Best practice in management of paediatric and adolescent hydrosalpinges: a systematic review.

BACKGROUND: Hydrosalpinx is a rare cause of abdominal pain in paediatric patients, though cases are documented in the literature. Its aetiology differs considerably from traditional hydrosalpinx due to ascending sexually transmitted infection. Hydrosalpinx can present mimicking an acute abdomen or can be asymptomatic. Management of paediatric hydrosalpinx varies, but often involves surgical removal of the affected tube. METHODS: In June 2015, a literature search using relevant keywords was completed on MEDLINE and EMBASE databases to determine best management of paediatric hydrosalpinx. RESULTS: We found 66 cases from 38 articles. Surgical intervention took place in 74% of cases (n=49). The most common surgical intervention was salpingectomy. In 3% of cases (n=2), nonsurgical medical management with hormonal therapy was utilized, with post-operative improvement in symptomology. In 23% of cases (n=15), conservative management was utilized: 2 of these cases torted, 4 cases persisted and 9 cases resolved. CONCLUSION: Overall, the results of this review demonstrate that there are comparable outcomes between surgical, medical and conservative management. However, medical and conservative management was not often offered, and more research is needed on the subject.

Successive and cyclic oral contraceptive pill pretreatment improves IVF/ICSI outcomes of PCOS patients and ameliorates hyperandrogenism and antral follicle excess.

OBJECTIVES: To evaluate different oral contraceptive pill (OCP) pretreatment associated differential in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) outcomes of polycystic ovary syndrome (PCOS) patients and explore enhanced hormonal balance induced by the pretreatment. METHODS: This retrospective study included 500 PCOS women and 565 normal ovulating counterparts undergoing IVF/ICSI. The PCOS patients were divided into three groups based on the OCP pretreatment regimens: non-OCP (without OCP pretreatment), unsuccessive OCP (the period of successive pretreatment ≤2 months) and successive OCP (the period of successive pretreatment ≥3 months) groups. Comprehensive hormonal and ultra-sonographic assessments were performed before/after IVF pretreatment. Confounding factors affecting pregnancy outcomes were analyzed with logistic regression. RESULTS: PCOS patients with significant endocrine disorders had reduced implantation and pregnancy rates and increased miscarriage rate. Successive, not unsuccessive OCP pretreatment, significantly improved the implantation and pregnancy rates, and reduced the incidence of monotocous small-for-gestational age infants, which was accompanied by remarkably decreased hyperandrogenism and antral follicles. CONCLUSION: PCOS is an independent risk factor for poor IVF outcome. Successive, not unsuccessive, OCP cyclical pretreatment could improve pregnancy outcome of PCOS patients, associated with reduction of hyperandrogenism and antral follicle excess.

Changes in the size of rectovaginal endometriotic nodules infiltrating the rectum during hormonal therapies.

PURPOSE: To evaluate the changes in the volume of rectovaginal endometriotic nodules infiltrating the rectum during 12-month treatment with hormonal therapies. MATERIALS AND METHODS: This prospective, non-randomized, self-controlled clinical trial included patients with rectovaginal endometriotic nodules infiltrating at least the muscularis propria of the rectum, who received one of the following therapies: norethisterone acetate, triptorelin and tibolone, norethisterone acetate and letrozole, desogestrel, sequential oral contraceptive pill. The volume of the nodules was determined by virtual organ computer-aided analysis (VOCAL, GE Healthcare, USA) at baseline and after 6 and 12 months of treatment. RESULTS: Eighty-three women (90.2 %) completed the 12-month treatment. When compared with baseline values, the volume of the nodules decreased at 6-month (p < 0.001) and 12-month treatment (p < 0.001). After 12-month treatment, the volume of the nodules decreased in all study groups. The volume of the nodules decreased during therapy in 68 women (73.9 %) and increased in 11 women (12.0 %). CONCLUSION: 12-month administration of hormonal therapies reduces the volume of rectovaginal endometriotic nodules infiltrating the rectum in the majority of cases.

[Peripheral blood lymphocyte subpopulations of postmenopausal women with hormone replacement therapy]. / Lymphozytendifferenzierung im peripheren Blut von Frauen unter Hormonsubstitution im Klimakterium.

The effect of hormone replacement therapy on cellular immunity of postmenopausal women was studied by flow cytometry (FACS). Lymphocyte subsets in peripheral blood before and after hormonal replacement therapy (HRT) were measured. After 6 months of HRT with the sequential combined drug Klimonorm(R) (2 mg estradiol valerate and 0,15 mg levonorgestrel) the cytotoxic T-cells (CD8) were reduced and the CD4/CD8 ratio was increased significantly (p < 0,05).

