James H. Liu

The Women's Health Initiative postmenopausal hormone trials: overview and baseline characteristics of participants.

The postmenopausal hormone therapy (PHT) component of the Women’s Health Initiative (WHI) is composed of two randomized, placebo-controlled, double-blind trials in postmenopausal women aged 50 to 79 years at initial screening, testing the effects of estrogen alone (E-alone) and estrogen plus progestin (E P) on coronary heart disease (CHD) as the primary outcome, hip and other fractures and colorectal cancer as secondary outcomes, and pulmonary embolism, breast and endometrial cancers as potential risks. The design and rationale of the PHT trials, including general eligibility and exclusion criteria and considerations regarding sample size and statistical power, have been described previously (1). Postmenopausal hormones have been initiated in menopausal women for the treatment of vasomotor symptoms, mood disturbances, vaginal dryness, and prevention of rapid bone loss for several decades. Despite a paucity of data on effects of initiating hormone use in older women, postmenopausal hormones have also been promoted for the prevention of CHD, osteoporotic fractures, and other diseases that occur years after menopause (2). It is generally recommended (2) that women with a uterus be prescribed a combination of estrogen and progestin to prevent endometrial

Dietary inclusion of whole soy foods results in significant reductions in clinical risk factors for osteoporosis and cardiovascular disease in normal postmenopausal women.

ObjectiveTo determine the effects of dietary inclusion of soy foods on clinical markers for cardiovascular disease (CVD) and osteoporosis in normal postmenopausal women. DesignThis was a single open-group prospective clinical intervention. Forty-two normal postmenopausal women consumed three daily servings for 12 consecutive weeks of whole soy foods containing approximately 60 mg/d of isoflavones. Blood and urine specimens were obtained at baseline and after 12 weeks of dietary intervention. ResultsSerum and urine levels of individual and total isoflavones increased significantly (7–19 fold, p < 0.001) from baseline. A significant increase (9.3%, p < 0.05) in the mean lag-time of low-density lipoprotein cholesterol oxidation was seen and was positively correlated with serum phytoestrogens (p < 0.05). Significant increases were found in mean levels of high-density lipoprotein cholesterol (HDLc) (3.7%, p < 0.05) and serum osteocalcin (10.2%, p < 0.025). Significant decreases were observed in total cholesterol:HDLc ratios (5.5%, p < 0.006) and mean urinary N-telopeptide excretion (13.9%, p < 0.02). Urinary excretion of total isoflavones was negatively correlated with very-low-density lipoprotein cholesterol, triglycerides, and total cholesterol:HDLc ratios (p < 0.04). No significant changes from baseline in HDLc peroxidation, total cholesterol, triglycerides, low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol, bone-specific alkaline phosphatase, follicle-stimulating hormone, or estradiol levels were observed. ConclusionsDietary inclusion of whole soy foods containing 60 mg/d of isoflavones results in significant serum levels of phytoestrogens and reductions in several key clinical risk factors for CVD and osteoporosis in normal postmenopausal women. Long-term, placebo-controlled clinical trials are needed to evaluate the effect of phytoestrogens on the clinical endpoints of CVD and osteoporosis in this population.

A Randomized, Multicenter Trial of Safety and Efficacy of the NovaSure System in the Treatment of Menorrhagia

STUDY OBJECTIVE To compare the safety and effectiveness of the NovaSure impedance-controlled endometrial ablation system with hysteroscopic wire loop resection plus rollerball ablation for treatment of excessive uterine bleeding in premenopausal women. DESIGN Randomized, multicenter, double-arm study (Canadian Task Force classification I). SETTING Nine academic medical centers and private offices. PATIENTS Two hundred sixty-five premenopausal women with symptomatic menorrhagia. INTERVENTION Ablation performed with the NovaSure system or wire loop resection and rollerball. MEASUREMENTS AND MAIN RESULTS Success [pictorial blood loss-assessment chart (PBLAC) score < or =75] was achieved in 88.3% of NovaSure-treated and 81.7% of rollerball-treated patients. One year after treatment 90.9% and 87.8%, respectively, reported normal bleeding or less (PBLAC < or =100) and 41% and 35%, respectively, experienced amenorrhea (PBLAC = 0). Mean procedure time was 4.2 minutes (average 84 sec) in the NovaSure group and 24.2 minutes in the rollerball group. Local and/or intravenous sedation was administered in 73% of NovaSure patients and 18% of rollerball patients. Intraoperative adverse events occurred less frequently with NovaSure (0.6%) than with rollerball (6.7%). Postoperative adverse events occurred in 13% and 25.3% of patients, respectively. CONCLUSION The NovaSure system was safe and effective in treatment of women with menorrhagia. The procedure is both quick and effective, and eliminates the expense and side effects of endometrial pretreatment.

