This analysis was designed to determine the efficacy of anastrozole, an aromatase inhibitor, combined with testosterone in a subcutaneous implant in preventing elevated estradiol levels and the subsequent side effects of excess estrogen associated with testosterone therapy. It also allowed for the establishment of normative ranges of serum testosterone levels on subcutaneous implant therapy. The study participants were 344 men who were accrued to an institutional review board-approved cohort study between April 2014 and 2017. Efficacy of the subcutaneous combination implant in maintaining low estradiol levels was evaluated. Serum levels of testosterone and estradiol were measured throughout the implant cycle, at week 4, and when symptoms returned. Correlations between patient demographics, dosing, and serum levels on therapy were evaluated. Mean testosterone dose was 1827 ± 262 mg. Mean anastrozole dose was 15.3 ± 3.2 mg with the majority of men receiving 16 mg of subcutaneous anastrozole. The mean interval of insertion was 4.8 months. Low estradiol levels were maintained throughout the implant cycle. Mean T level at week 4 was 1183 ± 315 ng/dl and 553 ± 239 ng/dl when symptoms returned. Levels of testosterone on therapy inversely correlated with body mass index. There were no adverse events attributed to testosterone or anastrozole therapy. Subcutaneous anastrozole delivered simultaneously with testosterone allowed for higher dosing of testosterone and less frequent intervals of insertion. Low-dose anastrozole released from the combination implant maintained low estradiol levels throughout the implant cycle and prevented clinical side effects attributed to excess estrogen.

Background Testosterone implants have been used for over eighty years to treat symptoms of hormone deficiency in pre and postmenopausal women. Evidence supports that androgens are breast protective. However, there is a lack of data on the long-term effect of testosterone therapy on the incidence of invasive breast cancer (IBC). This study was specifically designed to investigate the incidence of IBC in pre and postmenopausal women (presenting with symptoms of androgen deficiency) treated with subcutaneous testosterone implants or testosterone implants combined with anastrozole. Methods The 10-year prospective cohort study was approved in March 2008 at which time recruitment was initiated. Recruitment was closed March 2013. Pre and postmenopausal women receiving at least two pellet insertions were eligible for analysis ( N = 1267). Breast cancer incidence rates were reported as an unadjusted, un-weighted value of newly diagnosed cases divided by the sum of ‘person-time of observation’ for the at-risk population. Incidence rates on testosterone therapy were compared to age-specific Surveillance Epidemiology and End Results (SEER) incidence rates and historical controls. Bootstrap sampling distributions were constructed to verify comparisons and tests of significance that existed between our results and SEER data. Results As of March 2018, a total of 11 (versus 18 expected) cases of IBC were diagnosed in patients within 240-days following their last testosterone insertion equating to an incidence rate of 165/100000 p-y, which is significantly less than the age-matched SEER expected incidence rate of 271/100000 p-y ( p < 0.001) and historical controls. Conclusion Long term therapy with subcutaneous testosterone, or testosterone combined with anastrozole, did not increase the incidence of IBC. Testosterone should be further investigated for hormone therapy and breast cancer prevention.

Publisher Summary This chapter covers the abundance estimation, the range of techniques by which the size of a population of marine mammals can be estimated. When it is difficult to estimate absolute abundance with an acceptably low bias, relative abundance indices are often used instead. These are indices that are believed to be proportional to population size, apart from stochastic variation, allowing trends in the population in space and/or time to be assessed. The main techniques for abundance estimation (relative or absolute) are distance sampling, mark–recapture, migration counts, and colony counts. Many populations of large whales conveniently file past coastal watch points on migration, allowing observers to count a large proportion of the population. This count can then be corrected for animals passing outside watch periods to estimate population size. The methods usually used for modeling migration counts were developed for the analysis of surveys of the California gray whale (Eschrichtius robustus). In colony count abundance estimation researchers often make counts of populations when they gather for breeding and pupping at certain times of the year. Often photographs are taken of the colonies. These are brought back to the laboratory for analysis and form a permanent record of the population.