Norgestimate. From the laboratory to three clinical indications.

This review of preclinical studies and clinical trials of efficacy and safety examines the relation between structure and function in the norgestimate (NGM) molecule, describes the pharmacologic characteristics of NGM and evaluates clinical experience with NGM in oral contraception (OC), treatment of hyperandrogenism in women and hormonal replacement therapy (HRT). NGM is a progestin of the 19-norsteroid series with an oxime group on C-3. In women, only low serum levels of NGM can be detected for five hours after ingestion. NGM is swiftly converted into its main metabolite, the 17-deacetylated norgestimate (norelgestromin), which carries the progestogenic properties of NGM. The metabolite reaches a mean peak concentration of 3,500 pg/mL 1.5 hours after intake and has a half-life of > 24 hours. The progestogenic potency of NGM and its main metabolite is comparable to that of progesterone. The doses of NGM in OCs effectively inhibit ovulation and control uterine bleeding. In the triphasic NGM/ethinyl estradiol (EE) OC, the total monthly load of progestin is only 4.5 mg. NGM has a low androgenic impact and does not interfere with the positive metabolic actions of estrogens, notably the estrogen-induced increase in high-density lipoprotein levels. OCs with NGM and EE increase the serum concentration of sex hormone binding globulin threefold, augmenting the binding of circulating testosterone and reducing free testosterone levels by 50%. Consequently, OCs with NGM are therapeutic for hyperandrogenic symptoms, such as acne. In a new type of HRT three-day dosing with 17 beta-estradiol (E2) alone is followed by three-day dosing with E2 plus NGM. This regimen treats vasomotor symptoms, protects the endometrium from hyperproliferation and is associated with a favorable lipid profile. NGM is a versatile progestin suitable for medical use from adolescence through the reproductive years to menopause.

Contraceptive and therapeutic effectiveness of two low-dose ethinylestradiol and cyproterone acetate regimens in the treatment of hirsute patients.

OBJECTIVE: To compare the effectiveness of two very low-dose ethinylestradiol and cyproterone acetate regimens in the treatment of hirsutism. PATIENTS: Eighteen hirsute women were randomized into two different regimens of cyproterone acetate and ethinylestradiol in a reverse sequential pattern: group 1 (0.28 mg ethinylestradiol monthly), group 2 (0.32 mg ethinylestradiol monthly). Both groups received 12.5 mg/day cyproterone acetate for the first 10 days of treatment each month. MAIN OUTCOME MEASURES: Hirsutism scores were measured according to the Ferriman and Gallwey scoring system and side-effects and complications were recorded during the 6 months of therapy. Ovulation was monitored by radioimmunoassay of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and progesterone levels. The pituitary response was studied using a gonadotropin releasing hormone test. RESULTS: Hirsutism scores decreased significantly in both groups at the end of the 6 months (-30%). All patients were anovulatory, as documented by the reduction of the LH, FSH, estradiol and progesterone levels. Pretreatment basal LH and FSH levels were higher than LH and FSH levels during the treatment. Side-effects were observed only occasionally with some differences between the two therapeutic regiments. CONCLUSION: Both treatments greatly improve hirsutism, reduce clinical problems and side-effects, guarantee both anovulation and contraceptive effectiveness and afford an optimal control of the menstrual cycle.

Advances in oral hormonal contraception.

PIP: Researchers continue to search for newer oral contraceptive (OC) formulations that retain the pill's beneficial effects while minimizing side effects. Changes in the clinical profile of OCs since their introduction in 1960 have enhanced their safety and acceptability. Most notable has been a trend toward the reduction of the pill's estrogen dose to 15-20 mcg of ethinyl estradiol and the consequent decline in cardiovascular risks attributable to thromboembolic processes. In addition, research has been directed toward the identification of selective gonane progestins that do not have the same atherogenetic impact as their predecessors. The low-dose gonane progestins may provide protection against cardiovascular disease through their beneficial impact on lipid profile. New regimes currently under study include a 23-24-day/month use pattern to reduce follicular ripening, use of estradiol rather than ethinyl estradiol, and the identification of progestins with special anti-androgenic effects. Also under investigation is the contraceptive potential of antiprogestogens such as RU-486. At present, the non-contraceptive benefits of OC use include reductions in ovarian and endometrial cancer, fewer ovarian cysts, less benign breast disease, a lower incidence of pelvic inflammatory disease, and less menorrhagia.^ieng

Oral contraceptives in premenstrual syndrome: a randomized comparison of triphasic and monophasic preparations.