Mechanisms involved in the protective effect of estradiol-17β on lipid peroxidation and DNA damage

Previous studies from our laboratory have shown that estrogens can protect against lipoprotein peroxidation and DNA damage. In this study, the mechanism of estradiol-17β (E2) action was investigated by comparing E2 with selective scavengers of reactive oxygen species (ROS) in terms of inhibition of 1) human low-density lipoprotein (LDL) peroxidation (measured by the diene conjugation method) and 2) DNA damage (measured by the formation of strand breaks in supercoiled OX-174 RFI DNA). In addition, the direct effect of E2 on the generation of individual ROS was also measured. By use of ROS scavengers, it was determined that lipoprotein peroxidation was predominantly due to superoxide (39%), with some contributions from hydrogen peroxide (23%) and peroxy (38%) radicals. E2 was a more effective inhibitor of peroxidation than all the ROS scavengers combined. In DNA damage, scavengers of hydrogen peroxide, hydroxyl, and superoxide radical offered significant protection (49-65%). E2 alone offered a similar degree of protection, and no additional effect was evident when it was combined with ROS scavengers. E2caused a significant reduction (37%) in the production of superoxide radical by bovine heart endothelial cells in culture but had no effect on the formation of either hydrogen peroxide or hydroxyl radicals. These studies show that 1) the protection offered by E2 in terms of lipid peroxidation could be due to its ability to inhibit generation of superoxide radical and prevent further chain propagation, and 2) in DNA damage protection, E2 mainly appears to inhibit chain propagation.

The North American Menopause Society recommendations for clinical care of midlife women

In celebration of the 25th anniversary of The North American Menopause Society (NAMS), the Society has compiled a set of key points and clinical recommendations for the care of midlife women. NAMS has always been a premier source of information about menopause for both healthcare providers and midli

Defining the Relationship Between Ovarian Hormones and Migraine Headache

Objective.—(1) To determine whether the attack characteristics of migraine differ between different intervals of the menstrual cycle; (2) To ascertain whether the “rate of change,”“magnitude of change,” or “total burden” of urinary hormone metabolites correlates with headaches outcome measures during different intervals of the menstrual cycle.

Medical Oophorectomy With and Without Estrogen Add‐Back Therapy in the Prevention of Migraine Headache

Objectives.—To determine the preventive benefit of “medical oophorectomy” and transdermal estradiol in women with migraine.

Ovarian 'tumor' of the adrenogenital syndrome: the first reported case.

We report the case of a 36-year-old woman with congenital adrenal hyperplasia from 21-hydroxylase deficiency who had been receiving replacement therapy with corticosteroids since birth. At the age of 35 years, she developed abrupt aggravation of her virilizing symptoms and underwent an adrenalectomy and partial left oophorectomy. Persistent virilization and high testosterone levels led to right oophorectomy and completion left oophorectomy 6 months later. Each adnexa contained ovarian or paraovarian soft brown masses that on microscopic examination were identical to the testicular tumor of the adrenogenital syndrome. This represents the first reported case of this pathology (well known in the testis) in the ovary.

Birth of a Western Lowland Gorilla (Gorilla gorilla gorilla) Following In Vitro Fertilization and Embryo Transfer

A 21‐year‐old multiparous female exhibiting 31–41 day menstrual cycles was given hFSH (225 IU/day, Metrodin 75, from cycle day 3 through 9 (menses = day 1) and hCG (10,000 IU, Profasi, on day 10 to stimulate follicular development. At 35 h after hCG, under isoflurane (AErrane) anesthesia, follicles were aspirated by controlled suction under transvaginal ultrasound guidance. Metaphase II oocyctes (n = 11) were placed in modified human tubal fluid (mHTF, 100 μl) medium under oil at 37°C in humidified 5% CO2. Frozen semen, collected by voluntary ejaculation, was thawed (70°C H2O bath, 6 sec), diluted slowly, centrifuged, and resuspended in mHTF, and 160,000 motile spermatozoa/ml were added at 6 h after oocyte recovery. At 21 h postinsemination (p.i.) eight oocytes were at the two‐cell stage, five were cryopreserved, and three were cultured to the six‐ to eight‐cell stage in mHTF with granulosa cells before transcervical uterine transfer at 47 h p.i. using a Teflon catheter. Micronized progesterone (400 mg/d) was orally administered for 10 weeks posttransfer (p.t.). Ultrasound examination revealed a single fetus at 15 weeks p.t., and unassisted delivery of a live 1.37 kg female infant occurred at 29 weeks. Am. J. Primatol. 41:247–260, 1997.

Hypothalamic amenorrhea: clinical perspectives, pathophysiology, and management.

The development of functional hypothalamic amenorrhea reflects an individuals response to environmental stressors and life-style variables. In this disorder there are no detectable anatomic abnormalities with respect to the hypothalamic-pituitary-ovarian-endometrial axis. Current evidence suggests that the common underlying defect is a decrease in the activity of the hypothalamic gonadotropin-releasing hormone pulse generator. Of the neuroendocrine factors that appear to regulate gonadotropin-releasing hormone activity, the opiate and dopamine neuronal systems have been implicated as factors that are responsible in part for the decreased secretion of gonadotropin-releasing hormone. Because of the functional nature of this disorder, reactivation of the hypothalamic-pituitary unit would be expected to take place in most women after accommodation to environmental stressors or modification in life-style. For women with persistent anovulation, treatment with estrogen-replacement therapy should be offered. In those desiring fertility, ovulation induction with pulsatile gonadotropin-releasing hormone would be the most effective modality.