Search

Study Objective As the experience of Transvaginal Natural Orifice Transluminal Endoscopic Surgery (vNOTES) has been accumulating, it has been questioned whether it can serve as an alternative approach for laparoscopic salphingo-oopherectomy for BRCA mutation carrier women, due to challenging accessibility and perhaps limited visualization of the abdominal cavity. The aim of this study is to report preliminary results using the vNOTES approach for risk reducing bilateral salphingo-oopherectomy for BRCA carrier women. Design A retrospective cohort study, February 2019 to January 2021. Setting Single medical center. Patients or Participants BRCA mutation carrier women that underwent risk reducing bilateral salphingo-oopherectomy via vNOTES approach. Interventions Data were collected from women's' medical files including demographics, medical and obstetrical history, operative characteristics and pathology results. All operations were performed by a single high skilled surgeon. Primary outcome was defined as successful bilateral salpingo-oopherectomy removal by vNOTES approach. Measurements and Main Results Thirty-seven women met inclusion criteria. Of them, 43% (n=16) and 57% (n=21) BRCA1 and BRCA2 mutations carriers, respectively, and 8% (n=3) both mutations carriers. Median age conducting risk reducing operation was 41(IQR39-54) years. Median parity was 2(2-3) with none of the women having past cesarean deliveries. All operations were completed using the vNOTES approach only. Diaphragmatic screening was reported normal in all of the women. No complications were documented in any of the operations including: Bleeding, damage to adjacent organ and need to transfer to laparoscopy. Operation median time was 60(57-68) minutes. All women were released from hospitalization the following day of the surgery. On follow up visit a month post operation, only one woman reported withdrawal bleeding, and all others reported being satisfied from the operation. Histo-pathological examination were clear in all of the women. Conclusion Risk reducing bilateral salphingo-oopherectomy by vNOTES provides a feasible new approach for the treatment of BRCA mutation carriers, with improved women comfort and better cosmetic results.

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.

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.

Between 1988 and 1992, a randomized phase III clinical trial was conducted in China to compare three monthly injectable contraceptives: Mesigyna, Cyclofem and Injectable No.1. This paper presents a detailed analysis of the menstrual diaries provided by 5098 (89%) of the subjects. In total, 902, 903 and 913 diaries were analyzed to compare bleeding patterns induced by Mesigyna, Cyclofem and Injectable No.1. The first withdrawal bleeding usually occurs 14–20 days after the first injection for all three of these preparations. Thereafter, 50% of Mesigyna users had precisely 3 bleeding/spotting episodes every 90 days, 50% of Cyclofem users had 2–3 and 50% of Injectable No.1 users had 3–4 episodes every 90 days. Relative to users of Mesigyna or Cyclofem, Injectable No. 1 users had 2–3 more bleeding/spotting days, and a shorter length of bleeding/spotting-free intervals in each period. 63.7%, 41.4% and 60.6% of subjects using Mesigyna, Cyclofem and Injectable No.1, respectively, had bleeding patterns similar to their untreated patterns in the first 90-day period. The percentages increased to 82.2% 67.8% and 75.0% in the fourth 90-day period. A total of 1815 diaries for Mesigyna and 1802 for Cyclofem were analyzed for more in depth comparison of these two methods. The number of bleeding/spotting days over four periods showed little difference between the two groups, but there were more spotting days and there was greater individual variability among Cyclofem users. Irregular bleeding in the first three months was 21.1% for Mesigyna and 26.1% for Cyclofem, decreasing to 4.4% and 7.7%, respectively, in the last three months of the treatment year. For Chinese women, Mesigyna provided better cycle control and more acceptable bleeding patterns than either Cyclofem or Injectable No.1.

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.

A postmenopausal woman, receiving cyclic hormonal therapy, presented to our clinic with acute pelvic pain, absence of withdrawal bleeding and clinical signs of vagal stimulation (nausea and vomiting). Vaginal exploration and ultrasonographic imaging accounted for haematocervix, which was confirmed by surgical blood evacuation.

Objective: To determine the response to the progestin challenge test on endometrial thickness 40 UI/ml and Estradiol

Human menopausal gonadotropin (HMG) was given to 10 patients who failed to ovulate after treatment with clomiphene citrate. Prior to one or more treatment courses, 200 mg. of clomiphene were administered daily for 5 days; at least one other treatment course was not preceded by clomiphene. Before therapy, progesterone in oil was administered and serum FSH, LH, and estrogen were measured. Those patients who had normal serum FSH levels and had withdrawal bleeding following progesterone had a reduction in amount and duration of HMG therapy when pretreated with clomiphene. There was no alteration in HMG requirements for those patients with low serum FSH who did not withdraw. Thus, sequential clomiphene-HMG therapy is of benefit only for those women with normal serum FSH levels and is the treatment of choice.

A SilasticR intravaginal ring (IVR) containing R2323 (17α-ethinyl-l7β -hydroxy-18-methyl-4,9,11-estrien-3-one) in its center core was tested in vitro and in four women for one cycle each. Initially 330 micrograms of drug was released per day from the IVR in vitro , and after 150 days the value had declined to about 230 micrograms. Ovulation was inhibited in the four subjects due to the constant release of R2323 as evidenced by the steroid blood levels of 1 to 3 ng/ml. When the IVR was removed, R2323 blood levels quickly fell to zero. All the women had normal withdrawal bleeding, and two subjects followed during a recovery cycle had ovulatory levels of progesterone.

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.

