Temporal trends in human semen parameters in New England in the United States, 1989-2000.

The current study explores trends in semen parameters in New England in the United States. A retrospective review was performed of 551 semen analysis records from 1989 to 2000 at Vincent Memorial Andrology Laboratory of Massachusetts General Hospital. After age adjustment, semen pH and motility significantly increased 0.05 units/year and 2.33%/year, respectively, while sperm with normal morphology decreased 0.33%/year. Sperm concentration showed a small upward trend. The year of birth in the present study ranged from 1932 to 1981; 2% were born between 1932 and 1941, 13% between 1942 and 1951, 48% between 1952 and 1961, 36% between 1962 and 1971, and 1% were born between 1972 and 1981. There were significant positive relationships between year of birth and semen volume (0.04 mL/1-year interval increase in year of birth) and motility (0.61 percent/1-year interval increase in year of birth), as well as with sperm concentration and morphology. Overall, there were temporal and year of birth trends in several human semen parameters.

Neuropsychological effects of methyltestosterone in women using menopausal hormone replacement.

To observe the effects of androgen replacement on neuropsychological measures in menopausal women, healthy menopausal women already using replacement estrogen were studied in a randomized, double-blind, active placebo-controlled, crossover comparison between two 8-week periods of treatment with (1) 0.625 mg oral esterified estrogen (E) alone and (2) in combination with 1.25 mg oral methyltestosterone (meT). After an initial baseline session, data were gathered at the end of two treatment periods. Scores on standardized psychological tests and computerized reaction times were compared between treatments, as was an overall outcome score that combined all measures. Added meT significantly improved scores on a test of complex information processing, the Switching Attention Test, but not on other tests. Mean outcome score showed no net change and wide variation. Fourteen subjects had outcome scores >1 SD from the mean, and 21 had no change. In the estrogen alone condition, three measures predicted favorable outcome with added meT: surgically compromised ovarian function, fewer physical symptoms, and higher score on a self-image measure of creativity. Added meT treatment may improve complex information processing. Despite wide disparities in outcome, an increased chance of overall improvement may be predicted by specific pretreatment measures.

Preliminary observations on differing psychological effects of conjugated and esterified estrogen treatments.

During a double-blind comparison of menopausal replacement therapy with estrogen alone compared with estrogen plus methyltestosterone (meT), subjects who had been on conjugated equine estrogen (CEE) said they felt better when placed on esterified estrogen (EE). We, therefore, tested whether these estrogen treatments differed in their neuropsychological effects. Subjects were 34 healthy menopausal respondents to advertisements younger than age 66 who were on CEE at baseline. Each was randomized into the EE condition, either immediately after baseline or after they first took EE plus added meT for 8 weeks. We compared neuropsychological measures between these two conditions. Data included cognitive performance test results and symptom self-ratings. Multivariate techniques were used to adjust for the effects of treatment order. Compared with prior CEE treatment, EE treatment was associated with significantly improved scores on the Zung Self-Rated Depression Scale and on Switching Attention Test performance. Further investigation is warranted to determine if different forms of estrogen replacement induce different neuropsychological effects.

Has the impact of hormone replacement therapy on health-related quality of life been undervalued?

Previous economic evaluations of hormone replacement therapy (HRT) have restricted positive effects to alleviation of postmenopausal symptoms and negative effects to drug side effects. We studied the association between HRT use and postmenopausal women's valuation of both health-related quality of life and potential treatment side effects. Postmenopausal women with either a documented first vertebral fracture within the past 5 years or no history of osteoporotic fractures were recruited from Olmsted County, Minnesota, and from Dartmouth-Hitchcock Medical Center in New Hampshire to participate in a study to assess quality of life and women's attitudes toward osteoporosis prevention. Women's valuations of their current health and potential HRT-related side effects were quantified as quality-adjusted life years (QALYs) assessed by an automated utility assessment instrument (U-Titer) and the time tradeoff technique, by a vertical rating scale, and by estimated quality of well-being (QWB) scores. Health status was measured using the Medical Outcomes Study SF-36. Regression methods were used to assess the impact of current HRT use on health-related quality of life and valuation of side effects. There were 106 women with vertebral fracture and 180 with no history of hip, wrist, or vertebral fractures. Altogether, 116 (40.6%) women were currently taking HRT, 64 (22.2%) had taken HRT in the past, and 106 (37.1%) women had never taken HRT. Current HRT users had higher time tradeoff QALYs than never and past HRT users, with gains ranging from 15.0 to 83.7 days per year for current users relative to the others. Benefits were largest for women with a vertebral fracture and limitations in activities. The secondary QALY measures also showed significantly higher values for current HRT users compared with other women, as did SF-36 subscales for general health, physical function, role-emotional function, and vitality. There was substantial variability in women's perceptions of HRT side effects. Overall, the proportion of women willing to trade time to avoid bleeding was largest, at 95.5%, followed by breast tenderness, weight gain, and endometrial biopsy at 90.4%, 87.4%, and 82.7%, respectively. Current HRT users had higher health-related quality of life than past or never users according to all measures studied. Women's perceptions of potential side effects were highly variable and should be considered by physicians when prescribing an HRT regimen. If, as our results suggest, postmenopausal therapy has positive effects beyond the immediate postmenopausal years, previous economic studies may have underestimated the value of HRT.

