Israel Medical Association Journal

Background: Systemic lupus erythematosus (SLE) is an autoimmune disease with multiorgan involvement and wide variability in presentation and course. Although it can appear at any age, women of childbearing age are primarily affected. This has led to the proposal of a hormonal role in the development of SLE. Among the main hormones shown to have immunomodulatory effects are estradiol, progesterone and prolactin.

Objectives: To report the levels of estradiol and prolactin in SLE patients and establish the relationship between these levels and disease activity, and to determine whether the phases of the menstrual cycle influence the activity of SLE and its relationship to hormone levels.

Methods: In this cross-sectional study, we examined 60 women with SLE. We measured disease activity using SLEDAI and BILAG. We obtained peripheral blood samples to determine the levels of estradiol, progesterone, and prolactin. 

Results: Patients’ age ranged between 16 and 65 years and the mean disease duration was 5.5 years (0–20). SLE was active (SLEDAI > 6) in 13 patients and inactive in 47. Thirty patients were in a pre-ovulatory menstrual cycle phase, 13 in a post-ovulatory cycle, and 17 were menopausal. We found a significant association between C4 levels and disease activity (P = 0.01) and between estradiol levels and disease activity in the kidney (P = 0.04). We did not find hyperprolactinemia in any patient. 

Conclusions: In this population, we found an association between estradiol levels and organ-specific activity in the kidney. One may speculate as to whether our population might benefit from the implementation of anti-estrogen therapy for control of disease activity, particularly in the kidney.

 

Background: Adjuvant/neoadjuvant chemotherapy in breast cancer patients may be associated with amenorrhea and a marked reduction in ovarian reserve.

Objectives: To assess the use of letrozole with follicle-stimulating hormone (FSH) in gonadotropin-releasing hormone (GnRH) analogue protocols, based on reported attempts to avoid the estradiol (E2) increase during controlled ovarian hyperstimulation for embryo cryopreservation in breast cancer patients using a combination of low dose FSH and aromatase inhibitor (letrozole) in a GnRH-antagonist protocol.

Methods: Twenty-four breast cancer patients were treated with recombinant FSH (150–450 U/day) and letrozole (5 mg/day) in a long GnRH-agonist (n=7) or GnRH-antagonist (n=17) protocol. After oocyte retrieval, insemination and/or intracytoplasmic sperm injection was performed. The embryos were frozen.

Results: The average interval from surgery to oocyte retrieval was 40 days. Average duration of treatment was 9.6 days and mean peak E2 level 1342 ± 1091 pmol/L, yielding 16.0 ± 16.3 oocytes (range 0–82). Mean fertilization rate was 69.5 ± 20.4% and mean number of embryos cryopreserved 10.3 ± 9.3. More oocytes were retrieved with the long GnRH protocol, but the difference was not statistically significant (24.8 ± 24.6 vs. 12.0 ± 8.8 pmol/L, P = 0.07).

Conclusions: As previously reported, ovarian stimulation with letrozole and FSH, in both the long GnRH-agonist and GnRH-antagonist protocols, is apparently effective in breast cancer patients and spares them exposure to high E2 levels.
 

Background: Continuous use of combined oral contraceptives is currently attracting growing interest as a means of improving menstrual related symptoms and reducing the number of bleeding days.

Objectives: To evaluate bleeding patterns, menstrual symptoms and quality of life with an extended 84/7 oral contraceptive regimen versus 21/7 cycles.

Methods: In two consecutive run-in cycles, 30 µg ethinyl estradiol and 3 mg drospirenone tablets taken on days 1–21 were followed by a tablet-free period from days 22 to 28 of each cycle and then by two 84 day cycles of pill use with a 7 day tablet-free interval. The primary outcome was the total number of bleeding/spotting days. Secondary outcomes were severity of daily symptoms, general well-being determined by the PGWBI questionnaire, and overall treatment satisfaction.