Objective: Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. Methods: A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to “testosterone-letrozole” and subsequently, “testosterone-letrozole with chemotherapy” was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. Results: There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Conclusions: Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

109 Background: Menopausal symptoms can be severe in breast cancer survivors in whom estrogen therapy is contraindicated. Our previous pilot trial demonstrated that testosterone (T) combined with anastrozole (A) in subcutaneous implants provided therapeutic T levels without elevating estradiol. Our current goal was to document the clinical effect of T+A combination implants (no estrogen) on menopausal symptoms. Methods: This IRB approved study was designed to prospectively follow breast cancer survivors (stage 0-4) treated with subcutaneous T+A, for breast cancer recurrence. The therapeutic effectiveness of T on the relief of psychological, somatic and urogenital symptoms was documented using the validated, self administered, 11 item Menopause Rating Scale. Patients completed the survey prior to and following therapy. Results: Over 950 T/T+A pellet insertions have been performed in breast cancer survivors since 2006. Since 4/2013, 72 patients have been enrolled in the study. T dosing is weight based. Implants are inserted at 3-month intervals on average. Therapeutic T levels were confirmed without elevation of estradiol in any postmenopausal survivor. There have been no cancer recurrences in up to 8 years of therapy. A single patient with active metastatic disease at enrollment developed ascites. There was statistically significant improvement (P < 0.0001) in psychological symptoms (depression, irritability/aggression, anxiety), somatic symptoms (hot flashes/sweating, heart discomfort, sleep problems/insomnia, physical exhaustion, impaired memory, joint/muscular pain) and urogenital symptoms (vaginal dryness, bladder problems/incontinence, sexual problems). Conclusions: Testosterone in combination with an aromatase inhibitor, delivered by subcutaneous implant, was extremely effective for the relief of hormone deficiency symptoms in breast cancer survivors. Furthermore, this supports testosterone’s therapeutic effect via the androgen receptor. [Table: see text]

Objectives: This study was designed to measure the beneficial effects of continuous testosterone therapy, delivered by subcutaneous implant, in the relief of somatic, psychological and urogenital symptoms in both pre- and post-menopausal patients, utilizing the validated Health Related Quality of Life (HRQOL), Menopause Rating Scale (MRS).Study design: 300 pre- and post-menopausal women with symptoms of relative androgen deficiency, were asked to self-administer the 11-item MRS, at baseline and 3 months after their first insertion of the subcutaneous testosterone implant. Baseline hormone measurements, menopausal status and BMI, were assessed to determine correlation with symptoms and clinical outcome. Main outcome measurements: Changes related to therapy were determined. Total MRS scores as well as psychological, somatic and urogenital subscale scores were compared prior to therapy and following testosterone implant therapy.Results: Pre-menopausal and post-menopausal females reported similar hormone deficiency symptoms. Both groups demonstrated similar improvement in total score, as well as psychological, somatic and urogenital subscale scores with testosterone therapy. Better effect was noted in women with more severe complaints. Higher doses of testosterone correlated with greater improvement in symptoms.Conclusion: Continuous testosterone alone, delivered by subcutaneous implant, was effective for the relief of hormone deficiency symptoms in both pre- and post-menopausal patients. The validated, HRQOL questionnaire, Menopause Rating Scale (MRS), proved a valuable tool in the measurement of the beneficial effects of testosterone therapy in both cohorts. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Walleye pollock (Theragra chalcogramma) otoliths (n = 2,706) recovered from stomachs, small intestines, and colons of 43 northern fur seals (Callorhinus ursinus) were evaluated for size and wear by location in the digestive tract. Pollock fork length was regressed on otolith length after correction for erosion, and age was estimated from the calculated body size. Age-1+ pollock otoliths (≥6.3-mm length) were concentrated in stomachs while age-0 otoliths (≤6.2-mm length) were concentrated in colons. Less than 10% of otoliths were found in the small intestines. Pollock age decreased with progression along seal gastrointestinal tracts. Otolith quality increased along gastrointestinal tracts in numbers ≥20, which was typical of age-0 otoliths recovered from colons. Otolith distribution by age and quality along gastrointestinal tracts suggests that small (≤12 cm) schooling prey are consumed in large volume and passed as a bolus rapidly through the digestive tract before significant erosion of bony remains occurs; while larger prey are eaten in smaller volume and subjected to otolith erosion due to longer retention in the stomach. Our results illustrate the importance of multiple sampling strategies to comprehensively represent prey size in pinniped diet.

Pinniped blubber supports multiple functions including thermoregulation, reproduction, and buoyancy. Although blubber depth is frequently used as an indicator of health, the effect of sample site and seasonality are rarely taken into account. We monitored blubber depth via imaging ultrasound at 10 sites monthly for 1 year in 2 adult Steller's sea lions (Eumetopias jubatus) and 3 adult harbor seals (Phoca vitulina). Blubber of harbor seals was thicker and more variable than blubber of sea lions, and was thickest in winter. Changes in harbor seal blubber at all sites tracked variation due to season and mass. Sea lion blubber changed with mass only at specific sites, with no seasonal effect. The differing effects of season, mass, and location on the body must be carefully considered in both species before any interpretation of condition.

