There has been limited longitudinal research in hot flashes and related menopausal symptoms in cancer that defines when the most problematic symptoms begin, which women experience hot flashes the longest and what the predictors of response to various treatments are. In one cross sectional internet based survey of women who were diagnosed with breast cancer at 40 years of age or younger, cognitive symptoms were more prevalent than hot flashes. Of 371 women with a mean age of 33, 81 % of the sample reported forgetfulness as a bothersome symptom, 72 % concentration difficulties, 71 % distractability and 46 % reported bothersome hot flashes, using the Breast Cancer Prevention Treatment Checklist to measure symptoms (Leining et al. 2006). In contrast, in an earlier longitudinal European treatment trial where women were randomized to high dose versus conventional chemotherapy (Malinovszky et al. 2006), both groups of women reported increases in night sweats and hot flashes throughout the first year, maintaining high levels of those symptoms throughout the 5 years of follow up. A second longitudinal study followed women on the NSABP B-30 trial for 24 months. Vasomotor symptoms (hot flashes, night sweats and cold sweats) were common in both women who had stopped menses and those who continued menstruating. As early as day 1 of cycle 4 of chemotherapy, 74 % of women reported hot flashes. At 6 months, 85 % of women who were amenorrheic and 89 % of those who were still menstruating, reported vasomotor symptoms. At 12 months, of the women who ceased menses, 90 % reported symptoms and of those who were menstruating, 55 % reported vasomotor symptoms (Swain et al. 2009). Research indicates that hot flashes begin during chemotherapy and increase and continue throughout 2 years of follow up (Barton et al. 2009).

Pharmacologic treatment with estrogen has been a common treatment for healthy women, but that may not be a safe option in women who have a history of breast cancer. During the 1990s, in the period before the results of the Women’s Health Initiative hormone trials, bothersome hot flashes were perceived as another trauma of the cancer diagnosis, since women with breast cancer were being denied a therapy that was routinely recommended in healthy mid-life women. Thus, there was a strong sense of urgency to find alternative strategies to manage hot flashes in breast cancer patients and survivors (Loprinzi et al. 2008). Serendipitous findings, and rigorous placebo controlled clinical trials, demonstrated the treatment benefits of serotonin reuptake inhibitor antidepressants and gabapentin for hot flash relief (Loprinzi et al. 2008, 2009; Barton and Loprinzi 2004). Subsequent mechanistic studies related to these agents have been pursued. These agents now have the strongest evidence to date for non-hormonal treatment of hot flashes.

None of these non-hormonal agents, though, have reduced hot flashes beyond about 60 %. Further, pharmacologic treatments are wrought with unwanted side effects or unwanted stigma. Many times women do not want to take an antidepressant and women who have gone through treatment for breast cancer often do not want to take “yet another pill,” as taking medication is reminiscent of “being ill”. Research has also not provided insight into who does or does not respond to various antidepressant therapies. It is hypothesized that serotonin is the active ingredient in antidepressants for the amelioration of hot flashes but this has not been proven and there is less known about why gabapentin helps hot flashes. One thing that has been clearly proven with the hot flash research is that neither the population (naturally menopausal, chemotherapy induced or surgically induced) nor the hot flash etiology (tamoxifen, aromatase inhibitors, or just menopausal status) has differentially impacted response to the evidence-based treatments to date (Loprinzi et al. 2008; Bardia et al. 2009).

Mind-body, psycho-educational and cognitive-behavioral interventions have also been studied. These intervention modalities are interesting as they represent ways for women to self-manage and also have little in the way of unwanted side effects. Unfortunately, the evidence is mixed with regard to these behaviorally based therapies and are plagued by small sample sizes, poor effect sizes and lack of appropriate control groups. Recent randomized trials have evaluated cognitive behavioral therapy (CBT) for hot flashes, and at least three have been done in women with breast cancer. Most of these interventions have utilized a combination of cognitive and behavioral approaches, most commonly, paced breathing and relaxation, education about menopause, cognitive strategies to address negative thinking or attitudes and catastrophizing, and behaviors to improve sleep and manage stress and anxiety (Ayers et al. 2012; Duijts et al. 2012; Mann et al. 2012; Tremblay et al. 2008; Balabanovic et al. 2012). Many of the studies have used usual care or “no treatment” control groups. In addition, some of the studies used a support group approach to deliver the intervention, while others used one on one time with clinical psychologists and/or social workers. The intervention time was often 90 min for 6 weeks. Most of these studies have demonstrated improvements in the distress and bother related to hot flashes , but not the number or severity of hot flashes themselves (Ayers et al. 2012; Duijts et al. 2012; Mann et al. 2012; Tremblay et al. 2008; Balabanovic et al. 2012). One study, using a cognitive behavioral intervention for hot flashes in women with breast cancer, included a qualitative interview to learn about women’s perception of the effect of the intervention on their symptoms (Balabanovic et al. 2012). Women talked about having a different attitude toward their symptoms, coping better, feeling distracted from their symptoms, and gaining control over their lives. They also talked about the importance of the group support. This study provides some insight into the elements of a cognitive behavioral intervention that may be more important in achieving wanted results. Interestingly, to date, there has been little research done to capitalize upon the potential synergy or additive effect of non-pharmacologic and pharmacologic therapies in such a way as to essentially eliminate side effects while improving effects.

