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ObjectiveTo evaluate serum estradiol (E2) concentrations during use of 90-day contraceptive vaginal rings releasing E2 75, 100, or 200mcg/day and segesterone acetate (SA) 200mcg/day to identify a dose that avoids hypoestrogenism.Study designWe conducted a multicenter dose-finding study in healthy, reproductive-aged women with regular cycles with sequential enrollment to increasing E2 dose groups. We evaluated serum E2 concentrations twice weekly for the primary outcome of median E2 concentrations throughout initial 30-day use (target ≥40pg/mL). In an optional 2-cycle extension substudy, we randomized participants to 2- or 4-day ring-free intervals per 30-day cycle to evaluate bleeding and spotting based on daily diary information.ResultsSixty-five participants enrolled in E2 75 (n=22), 100 (n=21), and 200 (n=22)mcg/day groups; 35 participated in the substudy. Median serum E2 concentrations in 75 and 100mcg/day groups were 40pg/mL throughout 30days; E2 concentrations were 37pg/mL (range 28-62pg/mL) on days 88-90 (n=11). Among the E2 200mcg/day substudy participants, all had withdrawal bleeding following ring removal. The 2-day ring-free interval group reported zero median unscheduled bleeding and two (range 0-16) and three (range 0-19) unscheduled spotting days in extension cycles 1 and 2, respectively. The 4-day ring-free interval group reported zero median unscheduled bleeding or spotting days.ConclusionsEstradiol concentrations with rings releasing E2 200mcg/day and SA 200mcg/day avoid hypoestrogenism over 30-day use.ImplicationsA 90-day contraceptive vaginal ring releasing estradiol 200mcg/day and segesterone acetate 200mcg/day achieves estradiol concentrations that should avoid hypoestrogenism and effectively suppresses ovulation.

Objectives: To facilitate embryo transfer technique in cases with previous failed or difficult transfer using office hysteroscopy. Study Design: Case report of 3 cases of previous difficult embryo transfer (ET). Methods: Hysteroscopic assisted insertion of cervical stent at the end of withdrawal bleeding in the stimulation cycle. This stent was used as a track for embryo transfer catheter. Results: One case cancelled before (embryo transfer) ET and the other 2 cases didn’t get pregnant in spite of easy embryo transfer. Conclusion: This hysteroscopic assisted ET technique may facilitate ET technique in cases with difficult embryo transfer due to deformed cervix.

Article, 信州医学雑誌 63(4):215-223 (2015)

Se estudia los efectos farmacológicos del compuesto RH 2267, fármaco de capacidad progestacional, sobre los órganos finales del aparato genital femenino. El efecto progestacional se encontró a las dosis de 230-500-75 y 1000 mcgrs. A dosis mayores, induce la hemorragia por supresión.

Objective To compare two protocols of CC therapy for induction of ovulation in a group CC resistant PCOS women. Study design Double blind randomized controlled trial. Subjects and methods 260 nulliparous CC resistant PCOS women randomized between two groups; In the first group each patient received 200 mg/day for 5 days while the second group received 100 mg/day for 10 days, both starting on day 3 of progestin induced withdrawal bleeding. Main outcome measures Ovulation defined as at least one follicle reaching ⩾14 mm diameter, and confirmed by timed serum progesterone. Secondary outcome measures included; number of dominant follicles, endometrial thickness, clinical pregnancy rate, and live birth rate. Results The extended protocol resulted in significantly higher ovulation, pregnancy, and live-birth rates than the high dose protocol ( p 0.001). Serum FSH levels on day 6 of treatment were comparable between the two groups while the level on day 11 was significantly higher in the second group ( p 0.02). Serum LH levels were comparable both on days 6 and 11. Patients on longer protocol (group II) required a longer time to ovulate (18 ± 4.4 versus 14 ± 3.6 days) but had a significantly higher endometrial thickness at the time of ovulation. ( p 0.02) FSH and LH levels were comparable between responders and non-responders in both groups. Conclusions The current study reports significantly higher ovulation and pregnancy rates with the longer lower dose protocol probably because of prolonged FSH rise. Study web address: ACTRN12611000639921.

