of adverse reactions. There was no difference between groups in terms of primary reasons for withdrawal. The most frequently reported complaints that led to discontinuation in both groups were headache, nausea and metrorrhagia. Breast tenderness led to the discontinuation of 1 subject in the GES/EE group and 3 in the DES/EE group. These results show excellent cycle control, efficacy and very low rate of side effects with both GES/EE and DES/EE. These low-dose oral contraceptives could be well suited to healthy nonsmoking women requiring contraception up to the age of menopause.

PIP: At 66 sites in Denmark, Italy, New Zealand, and the UK, clinicians randomly allocated 1006 women 30 years old, some of whom were in their early 50s, into 1 of 2 groups receiving a low-dose oral contraceptive (OC): Minulet containing 75 mcg gestodene (GES)/30 mcg ethinyl estradiol (EE) and Mercilon containing 150 mcg desogestrel (DES)/20 mcg EE. The study aimed to compare these 2 low-dose OCs to help physicians prescribe an OC that could be continued into later years. Before treatment, the 2 groups had similar demographic and gynecologic characteristics. The mean menstrual flow length in the GES/EE group was longer than that of the DES/EE group (4.7 days vs. 4.5 days; p = .035) though. None of the women during 2800 cycles of GES/EE use and 2796 cycles of DES/EE use conceived, even though women forgot to take at least 1 pill in 11% of cycles. The GES/EE OC had significantly better cycle control than did the DES/EE OC. For example, the GES/EE group was more likely to have normal cycles than the DES/EE group (84-93% vs. 73-83%; p .001). The DES/EE group experienced a significantly lower withdrawal bleeding mean intensity than the GES/EE group in all 6 cycles, but the bleeding for both groups was close to light bleeding. The 2 groups were similar in weight, blood pressure, Papanicolaou smears, and laboratory data. Discontinuation rates for the GES/EE and DES/EE groups were 13.5% and 12.8%, respectively. Adverse reactions accounted for discontinuation in 7% of the GES/EE group and 8% of the DES/EE group. The major complaints leading to discontinuation were headache, nausea, and breakthrough bleeding. Both GES/EE and DES/EE had very good cycle control and efficacy and a very low rate of side effects. These results suggest that both these low-dose OCs would be acceptable for healthy nonsmoking women needing contraception up to menopause.

Hemostatic and metabolic effects of lowering the ethinyl-estradiol dose from 30 mcg to 20 mcg in oral contraceptives containing desogestrel.

The metabolic and hemostatic effects of two oral contraceptives containing 150 mcg desogestrel and 20 mcg ethinyl-estradiol (EE) (MERCILON) or 30 mcg EE (MARVELON) were compared in order to examine the effect of reducing the EE dose in contraceptive pills. Forty-nine women participated in this randomized study during 6 cycles. In both groups, there was a significant increase in triglycerides, HDL-cholesterol and apoprotein A1; the same increase was observed for SBP and CBG. Slight and transient variations of fasting blood glucose levels were seen in the 30 mcg EE group and in the two groups for fasting insulin levels. The increase in renin substrate was significantly higher with the 30 mcg EE than with the 20 mcg EE pill. In both groups, plasminogen increased significantly, but antithrombin III, total and free protein S and fibrinogen decreased significantly only in women taking the 30 mcg EE pill, whereas there was no significant change in the 20 mcg EE group. Reducing the dose of EE in oral contraceptives from 30 mcg to 20 mcg minimizes their impact on renin substrate and hemostatic parameters.

[Minipill as the new contraceptive method]. / Que faut-il penser de la "minipill" en tant que nouvelle méthode contraceptive.