Skates (family Rajidae) are oviparous and lay tough, thick-walled eggs. At least some skate species lay their eggs in spatially restricted nursery grounds where embryos develop and hatch (Hitz, 1964; Hoff, 2007). After hatching, neonates may quickly leave the nursery grounds (Hoff, 2007). Egg densities in these small areas may be quite high. As an example, in the eastern Bering Sea, a site <2 km2 harbored eggs of Alaska skate (Bathyraja parmifera) exceeding 500,000/km2. All skate nursery grounds have been identified over soft sea floors (Lucifora and Garcia, 2004; Hoff, 2007).

We measured delta N-15 and delta C-13 values and tooth width from the first 4 years' dentinal growth layer groups (GLGs) in the teeth of 113 female Steller sea lions (Eumetopias jubatus (Schreber, 1776)) born between 1960 and 1983, a period that included a large population decrease and a climate regime shift. A linear discriminant analysis on the 613 C and delta N-15 values estimated 60% of Steller sea lions were weaned in their 1st year, 30% in their 2nd year, and 8% in their 3rd year. GLG-1 was wider in "weaned" animals than those still "nursing" in their 2nd year, suggesting that faster growing pups weaned earlier. Except during the regime shift, the average age at weaning increased and the size of GLG-1 in weaned animals decreased. We suggest that during the regime shift a greater proportion of pups which survived (to have their teeth sampled for this study) grew faster and were weaned by the end of their 1st year. We hypothesize that the long-term weaning age increase and growth rate decrease are consistent with a change in relative mortality of weaned pups and those that continued to nurse, possibly caused by a reduction in available resources, characterized as a switch from a "live-fast" to a "live-slow" life history.

Between 1995 and 2002, we surveyed fish assemblages at seven oil platforms off southern and central California using the manned research submersible Delta. At each platform, there is a large horizontal beam situated at or near the sea floor. In some instances, shells and sediment have buried this beam and in other instances it is partially or completely exposed. We found that fish species responded in various ways to the amount of exposure of the beam. A few species, such as blackeye goby (Rhinogobiops nicholsii), greenstriped rockfish (Sebastes elongatus), and pink seaperch (Zalembius rosaceus) tended to avoid the beam. However, many species that typically associate with natural rocky outcrops, such as bocaccio (S. paucispinis), cowcod (S. levis), copper (S. caurinus), greenblotched (S. rosenblatti), pinkrose (S. simulator) and vermilion (S. miniatus) rock-fishes, were found most often where the beam was exposed. In particular, a group of species (e.g., bocaccio, cowcod, blue (Sebastes mystinus), and vermilion rockfishes) called here the "sheltering habitat" guild, lived primarily where the beam was exposed and formed a crevice. This work demonstrates that the presence of sheltering sites is important in determining the species composition of man-made reefs and, likely, natural reefs. This research also indicates that adding structures that form sheltering sites in and around decommissioned platforms will likely lead to higher densities of many species typical of hard and complex structure.

Steller sea lion ( Eumetopias jubatus (Schreber, 1776)) populations have had differing dynamics in different regions of Alaska over the past 30 years. The western population (west of 144°W, near Cape Suckling) declined by approximately 85% between the 1970s and 2000, while the eastern population has increased at a rate of over 3%/year. Past research has indicated that the decline in the western population likely resulted from decreased juvenile survival and smaller declines in adult female survival and reproduction. Based on repeated observations (1987–2003) of sea lions branded as pups at Marmot Island (58.216°N, 151.840°W; western population; branded in 1987–1988) and at the Forrester Island rookery complex (54.859°N, 133.539°W; eastern population; branded in 1994–1995), we used mark–resight analyses to estimate age-specific survival probabilities. Juvenile sea lion survival probability at Marmot Island from 1988 to 1991 was lower than survival estimates at that location in the 1970s (assumed stable population) and lower than juvenile survival at Forrester Island from 1995 to 1998 (increasing population). Adult female survival at Marmot Island from 1992 to 2003 was only slightly reduced compared with that in the 1970s but was substantially lower than that at Forrester Island (1999–2003). In addition, and contrary to the typical pattern (e.g., Forrester Island), adult female survival probabilities at Marmot Island were indistinguishable from adult male survival probabilities. This suggests that regardless of which factors altered the dynamics of the western Steller sea lion population, they differentially affected females.