The aging ovary.

During reproductive life, ovarian steroid biosynthesis is gonadotropin dependent and occurs in theca and granulosa cells. In the menopausal ovary, there is atresia of ovarian follicles, with sparing of the androgen-producing theca-interstitial cell component. The aging ovary, therefore, produces significantly reduced amounts of estrogen, with continued, though decreased, androgen production. After menopause, ovarian estradiol biosynthesis is minimal, with circulating estrogen being derived principally from peripheral aromatization of ovarian and adrenal androgens. Androgen biosynthesis from the adrenal gland, in addition to that from the ovary, decreases with age. Although ovarian androgen production declines with age, there is not an abrupt decrease as is seen with ovarian estrogen levels at the time of menopause. The biological activity of these steroids, either before or after menopause, depends on the amount of steroid available in the unbound fraction. To this end, sex hormone-binding globulin (SHBG) levels are an important determinant of hormone action. Not only does the concentration of SHBG influence the biological effect of testosterone and estradiol, but these steroids also regulate SHBG concentrations.

Oral contraceptives and smoking, current considerations: recommendations of a consensus panel.

In a closed meeting, members of the consensus panel evaluated the presentations of the scientific panel and developed a series of recommendations. They outlined clinical imperatives related to the identification and education of patients who smoke, the physician's role in smoking cessation, and the prescription of oral contraceptives for patients who smoke. They also outlined research objectives for the future. The most important suggestions include the following: All patients should be asked about their smoking status at every visit, and all smokers should be encouraged and helped to quit. The decision to prescribe an oral contraceptive requires a detailed personal and family history of thrombotic disease. Measurement of lipid profile should be considered, along with exercise and dietary intervention, for smokers >35 years old who use or request oral contraceptives. Patients >35 years old who smoke heavily (>15 cigarettes/d) should be denied the use of oral contraceptives. Preliminary data suggest that an oral contraceptive with the very low dose of 20 micrograms ethinyl estradiol may be safer for oral contraceptive users who smoke, even for those >35 years old who have an occasional cigarette, but these laboratory findings require clinical corroboration.

PIP: This article summarizes the activities of a conference in Montreal, Canada, entitled "Oral Contraceptives and Smoking: Current Considerations." Members of the consensus panel evaluated the presentations of the scientific panel and developed a series of recommendations. The clinical imperatives related to the identification and education of patients who smoke, physicians¿ role in smoking cessation, and prescription of OCs for patients who smoke were elaborated. The following recommendations were made: 1) encourage patients who smoke to quit smoking; 2) counsel patients regarding OC benefits; furthermore, counsel patients concerning the risks of concomitant smoking and OC use; and 3) prescribe 20 mcg ethinyl estradiol for women who smoke. In view of the remaining unanswered questions, the panel outlined several research objectives for the future.

Preparation by differential gradient centrifugation is better than swim-up in selecting sperm with normal morphology (strict criteria).

OBJECTIVE: To evaluate two commonly used methods of sperm preparation with respect to their effects on sperm morphology (strict criteria). DESIGN: Auto-controlled, split sample study performed on the semen of 74 male partners of couples enrolled for IVF. SETTING: In vitro fertilization and andrology laboratories at a tertiary care, major teaching hospital. PATIENT(S): Seventy-four male partners of couples who were scheduled to undergo IVF. INTERVENTION(S): Equal halves of the same semen sample were evaluated for strict criteria sperm morphology before and after preparation by differential gradient centrifugation using Percoll (Pacific Andrology, Montrose, CA) and by the standard swim-up method. MAIN OUTCOME MEASURE(S): The percentage of morphologically normal sperm was assessed using strict criteria before and after the two methods of sperm preparation. Specific parameters studied were individual abnormalities of the head, midpiece, and tail. RESULT(S): Sperm preparation using differential gradient centrifugation with Percoll produced a significantly greater number of specimens with normal sperm morphology and also showed higher absolute quantitative improvement over the swim-up method. The two methods were comparable in regard to their effects on specific sperm abnormalities (i.e., head, midpiece, and tail defects). CONCLUSION(S): The differential gradient sperm separation method using Percoll is superior to the swim-up method for selecting sperm with normal morphology as assessed by strict criteria. Because sperm morphology as assessed by strict criteria is a good predictor of oocyte fertilization, this method can be recommended as the method of choice for assisted reproductive technology laboratories. Use of this method may help improve outcome by increasing fertilization rates.