PIP: The efficacy, side effects, and biologic actions of the progestogen-only minipills marketed since February 1973 are reviewed. The preparations are: 350 mcg norethisterone (Micronor Ortho), 30 mcg d-norgestrel (Microlut Schering and Microval Wyeth), and 500 mcg lynestrenol (Exluton Organon). The efficacy of these drugs depends on motivation: Pearl indexes vary from 1.17-3.72 for norethisterone, .9-4.4 for d-norgestrel, and .8- 2.2 for lynestrenol. Some physiologic effects of minipills possibly related to their mode of action are impermeable cervical mucus and low levels of progesterone, pregnanediol, estrogen, and LH. The side effects influencing dropout most are spotting (40-55% in the first cycle), polymenorrhea (about 10%), and amenorrhea (about 5-10%). Some transient estrogenic side effects such as nausea, headaches, and breast pain may be due to estrogenic metabolites from lynestrenol and norethisterone. None of the severe estrogenic side effects, such as thrombophlebitis and impaired glucose tolerance and liver function, are characteristic of progestogen pills.^ieng

[Clinical effectiveness of Marvelon]. / Analiza kliniczna stosowania Marvelonu.

Clinical results of a new contraceptive pills--Marvelon (Organon) were studied. 32 women, ages 30 +/- 5 years, participated in the study during at least 6 cycles. Marvelon was good tolerated and subjective side-effects were very low. The cycles were regular, duration of withdrawal bleeding was 3-5 days and the amount of the blood lost were unchanged or milder. Marvelon didn't affect body weight and blood pressure. Favourable lipid profile--increased a mean level of HDL-Cholesterol and decreased a mean level of LDL-Cholesterol were noticed. Pearl Index was 0,0.

PIP: Marvelon is an oral contraceptive of the third generation of contraceptives introduced in the 1980s. These preparations contain progestagens (desogestrel, gestodene, and norgestimate) and ethinyl estradiol. Marvelon contains .03 mg of ethinyl estradiol and .15 mg of desogestrel. The results of clinical use of Marvelon (made by Organon), were studied in 32 women aged 30 +or- 5 years in the course of at least six cycles. Marvelon was well tolerated and the subjective side effects were minor. The cycles were regular and withdrawal bleeding lasted 3-5 days. The duration of menstrual cycles with the use of Marvelon constituted 27-30 days. The amount of bleeding did not change in 26 women, while it became less in 6 women. Marvelon did not affect body weight and blood pressure. The weight of the patients varied within the limit of +or- 2 kg. It produced a favorable lipid profile by increasing the mean level of high density lipoprotein (HDL) cholesterol and lowering the mean level of low density lipoprotein (LDL) cholesterol. The level of HDL cholesterol was 1.56 mmol/l in cycle 0 compared with 1.85 in cycle 6. The average level of LDL cholesterol was statistically lower in the 6th cycle of Marvelon use (2.73 mmol/l) in comparison to cycle 0 (3.29 mmol/l). Marvelon did not significantly influence the values of glucose, total cholesterol, and triglycerides. The Pearl Index was 0.0.

[A clinical trial with the monophasic contraceptive Marvelon]. / Klinichen opit s monofazen kontratseptiv--Marvelon.

The authors present their clinical experience with a monophasic preparation consisting of 30 mcg ethynyl estradiol and 150 mcg desogestrel (Marvelon, Organon). 121 cycles of 24 fertile women were followed. The results show a full contraceptive success, a stable cycle control as well as a low incidence of the side effects.

PIP: The objective of the study was to assess the clinical effectiveness of the monophasic oral contraceptive Marvelon by examining its safety and its effectiveness in controlling the menstrual cycle as well as the frequency and types of side effects. 24 healthy women with an average age of 24.5 years (range of 18-33 years) were the subjects. 23 had previous reproductive events: 18 births, 5 spontaneous abortions, and 16 induced abortions. 17 women had used contraceptives sporadically: 3 postcoital pills, 8 triphasic pills, and 6 monophasic pills. During the year prior to initiating Marvelon use 2 women had experienced oligomenorrhea, 5 had had hypermenorrhea, 6 had had dysmenorrhea, and 3 had had irregular uterine bleeding. The observation period of contraceptive use lasted 4-6 months, during which a total of 121 cycles were evaluated without one single case of pregnancy. This meant a 100% contraceptive safety or a Pearl index of 0. 20 of the patients had stable cycles. 4 women with 13 of the 121 cycles (10.5%) had menstrual disorders. There were 5 cases of breakthrough bleeding and 8 cases of spotting. Weak dysmenorrhea occurred only in 2 patients. Other side effects included: nausea (2), headache (2), nervousness (2), mastodynia (3), vertigo (1), depression (1), and increase of body weight (2). As the duration of taking Marvelon increased the frequency of menstrual disorders declined. Not a single case of post-pill amenorrhea occurred. At the present time over 5 million women use Marvelon in the world. Epidemiological studies involving 14,903 women with a total of 98,225 menstrual cycles have revealed only 4 pregnancies or a Pearl index of 0.06. In the present study regular pseudomenstrual bleeding was confirmed in 89.5% of investigated cycles, which compares to 96.1% indicated in the literature. Marvelon proved to be a modern, safe contraceptive with stable control of the menstrual cycle, and which exhibited only minor side effects.