Marine Mammal ScienceVolume 22, Issue 2 p. 486-491 DECLINE IN NORTHERN FUR SEAL (CALLORHINUS URSINUS) PUP PRODUCTION ON THE PRIBILOF ISLANDS Rod G. Towell, Rod G. Towell National Marine Mammal Laboratory, Alaska Fisheries Science Center, 7600 Sand Point Way NE, Seattle, Washington 98115, U.S.A. E-mail: [email protected]Search for more papers by this authorRolf R. Ream, Rolf R. Ream National Marine Mammal Laboratory, Alaska Fisheries Science Center, 7600 Sand Point Way NE, Seattle, Washington 98115, U.S.A. E-mail: [email protected]Search for more papers by this authorAnne E. York, Anne E. York P. O. Box 31375, Seattle, Washington 98103, U.S.A.Search for more papers by this author Rod G. Towell, Rod G. Towell National Marine Mammal Laboratory, Alaska Fisheries Science Center, 7600 Sand Point Way NE, Seattle, Washington 98115, U.S.A. E-mail: [email protected]Search for more papers by this authorRolf R. Ream, Rolf R. Ream National Marine Mammal Laboratory, Alaska Fisheries Science Center, 7600 Sand Point Way NE, Seattle, Washington 98115, U.S.A. E-mail: [email protected]Search for more papers by this authorAnne E. York, Anne E. York P. O. Box 31375, Seattle, Washington 98103, U.S.A.Search for more papers by this author First published: 17 January 2006 https://doi.org/10.1111/j.1748-7692.2006.00026.xCitations: 68Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume22, Issue2April 2006Pages 486-491 RelatedInformation

An oil pipeline and its surrounding seafloor, located in the Santa Barbara Channel, southern California, were surveyed for fishes using a manned research submersible. The parts of the pipeline and seafloor surveyed were situated in waters 95-235 m deep. Some sections of the surveyed pipe were covered with both sessile and motile invertebrates, such as sea anemones (Metridium cf. farcimen) and sea urchins (Allocentrotus fragilis), sea stars (particularly Hippasteria cf. spinosa and Stylasterias cf. forreri), basket stars (Gorgonocephalus eucnemis), spot prawns (Pandalus platyceros), and king crabs (Paralithodes californiensis). Based on differences in fish assemblages, four habitats (shallow and deep pipeline and shallow and deep seafloor) were categorized. Fish densities along the shallow portion of the pipeline were about seven times higher than on the adjacent seafloor and densities along the deep pipeline portion were nearly six times that of the deeper seafloor. Along the pipeline, rockfishes comprised 84% of the fishes and included 22 species. Unidentified sanddabs (probably most or all Citharichthys sordidus), forming 33.2%, and combfishes (Zaniolepis frenata and Z. latipinnis), comprising 19% of the total, were most often observed on the seafloor. Most of the fishes living on the pipeline were either juveniles of such larger taxa as blackgill (Sebastes melanostomus), flag (S. rubrivinctus), and vermilion (S. miniatus) rockfishes, cowcod (S. levis), and lingcod (Ophiodon elongatus), or diminutive species such as halfbanded (S. semicinctus) and stripetail (S. saxicola) rockfishes, combfishes (Zaniolepis spp.), and poachers (Family Agonidae). Higher densities of fishes were often noted in areas of the pipeline that had been undercut. Of particular interest were the relatively high densities of juvenile cowcod along the deeper parts of the pipeline, densities that were far higher than any seen at over 80 natural outcrops and at ten platforms. We suggest that, in the process leading to oil platform and pipeline decommissioning, it is important to understand the role that human-made structure plays as fish habitat.

Stable isotope (615N and 6°C) values of individual tooth annuli of female Steller sea lions (n = 120) collected from the 1960s through the 1980s were used for retrospective analyses of temporal changes in food webs in the Gulf of Alaska and North Pacific Ocean. We also examined isotopically contour feathers of tufted puffins (n = 135) and crested auklets (n = 37) through this period to test for broader isotopic patterns indicative of whole food web changes. Steller sea lions decreased slightly in 6I3C and increased in 6”N values, suggesting an increasing trophic level and change in foraging location or oceanographic isotopic signature. Steller sea lion first and second tooth annuli were enriched in 15N and depleted in 13C compared with subsequent annuli, indicating the effects of maternal influence through weaning. The general pattern of increasing 615N values among Steller sea lions supports previous conclusions regarding a reduction or redistribution of forage fishes and an increase of demersal and semi-demersal species in the North Pacific ecosystem. There were no significant changes in 6I5N values for either bird species. However, 6I3C values in both bird species again suggested changes in foraging location or a shift in oceanographic currents.