The aim of this study was to compare the efficacy of a merocel technique with conventional nasal packing, in the classic septuplasty operation. The study is a prospective, randomized clinical trial. 60 patients underwent septuplasty for septal deviation and ensuing nasal obstruction. These patients were divided into two groups: conventional gauze packing and merocel packing. Randomization was performed using the two block randomization system. Patients who failed the regular follow-up were excluded, and the two groups were compared for postoperative bleeding, pain, hematoma, and adhesions. Patients were asked to record pain levels using a visual analogue scale. The authors found significant statistical differences between the two groups in the parameters studied, but significantly higher pain levels, Adhesions and withdrawal bleeding were noted in the patients in the gauze packing group. The final results confirmed that patients who underwent septuplasty with merocel packing had more smooth post-op recovery with less complication then conventional gauze packing.

Two 54-year-old women developed abdominal cramps and vaginal hemorrhage as a result of endometrial hyperplasia during treatment with a hop-containing phytotherapeutic product (MenoCool®) for post-menopausal complaints. The women used the hop-containing phytotherapeutic product (418 mg of hop per tablet) twice daily (1 and 0.5 tablets by both patient A and B). Patient A developed abdominal cramps and vaginal hemorrhage after 2 months of use. After gynecological examination, she was diagnosed with endometrial hyperplasia. The patient was treated with a curettage. The hop-containing phytotherapeutic product was discontinued, and the patient recovered. Patient B developed abdominal pain/cramps and vaginal hemorrhage after 5 months of use. A cervix smear, internal examination, and ultrasound were performed. Due to the thickness of the endometrium, a pipelle endometrial biopsy was performed. Results showed no indication for cervix cancer. The use of MenoCool® was ceased; follow-up information received from the patient shortly thereafter indicated that she had almost entirely recovered from the abdominal pain/cramps and vaginal hemorrhage. Hop (Humulus lupulus) has phytoestrogenic properties that may be the cause of endometrial hyperplasia and subsequent vaginal hemorrhage. A Naranjo assessment score of 5 was obtained for both cases, indicating a probable relationship between the patient’s endometrial proliferation and subsequent vaginal hemorrhage and their use of the suspect drug.

Objective: Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. Design: This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. Methods: Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH ≥7 IU/l, advanced bone age >1 year, enlarged uterus (≥36 mm) and testosterone level ≥0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. Results: GnRH-stimulated peak LH ≤3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. Conclusions: The triptorelin 3-month depot efficiently suppresses the pituitary–gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.

Objective: to review the potentid applications of photodynamic therapy (PDT) in gynaecology, using 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photosensitization. Methods: relevant publications were retrieved by searches on Medline between 1986 and 1996 using the following MeSH headings: 5-aminolevulinic acid, photofrin, haematoporphyrin derivative, endometrium, photodynamic therapy or using a combination of the above. References were also obtained from reference lists of known sources. Results: photodynamic therapy using ALA appears to offer the potentid of a simple, non-surgical approach to ablation of the endometrium. Its application as an office procedure would provide a major advance for women suffering from menorrhagia, and could eliminate the unwanted withdrawal bleeding experienced by post-menopausal women on hormone replacement therapy (HRT). Photodynamic therapy could be used to treat ectopic pregnancies in cases where laparoscopy is needed for diagnosis, and has the potentid for the detection and treatment of endometriosis. Photodynamic therapy has been employed for palliative treatment of advanced gynaecologic alignancies and may play a role in treating benign vulvar and vaginal lesions, for example, condylomata. Conclusions: 5-aminolevulinic acid-induced PpIX photosensitization has the potentid to play a significant role ingynaecology due to its specificity for desired target tissues in the pelvis. The major clinical applications of ALA-PDT are likely to be the ablation of the endometrium in women suffering from menorrhagia and the simplification of HRT in post-menopausal women.

Swyer syndrome also known as 46XY complete gonadal dysgenesis is a rare cause of primary amenorrhea. These patients are phenotypically females with female type of internal and external genitalia with absence of testicular tissues. They have streak gonads which have increased potential to turn into malignancy. Bilateral gonadectomy should be done as soon as diagnosis is made. In present case, 20 years unmarried female came with complaints of menstrual bleeding only on taking medication. She never attained menarche, following which she was started on treatment outside, on withdrawal bleeding for the past 3 years. She was now evaluated and diagnosed as Swyer syndrome and bilateral gonadectomy was done laproscopically. Swyer syndrome patients can get married, have normal sexual life and can get pregnant through invitro fertilisation with donor oocyte if desired.