The effect of a carbohydrate-rich beverage on mood, appetite, and cognitive function in women with premenstrual syndrome.

OBJECTIVE: To test the efficacy of a specially-formulated, carbohydrate-rich beverage (one known to increase the serum ratio of tryptophan to other large neutral amino acids) on the mood, cognitive, and appetitive disturbances of premenstrual syndrome (PMS). METHODS: Twenty-four women with confirmed PMS were enrolled in a double-blind, crossover study to test the efficacy of the specially-formulated beverage compared with two other isocaloric products on PMS symptoms. The study was conducted over three menstrual cycles preceded by a 1-month placebo run-in. Patients were tested at home or work using an interactive computer-telephone system. Standardized measurements of mood, cognitive performance, and food cravings were made before and 30, 90, and 180 minutes after consumption of active and placebo beverages during the late luteal phase of the menstrual cycle. RESULTS: The experimental carbohydrate intervention significantly decreased self-reported depression, anger, confusion, and carbohydrate craving 90-180 minutes after intake. Memory word recognition was also improved significantly compared with scores obtained during the placebo run-in month (P < .05). The isocaloric placebo interventions had no significant effect on any of these measures. CONCLUSION: The results suggest that the psychological and appetitive symptoms of PMS can be relieved after consuming a specially-formulated, carbohydrate-rich beverage known to increase serum tryptophan levels.

Interlaboratory interprotocol comparison of indirect immunobead assay for sperm-associated antibodies in serum.

This investigation was designed to study the effect of two different protocols on the indirect sperm-associated antibody test on serum performed using Bio-Rad immunobead (IBT) at two andrology laboratories. Aliquots of 31 serum samples from infertile couples were analyzed by both protocols. The IBT was negative by both protocols (100% concordance) for 18 serum samples. Seven of the 13 remaining samples were positive by both protocols (> or = 10% bead attachment by protocol A and > or = 20% bead attachment by protocol B), for a concordance of 54%. The remaining six samples were positive by one of the two protocols. The overall concordance for positive and negative results was 81% (25 of 31 samples). Protocol A detected a higher percentage of bead attachments for IgG and IgA, while protocol B detected a higher percentage of bead attachments for IgM. The discordance in the results of IgA attachment obtained by the two protocols was statistically significant (p < .05). A standardized, uniform protocol for the indirect IBT is needed.

Parathyroid hormone for the prevention of bone loss induced by estrogen deficiency.

BACKGROUND: Analogues of gonadotropin-releasing hormone (GnRH) are often given to induce hypogonadism in women who have estrogen-dependent disorders such as endometriosis and uterine leiomyomas. Because estrogen deficiency causes bone loss, concern about premature osteoporosis has prevented long-term therapy with GnRH analogues. We conducted a study to determine whether parathyroid hormone could prevent bone loss in women receiving therapy with GnRH analogues. METHODS: We administered human parathyroid hormone (40 micrograms subcutaneously daily) to 20 of 40 women with endometriosis who were being treated with nafarelin (200 micrograms intranasally twice daily) for six months; the remaining 20 women received only nafarelin. Cortical and trabecular bone density and biochemical markers of bone turnover were measured every three months during the six-month study period. RESULTS: Serum estradiol concentrations fell to postmenopausal values in 36 of the 40 women. In the women who received nafarelin alone, the mean (+/- SE) bone density in the lumbar spine decreased by 2.8 +/- 0.5 percent (P < 0.001) when measured in the anteroposterior projection and by 3.5 +/- 0.8 percent (P < 0.001) when measured in the lateral projection. In contrast, bone density in the lumbar spine did not change when measured in the anteroposterior projection and increased by 3.4 +/- 1.2 percent when measured in the lateral projection (P = 0.01) in the women who also received parathyroid hormone. Bone density at the femoral neck decreased slightly and similarly in both groups. Radial bone density did not change in either group. Serum alkaline phosphatase and osteocalcin concentrations and urinary hydroxyproline and pyridinoline excretion increased (P < 0.001) in the women who received nafarelin plus parathyroid hormone. CONCLUSIONS: Parathyroid hormone can prevent bone loss in the lumbar spine in young women with estrogen deficiency caused by treatment with GnRH analogues.