La homeopatía como propuesta válida para la atención primaria de salud / Homeopathy as a valid proposal for primary health care

Se plantea un análisis de la pertenencia histórica del empleo de la homeopatía, con valiosos datos que aparecen desde el siglo XIX en Cuba. Actualmente es una terapéutica de elección, tanto en países desarrollados como en vías de desarrollo, se estima que millones de personas son atendidas cada año con productos homeopáticos que además tienen muy bajos reportes de reacciones adversas. A partir de interrogantes tales como: ¿puede la homeopatía superar sus debilidades e impactar en la comunidad científica?; ¿existe certidumbre dentro de la ciencia que apoye la utilidad de la homeopatía para el médico de atención primaria de salud?; ¿conseguirá la homeopatía convertirse en herramienta terapéutica en la atención primaria de salud? Se pretende aclarar la validez de esta disciplina clínica para el médico de la familia, en su labor comunitaria, ya que es el único especialista que atiende integralmente a la familia con un enfoque clínico-epidemiológico. La homeopatía le ofrece la posibilidad de tratar al niño desde que es recién nacido, a la embarazada, al adulto y a los ancianos, tanto en sus enfermedades crónicas, como en las agudas e incluso en epidemias; además, puede contribuir a que mejore la calidad de vida de estos pacientes

We propose an analysis of historical association of using homeopathy with valuable data that appears from the nineteenth century in Cuba. Today it is a therapeutic choice in both developed and developing countries, it is estimated that millions of people are treated each year with homeopathic products, which also have very low adverse reaction reports. From such questions as: Can homeopathy overcome their weaknesses and impact in the scientific community? Is there certainty in science that supports the usefulness of homeopathy for the primary health care? Will homeopathy become a therapeutic tool in primary health care? It seeks to clarify the validity of this clinical discipline for the family physician in his/her community work, since it is the only specialist, who fully assists the family with a clinical and epidemiological approach. Homeopathy offers the possibility to treat children including the newly born, pregnant women, adults and the elderly, in their chronic and acute diseases, as well as in epidemics. It can also contribute to improve the quality of life for these patients

Shortened pill-free interval delivered by new 20 mcg pill. Organon's Mircette scheduled for U.S. debut this summer.

PIP: The new low-dose oral contraceptive (OC), Mircette, is the first pill to shorten the hormone-free interval. The dosing regimen begins with 21 days of 20 mcg of ethinyl estradiol and 150 mcg of desogestrel; the last 7 days start with 2 days of placebo, followed by 5 days of 10 mcg of ethinyl estradiol. These 5 days of ethinyl estradiol are expected to oppose the effect of any follicle-stimulating hormone in promoting growth of a follicle in the estimated 20% of pill takers who are close to ovulation at the end of each pill-free interval. The efficacy trial, which included more than 1000 women followed for 18 menstrual cycles, reported a Pearl index of 1.02. Breakthrough bleeding occurred in 3.5% of the 18 cycles. Less than 3% of women discontinued Mircette use because of menstruation-related side effects. The small amount of estrogen provided by Mircette during the last 5 days of the cycle helps prevent the withdrawal headaches many users of OCs with a longer hormone-free interval experience. Mircette will become available in the US in July 1998.^ieng