The practice of extending combined oral contraceptive use (COC) and eliminating or reducing the hormone free interval has been in use for many years. More recently a range of products with new dosing options has been developed and marketed. Women and physicians in developed countries are comfortable with and many prefer the use of extended COC regimens which provide an option to eliminate or reduce the frequency of regular withdrawal bleeding. The extension of active pill taking and the reduction or elimination of the hormone-free interval have been shown to be beneficial for women who experience menstrual cycle-related problems such as heavy bleeding or dysmenorrhoea. The hormone-free interval of less than seven days has additional benefits in managing hormone withdrawal symptoms and efficacy may be improved in situations where pills are inadvertently missed or in women who are perceived as 'poor' pill takers. This paper provides a descriptive review highlighting the development of new dosing options that alter the traditional 21/7 COC regimen. The rationale for and the acceptability of COCs developed with alternative dosing regimens is examined.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:24:47Z No. of bitstreams: 0 Made available in DSpace on 2014-05-27T11:24:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-09-01 We report on the results of a double-blind, randomized, controlled clinical trial comparing two preparations of ethinylestradiol and cyproterone acetate in the treatment of women of reproductive age presenting menstrual irregularities of hyper-androgenic origin. After obtaining informed consent, subjects were randomized to a 4-month treatment period consisting of one daily dose of 0.035mg ethinylestradiol + 2mg cyproterone acetate. The treatment regimen cycle consisted of one pill, once daily for 21 days, followed by a 7-day pill-free period. We compared the efficacy of two presentations of the drug combination after each treatment cycle (Visits 2, 3, 4, and 5) in establishment and maintenance of menstrual regulation, intensity of menstrual flow, and dysmenorrhea, as well as a comparison of the two presentations in terms of Global Satisfaction and Drug Satisfaction assessments performed by the patients and the investigating physician. At each study visit, drug compliance and use of concomitant medications, as well as incidence, severity and duration of adverse events were recorded. A total of 86 subjects were randomized to treatment, with 43 subjects in each treatment group. At Visit 2 and each subsequent visit, all patients in both treatment groups reported an episode of withdrawal bleeding during the 7-day hormone-free period. We observed a statistically significant (p

Objective To compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects. Design Prospective, randomized, double-blind. Setting Academic institution. Participants: Out of 190 screened with oligomenorrhea/amenorrhea, 60 who qualified completed the study. Interventions A 10-day course of (1) oral micronized P 300mg, (2) oral micronized P 200mg, or (3) placebo. Main Outcome Measures Withdrawal bleeding, side effects, and changes in lipids. Endogenous estradiol (E 2 ) concentrations at baseline and P concentrations during treatment were correlated with bleeding response. Results Withdrawal bleeding occurred in 90% of women taking 300mg, 58% of women taking 200mg, and 29% of women taking placebo ( P P =not significant). Lipid concentrations were unchanged. Endogenous E 2 and treatment P concentrations were of limited predictive value for withdrawal bleeding. Conclusions Progesterone 300mg induced significantly more withdrawal bleeding than placebo, with similar side effects. Bleeding response cannot be predicted reliably from E 2 and P concentrations.

One hundred fifteen women under age 40 presenting with hypergonadotropic amenorrhea (follicle-stimulating hormone greater than 40 mIU/mL) were evaluated. Incomplete pubertal maturation and chromosomal abnormalities were more likely in the 18 women (15.7%) with primary amenorrhea than in those with secondary amenorrhea. The 97 women with secondary hypergonadotropic amenorrhea were significantly more apt to complain of symptoms of estrogen deficiency, have been pregnant before diagnosis, and have evidence of ovulation after diagnosis. Withdrawal bleeding occurred commonly (greater than 48%) in those women administered exogenous progestin. Immune abnormalities occurred with approximately equal frequency (17.4%), and spinal bone density was decreased in both groups.

Surgically menopausal women are 5 times more likely to begin hormone replacement therapy than are naturally menopausal women, and they continue therapy for longer periods. The primary reasons that women refuse hormone replacement are fear of cancer and perceived side effects. In contrast, withdrawal bleeding is the major reason that women discontinue hormone replacement therapy. Physician-patient communication plays an important role in a woman's decision to use hormone replacement therapy, to fill her prescription, and to adhere to the regimen. The first visit at which hormone replacement therapy is discussed is crucial to establishing an effective patient-physician relationship. At least 15 minutes, and preferably 45 minutes, should be reserved for this visit. Patient follow-up-either by phone or in person-during the first month can help improve adherence because this is when many women may have nuisance side effects and discontinue therapy.