Comparative study of different laser systems.

OBJECTIVE: To review lasers, laser physics, laser-tissue interaction, delivery systems, and their clinical applications relevant to gynecology. SETTINGS: Gynecological Service at Massachusetts General Hospital (MGH) and MGH Laser Center. INTERVENTIONS: None. DESIGN: Laser literature review and personal experiences of the authors were used to prepare this manuscript. CONCLUSIONS: Lasers have been used in gynecologic practice for cutting and coagulating purposes. Photodynamic therapy has been used clinically for malignant conditions and is being investigated for dysplastic lesions of the lower genital tract and for endometrial ablation. Laser welding has potential, but further work is required in this field before it finds a clinical application. The main lasers used in gynecology are CO2, neodymium-yttrium aluminum garnet (Nd:YAG), and potassium tatanyl-phosphate-doubled Nd:YAG. Pulsed Ho:YAG laser looks promising, as does diode lasers. Holmium-yttrium aluminum garnet and diode lasers will be soon available commercially. Improvements in delivery systems have increased user friendliness, and more developments in this area are anticipated, for example, a fiber-optic delivery system for CO2 lasers. We believe that enhanced understanding of laser technology will provide unique applications for development in gynecology.

Differential effects of estrogen on low-density lipoprotein subclasses in healthy postmenopausal women.

The use of estrogen by postmenopausal women decreases plasma low-density lipoprotein (LDL) cholesterol levels. To determine whether LDL subclass profiles influence this response, we studied 31 healthy postmenopausal women who were administered two doses (0.625 and 1.25 mg/d) of conjugated equine estrogen in a placebo-controlled double-blind crossover study. Lipid-stained gradient gels were used to categorize LDL subclass patterns. All women were classified as LDL subclass pattern A (predominant LDL peak > or = 260 A). Within the pattern A classification, there were 12 women during placebo treatment with LDL subclass I pattern (predominant LDL peak > 271 A) and 19 women with LDL subclass II pattern (predominant LDL peak < or = 271 and > or = 260 A). Postmenopausal women with LDL subclass I on placebo treatment had significantly lower LDL cholesterol levels compared with women having LDL subclass II (126 +/- 28 v 147 +/- 23 mg/dL, P < .03). Postmenopausal women with LDL subclass I also had significantly (P < .05) lower very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, and VLDL apo B levels and significantly higher (P < .05) high-density lipoprotein 2 (HDL2) cholesterol, HDL3 cholesterol, and HDL2 apo A-I levels. Estrogen replacement significantly (P < .05) decreased LDL cholesterol levels and increased VLDL and LDL triglyceride, HDL2 and HDL3 cholesterol and apo A-I, and HDL2 apo A-II levels to a similar extent in postmenopausal women with LDL I or II subclass patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormal uterine bleeding in the perimenopause.

Abnormal uterine bleeding is probably one of the most common gynecologic complaints in the perimenopause. It is a significant cause of hysterectomy, which is the second most common surgical procedure performed on women in the United States, and thus is a major health issue. Management consists of a stepwise evaluation of all possible organic causes of uterine bleeding. Advancements in technology have allowed considerable improvements in the resolution of many diagnostic tools. Direct visualization of the uterine cavity is now an invaluable adjunct to blind endometrial sampling. Consequently, therapy can be tailored more appropriately and efficiently, either by newly developed medical strategies or through selective, minimally invasive surgery. In light of these perspectives, some of the recent diagnostic and therapeutic trends in the management of abnormal uterine bleeding in perimenopausal women are presented.

Caffeine and other predictors of bone density among pre- and perimenopausal women.

We evaluated the influence of dietary, anthropomorphic, and hormonal factors on bone density in a cross-sectional sample of 281 pre- and perimenopausal women age 50-60 years living in Massachusetts. The sample included only women who had intact ovaries and were not currently using estrogen. Information on diet was obtained through a semiquantitative food frequency questionnaire. We measured bone density using single-photon absorptiometry in the non-dominant arm in two sites: the midshaft and the ultradistal radius. We observed no important associations between midshaft bone density and dietary variables but found linear relations between ultradistal radius bone density and body mass index [b = 1.10 gm/cm2 per kg/m2, standard error (SE) = 0.56], follicle-stimulating hormone (FSH) (b = -0.36 gm/cm2 per IU/liter, SE = 0.15), and several nutrients: calcium (b = 0.012 gm/cm2 per mg/day, SE = 0.007), retinol (b = 0.002 gm/cm2 per IU/day, SE = 0.0008), vitamin C (b = 0.025 gm/cm2 per mg/day, SE = 0.013), and vitamin D (b = 0.040 gm/cm2 per IU/day, SE = 0.018). We could not clearly distinguish the independent contribution of these micronutrients, however, because many were commonly ingested together in the form of supplements. Caffeine was inversely associated with bone density (b = -0.035, SE = 0.017) independent of dietary, anthropometric, and hormonal factors. Analyses of individual caffeinated beverages revealed consistent inverse associations for coffee (b = -3.42 gm/cm2 per cups/day, SE = 1.49), tea (b = -2.85 gm/cm2 per cups/day, SE = 1.56), and caffeinated cola (b = -14.0 gm/cm2 per cans/day, SE = 5.1), but not for decaffeinated coffee or decaffeinated cola [corrected]. [ABSTRACT TRUNCATED AT 250 WORDS)

