Somatic and reproductive development in pre-pubertal mice treated with cyclophosphamide and subsequent estrogen replacement.

We tested the hypothesis that chemotherapy would prevent the expected pubertal development of uterus, ovaries, and long bones, and that estrogen replacement subsequent to treatment with chemotherapy would restore uterine and bone development to expected sizes. Pre-pubertal female C57BL/6J mice (n = 78) were assigned to receive placebo (controls), 200 mg/kg (group A), or 120 mg/kg (group B) of cyclophosphamide (CTX) on postnatal day 18. Mice were subsequently randomized to receive estradiol placebo or long-release estradiol pellet insertion on day 22 (early estradiol dose), day 45 (mid estradiol dose), or day 67 (late estradiol dose) of life. Body weight and length, uterine and ovarian weight, and right femur length and weight were measured. Mice treated with CTX had shorter and lighter femurs and lighter ovaries than controls (13.46 cm ± 1.51 cm vs. 15.00 cm ± 1.10 cm, 57.70 mg ± 9.71 mg vs. 65.30 mg ± 3.68 mg, and 5.16 mg ± 3.00 mg vs. 10.05 mg ± 2.31 mg, respectively; p < 0.05). Mice receiving estrogen replacement had a larger average body weight, BMI, and uterine weight than those that received placebo estrogen (19.56 g ± 1.82 g vs. 18.10 g ± 2.08 g, 26.53 g/cm(2) ± 2.91 g/cm(2) vs. 23.47 g/cm(2) ± 3.06 g/cm(2), 101.19 mg ± 41.69 mg vs. 50.00 mg ± 9.49 mg, respectively; p < 0.05). Cyclophosphamide treatment in pre-pubertal mice negatively affected femur and reproductive development. Estrogen treatment restored expected uterine development by maturity, regardless of the timing of administration. However, there was no similar recovery of femur length and bone mass was only partially recovered.

Optimal pain management in total abdominal hysterectomy.

UNLABELLED: Effective postoperative pain management provides improved patient comfort and satisfaction, earlier mobilization, fewer pulmonary and cardiac complications, reduced risk of deep vein thrombosis, faster recovery, and reduced cost of care. Although many therapeutic modalities are available for pain management, the optimal combination in managing postoperative pain in total abdominal hysterectomy is controversial. The objective of this study was to review the literature to formulate optimal, evidence-based preoperative, intraoperative, and postoperative pain management for women undergoing total abdominal hysterectomy. Using the OVID platform, we searched in MEDLINE and PubMed using MeSH terms postoperative pain and total abdominal hysterectomy for published articles from 1960 to the present; we found 545 studies. We screened and included only randomized clinical trials, publications in English, human studies, and abdominal hysterectomy for noncancerous indications. We excluded 456 studies that reported on animal studies; laparoscopic, vaginal, supracervical, or robotic hysterectomy; pharmacokinetic studies; primary outcome other than pain management; and chronic pain management. Studies with inadequate power, poor methodology, or inconclusive results were further excluded from this review. Thus, 89 studies constituted the cohort for our article. Pain control remains complex given variables such as age, anxiety, and extent of surgery. In general, regimens should be tailored to the needs of the individual patient, taking into account medical, psychological, and physical condition. A multimodality approach is better than conventional, single-agent narcotic in achieving optimal pain management. After reading this article, the reader should be able to understand various modalities that can be considered for preoperative, intraoperative, and postoperative pain management in total abdominal hysterectomy. TARGET AUDIENCE: Obstetricians and gynecologists, family physicians Learning Objectives: After completing this CME activity, physicians should be better able to understand various modalities that can be considered for preoperative, intraoperative, and postoperative pain management in total abdominal hysterectomy.

GnRH-analogues for ovarian protection in childhood cancer patients: how adult hypotheses are relevant in prepubertal females.

Systemic chemotherapy frequently causes primary ovarian insufficiency. In prepubertal girls, currently the only option to preserve ovarian function is ovarian tissue preservation. The use of gonadotropin-releasing hormone analogues given in combination with chemotherapy has been studied in reproductive age women. The exact mechanism is unknown, but some of the proposed protective mechanisms could theoretically protect the prepubertal ovary as it has been theorized in many of the studies on reproductive age women. None of the studies implies an adverse affect of GnRH analogue administration in terms of worsening health or cancer status. As 83% of children diagnosed with cancer will survive into adulthood, GnRH analogue administration to female childhood cancer patients in combination with chemotherapy might represent a valuable attempt to preserve future ovarian function and fertility when ovarian tissue preservation is not an option.