Objective: To describe a technique for surgical management of complete obliteration of the endometrial cavity. Design: A report of a series of three patients. Setting: A university-based hospital. Patient(s): Three patients with complete obliteration of the endometrial cavity. Intervention(s): Transfundal scar removal using stents in the fallopian tubes to serve as landmarks. Main Outcome Measure(s): Regular withdrawal bleeding. Result(s): Regular menses in all three patients. Conclusion(s): The technique described here shows promise for establishing uterine cavity integrity in cases of complete endometrial obliteration where there are no landmarks in the uterine cavity.

Microperforate hymen is a congenital obstructive vaginal membrane with a tiny opening. It is usually detected long before menarche because of recurring vulvovaginitis and urinary tract infection. We report a case of microperforate hymen in a 27-year-old women presenting oligomenorrhea, in whom the location of the tiny opening on the hymenal membrane was detected by withdrawal bleeding without anesthesia, and definitively diagnosed preoperatively by using hysterofiberscopy.

One hundred and sixty-five women were treated during a total of 3,281 cycles with Neo-Lyndiol, a combined oral contraceptive containing 2·5 mg lynestrenol and 0·050 mg ethinyloestradiol per tablet. The tablets were taken for 32 days, with six tablet-free days. No pregnancies were seen and the proportion of patients experiencing irregular bleeding and side-effects was very low and in fact their complaints decreased considerably as medication continued. There was a drop-out rate of only 5·5%, which is exceptionally low. Neo-Lyndiol proved to be a reliable preparation, controlling the cycle well and causing few side-effects.

A multicentre clinical trial comparing a novel formulation (the Paper Pill) of a combined oral contraceptive containing 30 microgram ethinyloestradiol and 150 microgram levonorgestrel with a conventional tablet formulation (Microgynon 30) has been carried out in 336 women over 6 cycles. There were no pill failures in women taking either preparation with one exception in the Microgynon 30 group which was due to poor patient compliance. Cycle control judged by cycle length, duration and amount of withdrawal bleeding and the incidence of intermenstrual bleeding was good in both groups. The number of adverse effects was slightly less in the Paper Pill group and fewer withdrawals for questionnaire reasons were noted than in the Microgynon 30 group. A questionnaire showed that the Paper Pill was accepted well by the majority of women in the trial.A multicenter clinical study was conducted to assess the efficacy, cycle control, tolerance, and acceptability of the PP (paper pill) with conventional combined OCs (oral contraceptives), Microgynon 30 tablets. The study was conducted at 28 centers in Great Britain among 336 women for 6 cycles. There was only 1 failure, in a woman who admitted poor compliance. Cycle control as judged by cycle length, duration and amount of withdrawal bleeding and the incidence of intermenstrual bleeding was good for both the OC and the PP. Slightly more of the OC than the PP patients withdrew from the trial for medical and nonmedical reasons. The incidence of side effects was slightly less among the PP patients. The majority of PP users found that method easier or at least as easy to take as the conventional OC. The PP can, thus, provide an effective alternative for women whose allergic or religious restrictions interfere with normal OC intake. The small, lightweight pack provides an added advantage.

Thirty-two patients with stress amenorrhea of less than 1 year's duration were found to have withdrawal bleeding after progestin administration, normal serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, and good responsiveness to LH-releasing hormone (LH-RH); ovulation was induced following the administration of clomiphene citrate. On the other hand, in 11 of 14 patients with stress amenorrhea of longer than 1 year's duration, no bleeding followed the administration of progestin, and there were noted high serum FSH and LH levels, exaggerated release responsiveness to LH-RH, and atrophic vaginal smears and endometrium. In addition, it was difficult to induce ovulation by various treatments. The findings suggest thtat dysfunction in the hypothalamic cyclic (not tonic) center regulating ovulation was the originating factor in the amenorrhea in question and that ovulation should be induced at least once yearly to prevent ovarian function from declining in this type of anovulatory state existing for more than 1 year.

Twelve immature female monkeys were treated with varying amounts of pregnant mare's serum gonadotrophin (PMSG). Seven of these monkeys responded to PMSG treatment as shown by sex skin development, ovarian enlargement and withdrawal bleeding. These animals reached menarche between 23 and 26 months of age, almost 1 year earlier than untreated control monkeys. Five other animals did not show an initial response to PMSG treatment and attained puberty simultaneously with the untreated animals. It is suggested that increased production of oestrogen by the PMSG-stimulated ovaries may affect the hypothalamo-hypophysial axis in such a way that puberty is accelerated.