Results: Of the 137 women invited to participate in the study 109 (aged 18–40 years) were enrolled. The number of bleeding days decreased by about one-third from a calculated 31.8 days of bleeding under a cyclic 21/7 regimen to an expected total of 21.8 days for the extended 84/7 regimen. The incidence of menorrhagia, intermenstrual bleeding, dysmenorrhea, abdominal bloating, breast tenderness, depressive moods and irritability – when compared at enrollment and at the end of the second extended study period – was significantly lower (P < 0.005) among women on the continuous pill regimen. The median (range) global PGWBI scores were not substantially different before and after the extended use cycles: 78.2 (39.1–96.4) and 77.3 (30.9–96.4), respectively. Body weight and skin condition also remained constant. At the completion of the study: 65.5% of the women were either highly satisfied (41.4%) or satisfied (24.1%) with the extended regimen.

Conclusions: The extended 84/7 regimen was found to be satisfactory for the majority of participants and was associated with a decrease in the number of bleeding days and an improvement in menstrual symptoms compared to 21/7 cycles. 

Objectives: To assess the effect of a vaginal ring delivering estradiol and progesterone in postmenopausal women and to determine whether continuous administration can relieve climacteric symptoms, produce an acceptable pattern of vaginal bleeding and control endometrial proliferation.

Methods: Twenty-nine postmenopausal women with an intact uterus were studied. All had climacteric symptoms. The vaginal rings contained 0.36 g estradiol and either 3.6 g progesterone (high dose progesterone) or 1.8 g (low dose progesterone), and were kept in place for 4–6 months. Serum progesterone, estradiol and estrone were measured and endometrial thickness determined. All women kept a daily diary of bleeding/spotting and completed a questionnaire on climacteric symptoms at monthly intervals. The low dose progesterone group comprised 14 women and the high dose progesterone group 15 women.

Results: A total of 18 patients (9 in each group) completed the study. Mean levels of estradiol, estrone and progesterone were at their peak after 2 to 4 weeks. All rings were effective in alleviating vasomotor symptoms, although there was evidence of the "escape from effect" in month 6. Endometrial thickness increased in 6 of the 29 women but biopsy in each case showed no evidence of hyperplasia. Of the 18 women who completed the study, 5 had amenorrhea throughout, 7 had amenorrhea after 3 months, and the remainder had one or two bleeding episodes after 3 months. Therapy was discontinued in 11 women.

Conclusions: A vaginal ring delivering estradiol and progesterone controlled climacteric symptoms, prevented endometrial proliferation, and provided an acceptable bleeding pattern. It should be viewed as a promising alternative for short-term estrogen-progesterone therapy.

Background: Uterine rupture is a catastrophic obstetric complication, most often associated with a preexisting cesarean section scar. Although a vaginal birth after a cesarean is considered safe in modern obstetrics, it is not known whether repeated VBACs increase the risk of rupture, or whether the first VBAC proves the strength and durability of the scar, predicting further successful and less risky vaginal deliveries.

Objectives: To evaluate the effect of repeated vaginal deliveries on the risk of uterine rupture in women who have previously delivered by cesarean section.

Methods: In this retrospective study, 26 VBAC deliveries complicated by uterine rupture were matched for age, parity, and gravidity with 66 controls who achieved VBAC without rupture. The histories, demography, pregnancy, labor and delivery records, as well as neonatal outcome were compared.

Results: We found that the risk of rupture decreases dramatically in subsequent VBACs. Of the 40 cases of uterine rupture recorded during the 18 year study period, 26 occurred during VBAC deliveries. Of these, 21 were complicated first VBACs. We also found that the use of prostaglandin-estradiol, instrumental deliveries, and oxytocin had been used significantly more often during deliveries complicated with rupture than in VBAC controls.

Conclusions: Once a woman has achieved VBAC the risk of rupture falls dramatically. The use of oxytocin, PGE2 and instrumental deliveries are additional risk factors for rupture, therefore caution should be exerted regarding their application in the presence of a uterine scar, particularly in the first vaginal birth after cesarean.

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VBAC= vaginal birth after cesarean section

PGE2= prostaglandin-estradiol