Thirty-seven women with cyclical mood changes, either only in the premenstrual phase ('pure PMS') or during the entire cycle with premenstrual aggravation ('PMA'), were recruited to participate in a randomized study investigating the effect of three different oral contraceptives (OCs) on mood symptoms; 32 out of the 37 women completed the study. The monophasic ethinylestradiol (EE)/desogestrel (DSG) OC was compared, in a single (doctor)-blind cross-over design, with a monophasic and a triphasic levonorgestrel (LNG)-containing combined OC. The women kept a record of their symptoms and complaints by noting daily ratings using a validated visual analogue scale. One pretreatment cycle was followed by four treatment cycles, two cycles on each OC. All OCs had a beneficial effect on the PMS symptoms compared to the pre-treatment period. There were no changes between consecutive cycles. Cyclical symptom changes were noted during all OC treatment. The monophasic desogestrel pill provoked less changes in mood parameters than the monophasic and triphasic levonorgestrel OCs. However, physical complaints were less frequently reported during the use of the triphasic preparation as compared to the monophasic desogestrel preparation. Women with 'pure' PMS (premenstrual syndrome) were more consistent in their reactions on OCs compared to women with PMA.

[Hormonal contraception using estroprogestins]. / La contraccezione ormonale mediante estroprogestinici.

Today the estroprogestagen pill is the most valid method of contraception given that its benefits far outweigh its risks. The paper stresses the importance of a thorough anamnestic, clinical and laboratory examination so as to obtain correct and safe steroid contraception. The efficacy and excellent tolerance of the combined method currently make it the most widespread form of oral contraception.

PIP: Oral contraceptive (OCs) of high efficacy containing estroprogestins (EP) were introduced in the 1960's and since then more than 250 million used them. Their benefits include regular menstrual cycles and protection against genital tumors. Dosage seems to be directly related to risks and benefits, therefore new types of low-dose progestins have been developed. Their mechanism of action is based on hypothalamic- hypophysic control, EP suppress the production of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). Their effects are as follows: the cervical mucus becomes more viscous providing a barrier against spermatozoa, regressive (atrophy) modifications and proliferative alterations of the endometrium, and metrorrhagia induced by estrogens and amenorrhea provoked by progestins. The sequential pill requires administration of estrogens in the 1st phase and estroprogestins in the 2nd phase. They minimize physiological and hormonal effects, but the failure rate is 2-3% per woman year. Combined methods of monophasic, biphasic, and triphasic design are used from the 1st to 5th day of menstruation. They block ovulation with a high degree of efficacy, but the stimulating action of EP on the endometrium produces spotting, premature or late metrorrhagia, and amenorrhea. OCs protect against malignant epithelial tumors of the ovaries. It is estimated that 1700 ovarian carcinomas and 2000 endometrial carcinomas are averted each year by the use of the pill in the US. Endometrial cancer risk is halved by EP. 7 epidemiological studies have found no association between the pill and breast cancer, and the risk of benign mammary lesions is also reduced. Accurate anamnesis is mandatory for prescribing safe OCs including screening for coagulation, hepatic function and glycemia tests, and colposcopic examination. Smoking and the pill as well as age under 16 and over 36 increase risks. Nonetheless, the benefits of EP contraceptives outweigh the risks.

The effect of oral contraceptives on hormone profiles of oligomenorrheic adolescent cycles.

Nineteen adolescent girls with oligomenorrhea were studied to evaluate the effect of oral contraceptives (OCs) on hormone profiles, and 19 adolescent girls with regular menstruations served as control subjects. Serum levels of luteinizing hormone and androgens were higher in the oligomenorrheic girls than in the regularly menstruating girls. During the OC treatment the hormone levels of the oligomenorrheic girls decreased, approaching those of the control subjects. During follow-up cycle immediately after stopping the OCs the hormone levels increased rapidly, but in the oligomenorrheic girls the levels of luteinizing hormone, androstenedione, total and free testosterone were still significantly lower at the end of the post-treatment cycle than during the luteal phase of the pre-treatment cycle. The frequency of ovulation decreased to the same magnitude as reported in adults after discontinuation of OCs. No post-pill amenorrhea existed in either group of adolescents.

[Comparison of a 2-phase preparation (Oviol 22) with a low-dose 1-phase preparation (Ovoresta M)]. / Vergleich eines Zweiphasenpräparates (Oviol 22) mit einem niedrig dosierten Einphasenpräparat (Ovoresta M).