The Steller's sea lion population has declined by 60%-70% over much of Alaska since the late 1970s. Overlap in species composition and sizes of fishes consumed by sea lions and harvested by commercial fisheries, particularly during winter, has led to examination of potential interaction between commercial fisheries and Steller's sea lions. Abundance and distribution data for Steller's sea lions in Alaska were derived from aerial surveys conducted during the breeding season, mid-June to early July 1992, 1994, and 1996. To study winter distribution of sea lions, we conducted aerial surveys during March 1993, November-December 1994, and March 1999. We counted about one-half as many sea lions during winter surveys compared to the breeding-season surveys. Numbers of sea lions at rookery sites dropped off considerably during winter, whereas numbers at haul-out sites did not. We found little evidence of large-scale, seasonal movement, at least for the western stock of sea lions. Rather, differences between summer and winter distribution were primarily a function of sea lions dispersing to local haul-out sites during the winter. Terrestrial sites, both rookeries and haul-outs, clearly are important to Steller's sea lions during the entire year. Individual sites may be occupied year-round or only during particular times of year.

A delayed response to change is often a characteristic of long-lived species and presents a major challenge to monitoring their status. However, rapid shifts in age structure can occur even while population size remains relatively static. We used time-varying matrix models to study age-structure information as a tool for improving detection of survivorship and fecundity change and status. We applied the methods to Steller sea lions (Eumetopias jubatus), a long-lived endangered marine mammal found throughout the North Pacific Rim. Population and newborn counts were supplemented with information on the fraction of the population that was juvenile, obtained by measuring animals in aerial photographs taken during range-wide censuses. By fitting the model to 1976-1998 data, we obtained maximum-likelihood estimates and 95% confidence intervals for juvenile survivorship, adult survivorship, and adult fecundity in the mid-1980s, late 1980s, and 1990s. We used a series of nested models to test whether the data were best fit by a model with one, two, or three temporal changes in demographic rates, and we fit the models to different lengths of data to test the number of years of data needed to detect a demographic change. The declines in the early 1980s were associated with severely low juvenile survivorship, whereas declines in the 1990s were associated with disproportionately low fecundity. We repeated these analyses, fitting only to the count data without the juvenile-fraction information, to determine whether the age-structure information changed the conclusions and/or changed the certainty and speed with which demographic-rate changes could be detected. The juvenile-fraction data substantially improved the degree to which estimates from the model were consistent with field data and significantly improved the speed and certainty with which changes in demographic rates were detected.

Understanding the ontogenetic relationship between juvenile Steller sea lions (Eumetopias jubatus) and their foraging habitat is key to understanding their relationship to available prey and ultimately their survival. We summarize dive and movement data from 13 young-of-the-year (YOY) and 12 yearling Steller sea lions equipped with satellite dive recorders in the Gulf of Alaska and Aleutian Islands (n=18), and Washington (n=7) from 1994 to 2000. A total of 1413 d of transmission (x =56.5 d, range: 14.5–104.1 d) were received. We recorded 222,073 dives, which had a mean depth of 18.4 m (range of means: 5.8−67.9 m; SD=16.4). Alaska YOY dived for shorter periods and at shallower depths (mean depth=7.7 m, mean duration=0.8 min, mean maximum depth=25.7 m, and maximum depth=252 m) than Alaska yearlings (x =16.6 m, 0=1.1 min, x = 63.4 m, 288 m), whereas Washington yearlings dived the longest and deepest (mean depth=39.4 m, mean duration=1.8 min, mean maximum depth=144.5 m, and maximum depth=328 m). Mean distance for 564 measured trips was 16.6 km; for sea lions ≤10 months of age, trip distance (7.0 km) was significantly less than for those >10 months of age (24.6 km). Mean trip duration for 10 of the 25 sea lions was 12.1 h; for sea lions ≤10 months of age, trip duration was 7.5 h and 18.1 h for those >10 months of age. We identified three movements types: long-range trips (>15 km and >20 h), short-range trips (<15 km and <20 h) during which the animals left and returned to the same site, and transits to other haul-out sites. Long-range trips started around 9 months of age and occurred most frequently around the assumed time of weaning, whereas short-range trips happened almost daily (0.9 trips/day, n=426 trips). Transits began as early as 7 months of age, occurred more often after 9 months of age, and ranged between 6.5 and 454 km. The change in dive characteristics coincided with the assumed onset of weaning. These yearling sea lion movement patterns and dive characteristics suggest that immature Steller sea lions are as capable of making the same types of movements as adults.