Psychological factors are the most common cause of menstrual dysfunction. Emotionally-induced disturbance at the hypothalamic level can lead to irregular cycles, dysfunctional uterine bleeding, or amenorrhea. Mild disturbances are usually associated with an ample amount of endometrial lining, and a period of withdrawal bleeding can usually be produced with progesterone. Where there is a deficiency of estrogen and consequently insufficient endometrial lining for withdrawal bleeding, organic pituitary and/or hypothalamic disease must be excluded. The psyche can also influence the uterus and ovary directly.

Results of 75 women with functional menstrual disorders treated wit h norethisterone (5-25 mg/day) during 349 menstrual cycles are presented . Norethisterone (10 mg or less/day for 4 days) induced withdrawal bleeding in 180 out of 182 occasions of metropathia hemorrhagia. 20 mg/day for 4 days then 10 mg/day for 7 days arrested metropathia bleeding and was followed by normal withdrawal bleeding in 5 out of 8 occasions. Normal bleeding occurred in 13 cases of ovulatory menorrhagia in 34 out of 52 cycles when norethisterone was administered from Cycle Day 15-25. Dysmenorrhea however was a common complaint. 27 patients with dysmenorrhea were relieved in 65 out of 91 occasions following norethisterone treatment before Cycle Day 6. Side effects were minimal.

Almost 5% of women is affected by irsutism and about 55% of these subjects start complaining on some signs during the adolescence period in which a considerable anxiety is connected with the body image. After having excluded Cushing's syndrome, CAH late onset, ovarian and adrenal turnours, we treated six adolescents (mean age 16yr 1mo)affected by hirsutism (Hatch's score ≥ 10) with 100 mg/daily of spironolactone for 12 months (200 mg/daily with score > 20 or therapeutical unsuccess after 6 months of therapy). To all subjects was added an oral contraceptive (0.15 mg of descgestrel + 0.03 mg of ethinil -estradiol) to obtain regular withdrawal bleeding and contraception effect. To make a correct evaluation of the data, we excluded from the study those areas treated by esthetic treatment. Clinical and hormonal evaluations (FSH, LH, PRL, T, DHEAs) were obtained before and after 3-6-9-12 months of therapy. During follow-up no change was demonstrated in hormone levels; the mean score significantly decreased after 3 months of therapy (p < 0.01) and at every specific control (p < 0.001). In one girl, 6 months off-therapy, no sign of hirsutism was demonstrated. No significant side-effects were noted in our patients. Spironolactone combined to an cstro-progestagen is an effective and well-tolerated approach to the smanagement of hirsutism in adolescents.

Hyperprolactinemia is recognized commonly as a cause of menstrual dysfunction and hypogonadism in adults but is often assumed to be rare in adolescents. The clinical features of this in adolescence have not been well characterized. We have studied 20 patients with adolescent onset of hyperprolactinemia. Initial results on 16 (13 females and 3 males) are as follows: The cause of hyperprolactinemia was microadenoma in 6, macroadenoma in 7, pituitary cyst in 1 and tumor hydrocephalus in 2. Onset was between 9 and 19 years with a mean of 14.6 years but the diagnosis was delayed almost 5 years to a mean age of 19.3 years. Prolacting levels varied from 33 to 3450 ng/ml. Presenting complaints in females were: Amenorrhea in 64%, galactorrhea in 18%, cystic acne in 9%. Galactorrhea was present in 73% but only 1/3 of these were aware of it. Headaches were present in 82%. 6 of 8 patients had withdrawal bleeding after Provera. 3 patterns of pubertal progression were seen: 1)primary amenorrhea 18%, 2)normal menarche with only a few periods 36%, 3) normal menarche, irregular menses for several years and amenorrhea in 46%. 4 of 5 patients with macroadenomas have had surgery, radiotherapy or both and 3 of these have residual hyperprolactinemia and other residua. Although hyperprolactinemia is a common cause of menstrual or pubertal disturbance in adolescence, diagnosis is usually delayed. Because outcome is often suboptimal, an effort toward timely diagnosis is indicated.

The inhibition of lactation by prescribing free fluid intake described by Mr. C.K. Vartan (4 January p. 50) is a most satisfactory method of suppression. The disadvantages of the stilboestrol method the secondary engorgement of the breasts and the withdrawal bleeding which sometimes occur are eliminated. It would appear now that the risk of venous thrombosis is greatly reduced. Free fluids have been used for a considerable time as the sole method of suppression of lactation in out maternity unit and we have found it most effective. Stilboestrol does not appear to have any superior advantage. I can recommend the free fluid technique to Dr. D.D. Brown (4 January p. 50) as a thoroughly satisfactory replacement for stilboestrol in the suppression of lactation. (Full text)