Oviol 22 was administered to 145, and Ovoresta M to 118 healthy female volunteers. During the first six cycles, 27 (18.6%) women discontinued the Oviol 22 intake, and 45 (38,1%) women discontinued the Ovoresta M intake. The other women were observed over 6 cycles. Together, 1,369 cycles were evaluated. Overall, the clinical results with Oviol 22 were more favourable than those with Ovoresta M. The discontinuation rate because of nausea, headache, acne and breast tenderness was lower in the group of women who received Oviol 22 than in the group of women receiving Ovoresta M. Cycle control was much better with Oviol 22 than with Ovoresta M. Following the administration of both preparations, no significant alteration in blood pressure, weight or mental status was seen. None of the patients became pregnant during the period of observation.

Oestrogens and endometrial cancer: a point of view.

The medical profession has been disturbed and bewildered by a number of recent communications which discussed a possible relationship between contraceptive sequential therapy and the incidence of endometrial cancer and between the postmenopausal application of conjugated oestrogens and endometrial carcinoma. An analysis of these reports is made critically and in detail and supplemented with observations on the risk of carcinoma of the breast. The practical aspects are delineated and a precise guide to postmenopausal oestrogen therapy presented.

[Current status of gestagen administration. 2. Gestagen therapy in the area of reproduction]. / Zum aktuellen Stand der Anwendung von Gestagenen. 2. Gestagen-Therapie auf dem Gebiet der Reproduktion

The spectrum of progestin therapy has changed and expanded during the last few years. 1. The drug-therapy of choice in endometriosis is the medication of progestins for at least six months, for instance ethinyl-testosterone. If a patient wants additional children the "more gentle" dydrogesterone should be considered. 2. In the treatment of dysmenorrhea combination pills should be given, sequentials should be avoided. In the case of incompatibility of estrogens or in danger of oversuppression syndrome dydrogesterone should be applicated. 3. Dysfunctional bleedings should lead to an intense search for their cause. The treatment consists in an estrogen-progestin combination for 9 days and in cyclic continuation of this therapy for at least a further three months. In the case of hemorrhagic diathesis progestin treatment should be continued. 4. Cyclic adequate progestins have proofed to be successful in handling of hirsutism. The choice of the preparation depends on the patient's wish for children. 5. The progestin test is still the first step in diagnosis of amenorrhea. 6. Progestin therapy is indicated in progressive endometrial carcinoma. Some medical centres treat carcinoma of the mamma successfully with progestins. 7. Nowadays fast and early hormonal pregnancy tests are available. The progestin-pregnancy-test is limited to cases of premenopause. 8. The so-called short luteum phase has received considerable attention as a possible cause of infertility. In these cases a substitutional therapy of progestins should follow. Clomiphene or HCG-therapy is advisable. In short luteum phase and premenstrual spottings potent progestins should be given. 9. High dosage of progestins are in common use in the treatment of abortus imminens. 10. Combination pills and sequentials are widely used, the possible methods of a pure progestin contraception are: minipills, three-month-injections, implanted silastic capsules with progestional compounds, progestin impregnated intrauterine devices, vaginal silastic rings impregnated with progestional compounds. 11. Carcinogenesis of progestins was not detectable. 12. Some progestins are teratogenic.

Clinical investigation of the biological effects of a new combination low-dose oral contraceptive ('Ovostat E').

PIP: A low-dose contraceptive containing 1 mg of lynestrenol and .05 mg of ethinyl estradiol was studied over 12 cycles in 11 healthy fertile women volunteers. The subjects were aged 20-30 years. Measurements were taken of urinary luteinizing hormone (LH), pregnanediol, and estrogen, and serum progesterone and estradiol values; in addition, on a fixed schedule during treatment, the 3rd, 5th, 7th, and 12th months, vaginal smears and endometrial biopsies were taken, along with SGOT and SGPT determinations. According to determinations, ovulation was inhibited during every cycle tested. A clear estrogenic effect was evident in the karyopyknotic index, during cycle 3, at the beginning of the cycle which became a progestational effect around Day 13 (biphasic). In cycle 6, the indexes of cytology decreased, but during Cycle 12, they rose a bit again. Basal body temperature during treatment was monophasic. Cervical mucus assessed by spinnbarket during treatment was low and arborization absent. The SGOT and SGPT liver function tests were within normal values in all cycles in 7 women; 4 showed clearly higher levels in Cycles 3 and 12. None of the cycles showed the high midcycle urinary excretion of LH. No significant side effects were reported. Examination of the endometrial biopsies showed a drug effect in all cases and there was no secretory activity in any of the samples. These findings confirm clinical results that show this low-dose combination to be an effective contraceptive agent.^ieng