Injury and adhesion formation following ovarian wedge resection with different thermal surgical modalities.

The purpose of this study is to determine the role of bleeding, acute thermal damage, and charring in adhesion formation. Postoperative adhesions were compared following ovarian wedge resection in 48 rabbits using different lasers, electrosurgery, and scalpel. Twelve ovaries were sectioned per modality, in randomized pairs. Acute thermal injury as assessed by histology, bleeding, and charring differed among the modalities used. Adhesions were assessed 4 weeks later, by an investigator completely blinded of the treatment protocol. The adhesion scores were 11.6 +/- 8.0 with pulsed Er:YAG laser; 11.9 +/- 7.5 with scalpel; 8.3 +/- 9.3 with electrocautery; 6.7 +/- 8.8 with a continuous (c.w.) Nd:YAG laser; 5.3 +/- 4.8 with c.w. CO2 laser; 3.1 +/- 2.7 with pulsed CO2 laser; 1.7 +/- 1.8 with pulsed Ho:YAG laser; and 0.8 +/- 1.5 in the control (no resection) group. Ho:YAG, Nd:YAG, and electrocautery were completely hemostatic. Bleeding was minimal with the CO2 lasers. Er:YAG and scalpel caused maximum bleeding, requiring hemostatic measures to prevent exsanguination. Charring occurred with electrocautery, CO2 laser, and Nd:YAG laser. Bleeding and charring correlated with adhesion formation, but the histological depth of thermal damage did not. The Ho:YAG laser is a hemostatic, fiber-optic compatible laser causing significantly fewer adhesions (P < 0.04) than scalpel, electrocautery, Nd:YAG, Er:YAG, and c.w. CO2 lasers. Clinical use of the Ho:YAG laser, and the role of carbonization in promoting adhesions, deserve further study.

Endometrial ablation by means of photodynamic therapy with photofrin II.

OBJECTIVE: Photodynamic therapy is a technique in which tissue is irradiated with light after the use of a photosensitizing drug that produces singlet oxygen, which has a cytotoxic effect. The feasibility of using photodynamic therapy with photofrin II for endometrial ablation was studied. STUDY DESIGN: Fifty-eight rabbits were studied. Preferential uptake of photofrin II by endometrial tissue, compared with the myometrium, was established by drug extraction and fluorescence microscopy after administration of photofrin II intravenously. Dosimetry for endometrial ablation was established by administering photofrin II in 1, 2, 5, and 10 mg/kg doses and laser light (630 nm) at radiant exposures of 100 and 200 J/cm2. Histologic examination was performed at 24 hours, 5 days, and 10 days after treatment. There were two control groups. One group received laser light but no photofrin II, and the other received photofrin II without laser light. RESULTS: The concentration of photofrin II was three times higher in the endometrium than in the myometrium at doses of 1 and 2 mg/kg. Fluorescence microscopy of frozen sections of endometrium and myometrium showed a predominantly perivascular fluorescence from photofrin II. A dose of 1 and 2 mg/kg and a flow of 100 J/cm2 was adequate for endometrial ablation in rabbits. At 24 hours after treatment there was extensive hemorrhage and evidence of cell death in the entire endometrium and mild hemorrhage in 10% to 50% of the inner circular layer of the myometrium. At 5 days after treatment necrosis of the entire endometrium and the inner half of the myometrium was seen, but the outer half of the myometrium and the serosa were normal. There were no cases of uterine perforation. Similar results were seen at 10 days after treatment, except for the additional presence of inflammatory cells. Neither control group (drug without light, light without drug) showed any injury to the endometrium at 24 hours. CONCLUSION: We conclude that endometrial ablation can be effectively achieved in rabbits by means of photodynamic therapy with photofrin II without significant complications.