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BOX 5-1 Hormone replacement therapy (HRT), already in widespread use primarily to reduce the risk of osteoporosis, gained much attention, and some notoriety, when one of the studies in the Women s Health Initiative (WHI) was halted in 2002 The National Institutes of Health (NIH) National Heart, Lung, and Blood Institute (NHLBI) halted the Prempro phase (HRT phase) of the WHI during the summer of 2002 because of a higher than expected rise in breast cancer, heart attacks, strokes, and blood clots in the legs among this cohort as well as the failure of the expected bene ts to materialize The two studies consisted of an HRT phase, estrogen plus progestin in women with a uterus, and the estrogen replacement therapy (ERT) phase in women without a uterus HRT is sometimes recommended for women who have undergone natural menopause; ERT is more appropriate for women whose menopause is surgically-induced The ERT phase of the WHI ended in 2006 Follow-up of the women in both studies is scheduled to conclude in 2010 Over 16,000 women were randomized in the HRT phase to estrogen + progestin or placebo and approximately 10,000 women in the ERT phase were likewise randomized to estrogen or placebo Few of the participants were taking HRT (13% in the HRT cohort and 6% in the ERT cohort), though the numbers that had ever used HRT were three-fold higher It has been suggested that the results of these studies are not generalizable to premenopausal/perimenopausal women, who are more likely to be experiencing menopausal symptoms, because many of the women in the study may not have been experiencing menopausal symptoms any longer Women should decide on the appropriateness of HRT or ERT therapy in medical consultation based on the individual s speci c risk factors and medical pro le See the NIH Web site (http://wwwnhlbinihgov/health/women/pht_factspdf) for more information.

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Involving teams in process mapping As in basic flowcharting, it is essential to have both experienced and novice employees physically follow the work as it flows from activity to activity Those who are familiar with the process can provide a jump start to the mapping process However, experienced people sometimes miss the obvious because they are too familiar with the process It is the team members who are not familiar with the process and have to learn it from scratch who will most likely ask the simple questions that lead to great discoveries such as hidden steps that are implicitly assumed but undocumented and non-value-add

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women25 The use of topical estrogen has been shown to increase epidermal thickness in postmenopausal women26,27 However, whether the beneficial effects of estrogen on skin dryness are attributable to its influence on the fibroblast and an increase in hyaluronic acid content, with the concomitant increase in waterretaining capacity of the dermis, or a direct effect of estrogen on the epidermis remains unclear While the number of sebaceous glands remains the same during life, as androgen levels decline with advanced age, sebum levels tend to decrease28 Although the level of surface lipids falls with age owing to decreased sebaceous gland function, paradoxically the sebaceous glands become larger, rather than smaller, as a result of decreased cellular turnover28 Subcutaneous fat is also important when it comes to maintaining the appearance of youth, and fat distribution is another area where sex hormones play a vital role In postmenopausal women, the decrease in estrogen and the unmasking effects of systemic androgens lead to central fat accumulation In a study by Dieudonne et al examining androgen receptors in mature human adipocytes, androgen binding sites were found to differ by location, with twice as many androgen binding sites in intra-abdominal fat than in subcutaneous fat29 This finding was the same for fat deposits in men and women29 Another study by Dieudonne et al investigating the location of estrogen receptors in mature human adipocytes of both men and women found that the predominant estrogen receptor was ER- and that its level of expression was the same regardless of origin (intra-abdominal or subcutaneous fat)30 These results suggest that the deposition of subcutaneous fat is mainly influenced by estrogen, while the deposition of abdominal fat is more androgendependent

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10 Strategic, Functional, or Noncore classification: The overall process may fall into one category, while steps within the process may fall into another As you look at each activity in the process, you will classify the activity as value-add or non-value-add For example, a call center that is spending half its time with irate customers is 50% non-value-add; the upstream process must be fixed A warehouse is all non-value-add; something upstream is causing this cost

With the proper data in hand, the CVSM gives you a clear indication of the process cycle time through the entire process, as well as in subcomponents of the process Adding this data to the basic flow map results in a diagram like that shown in Figure 712 (below)

Intuitively, for each sailor we check that there is no boat that has not been reserved by this sailor

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