1. 1. Zuckerman's experimental data on the production of artificial menstrual cycles and a fluctuating uterine threshold to estrone in the monkey are reviewed. 2. 2. Artificial menstrual cycles (diethylstilbestrol withdrawal bleeding) were induced by cyclical diethylstilbestrol therapy in 4 patients with primary amenorrhea and in 4 postmenopausal women. 3. 3. Forty-two milligrams were found to be an optimum oral dose of diethylstilbestrol which in fourteen days would produce a normal degree of endometrial proliferation and would be followed by uterine bleeding. 4. 4. Seventy milligrams of diethylstilbestrol by mouth in fourteen days produced a slight degree of cystic glandular hyperplasia of the endometrium. 5. 5. The consistency of the latent interval that precedes withdrawal bleeding in the group of primary and postmenopausal amenorrheic patients, regardless of variation in dosage and manner of administration, leads one to believe that a fluctuating uterine threshold to estrogen may not be a factor with which to be concerned as it will be shown to be in patients with uterine bleeding (Palmer2), and as it is known to be in the ovariectomized monkey.

1.1. Progesterone has been given in various forms as 278 courses of treatment in seventy-six patients. 2.2. Antibleeding effects during metrorrhagia and withdrawal bleeding effects have been utilized in controlling metrorrhagia and amenorrhea. 3.3. Of eight patients with puberty metrorrhagia, four were apparently cured, one had recurrence after six months, and one developed amenorrhea. Two were not cured, being controlled only as long as progesterone was given. 4.4. Of thirty cases with metrorrhagia after puberty, thirteen were considered cured (seven received thyroid). 5.5. Of seven patients with primary amenorrhea, one was cured. This patient had an estrogenic vaginal mucosa before treatment and probably had only delayed menarche. 6.6. Of thirty-one patients with secondary amenorrhea, eight have been considered improved or cured (five received thyroid). 7.7. Progesterone produces a menstruating type of endometrium with fragmentation and necrosis, which apparently clears the uterus of the superficial layers of endometrium. 8.8. This useful procedure controls bleeding accurately, but cure apparently depends on spontaneous reversion to normal, aided in some cases by correction of abnormal weight changes, and the administration of thyroid as indicated.

1. 1. A method of approach to evaluation of the amenorrheic patient with emphasis on the importance of thinking in terms of physiologic processes in arriving at a differential diagnosis of cause is presented. 2. 2. General measures, indications for therapy, and specific hormonal therapy which has been successfully employed in functional amenorrhea are discussed. 3. 3. Results of clinical observations in 328 courses of therapy administered to 123 patients with functional amenorrhea employing either (a) anhydro-hydroxyprogesterone—10 mg., (b) progesterone—30 mg., or (c) a combination of estrogenic substances—1 mg. and progesterone—30 mg., by ingestion, three times daily for 5 consecutive days are compared. These preparations were found to be equally effective by ingestion in the dosage used, and withdrawal bleeding followed therapy in (a) 90.9 per cent, (b) 90.45 per cent, and (c) 94.1 per cent of instances. 4. 4. Simultaneous oral administration of estrogen and progesterone proved slightly superior to progesterone alone but was not sufficient in the dosage used to take the place of estrogen priming in those patients with inadequate intrinsic estrogens. 5. 5. It is believed that best results in management of functional amenorrhea are obtained by cyclic administration of estrogen and progesterone in a manner which closely simulates the normal physiologic process of the ovulatory cycle.

The estrogenic effect of estriol was studied in humans through the observation of vaginal cytology, ferning of the cervical mucus, estrogen withdrawal bleedings, progestin withdrawal bleeding, and endometrial stimulation. The findings indicate that estriol possesses a low order of estrogenicity at 1 mg. a day. The relative efficacy of estriol is less than 10 per cent of stilbestrol. Specific polarity of estrogenic response in the human reproductive tract could not be demonstrated.

Endogenous estrogen levels and progesterone withdrawal bleeding are useful in predicting the response to clomiphene citrate in ovulation induction in patients with secondary amenorrhea. In an attempt to correlate the two, 20 women with secondary amenorrhea had 24 hour urinary estrogen assays performed before administration of 17α-hydroxyprogesterone caproate. In 8 women, with estrogen levels above 11 μg bleeding occurred but did not in 5 with levels below 8 μg; between 8 and 11 μg the response was unpredictable. There was no correlation between estrogen levels and duration of amenorrhea or to the interval between progestogen administration and bleeding.

The effects of mixed synthetic estrogens ∗ ∗The following formula is the one used: was studied for the past four years in a group of 105 cases of menopause. The following results were obtained: 1.1. Freedom of symptoms for approximately four months. 2.2. No toxic reactions. 3.3. Three cases of withdrawal bleeding. 4.4. Synergistic action between the dimethoxy stilbestrol and stilbestrol.

2 oral progestogens: 6-alpha-methyl-17-hydroxyprogesterone acetate alone (oragest) and with added ethinyl estradiol (nogest); and 17-alpha-ethinyl-17-hydroxy-5(10)-estren-3-one with added ethinyl-estradiol-3-methyl-ether (Enavid); were used in 86 women for inhibition of lactogenesis. The progestogen-estrogen combinations proved to be most effective. Enavid appeared to inhibit lactogenesis most strongly. Nogest seemed to be almost as potent while the pure progestogen Oragest was definitely inferior. Ethinyl-estradiol used at .3mg as a control in this trial effectively prevented engorgement and breast pain but did not prevent lactogenesis. In the patients with 2 weeks follow-up no rebound or withdrawal bleeding was observed. Persistent lochia rubra were reported by about a third of these patients.