Pharmacologic research for hot flash control has demonstrated a placebo effect of about 25–30 %, but this varies across studies (Loprinzi et al. 2008; Bardia et al. 2009). The mechanism by which the placebo improves hot flashes has not been investigated and would provide insight. It is important, though, to include an appropriate control group when evaluating interventions for hot flashes and related menopausal symptoms. It could be said that there is a placebo effect in much of symptom research, which makes appropriate control groups necessary, even in behavioral research, in order to understand the benefit of the intervention evaluated.

In summary, much of the research in hot flashes has been narrowly focused and has neither addressed menopausal symptoms broadly nor incorporated complementary mechanistic approaches (pharmacologic with behavioral). Research is needed to address relationships between symptoms and respective responses to tailored treatment.

There is a surprising amount of research in sexual health that encompasses descriptive studies, psychological interventions for overall sexual health and pharmacologic interventions for vaginal symptoms. Much of the research in this area, however, suffers from small sample sizes, small effect sizes and a lack of control groups to account for non-specific effects of group and provider interactions. Most studies focus on three groups of survivors, breast, gynecologic and prostate cancer (Brotto et al. 2010; Taylor et al. 2011). In cancer survivors, sexual health research is largely represented by cross-sectional studies or very small longitudinal research. What is known about sexual health in women with breast cancer is that, in age matched studies, women with breast cancer report worse functioning (Howard-Anderson et al. 2012; Basson 2010; Speer et al. 2005) and that women who have undergone treatment for breast cancer (including surgery, tamoxifen or chemotherapy) report more sexual concerns than those women with breast cancer who have not had these treatments (Gilbert et al. 2010). Women who are younger and those with more advanced disease may experience the most disruption of their sexual health (Andersen et al. 2007). Though sexual health may decline during treatment, there is some improvement gradually when treatment ends, but data do not support that function returns to baseline levels (Krychman and Millheiser 2013). However, it is not known in which individuals function returns to baseline and for whom concerns persist or even increase. The prevalence of sexual health concerns in published data ranges from 30 to 100 % (Speer et al. 2005; Gilbert et al. 2010; Andersen et al. 2007; Burwell et al. 2006; Krychman and Millheiser 2013; Biglia et al. 2010) and generally consists of problems with lubrication, dyspareunia, desire, body image and relationship concerns (Burwell et al. 2006). Like other symptoms, such as fatigue where research is growing to provide new insights, sexual health concerns may be more pervasive, start earlier, and last longer than we currently know.

One source of evidence is a longitudinal study in 35 premenopausal women diagnosed with breast cancer (Biglia et al. 2010). These women reported below normal sexual activity on the McCoy Female Sexual Questionnaire, as early as their first post-surgical visit. Sexual scores decreased further during chemotherapy and even further one year later. Specific areas which were negatively impacted included activity, desire, arousability, quality of partner relationship and body image (Biglia et al. 2010). On the other end of the spectrum of study sizes, a survey study of breast cancer survivors (N = 1,134) had participants complete self-report questionnaires to identify variables that predicted sexual health (Ganz et al. 1999). Predictors of sexual interest included body image and mental health, as well as having a new partner since being diagnosed, and predictors of decreased sexual function included vaginal dryness, past chemotherapy, and having a new partner since being diagnosed (Ganz et al. 1999).

A comprehensive review of the literature between 1998 and 2010 summarizes the breadth and complexity of the issues surrounding sexual health in women after a diagnosis of breast cancer. The list includes sexual function disturbances (arousal, lubrication, orgasm, desire and pleasure), but also lists psychological issues of negative body image, feeling sexually unattractive, loss of femininity, anxiety, depression and changes in one’s sense of sexual self (Gilbert et al. 2010). Likewise, a meta-synthesis of 30 qualitative studies, representing 795 women, supports the concepts of “redefining self” in terms of body image and womanhood/femaleness as a pervasive, critical issue in sexual health and functioning in women with breast cancer (Bertero and Chamberlain Wilmoth 2007). Estimates of the prevalence of body image concerns range from 31 to 67 %, and the prevalence of those reporting arousal or interest issues is 46 to 56 %, respectively (Fobair and Spiegel 2009).

Thought provoking results emanate from one European longitudinal study (Malinovszky et al. 2006). Three hundred ninety women randomized to conventional or high dose chemotherapy for high risk, node positive breast cancer completed the sexual activity questionnaire at baseline, after surgery but before treatment, at 6 and 12 months and yearly out to 5 years. Despite the findings that vaginal dryness and dyspareunia occurred during the first year and persisted throughout the 5 years and significantly increased compared to baseline, the numbers of women who engaged in sexual activity and the frequency of sexual activity did not significantly change from 12 months and beyond. Pleasure was also significantly lower at every time point, when compared to baseline. This was not significantly different based on high dose or conventional dose chemotherapy (Malinovszky et al. 2006). Therefore, women in this study were engaging in behavior that was increasingly difficult and unpleasant, suggesting a critical need for research to address this unmet need.

It is important to note that intervention research in sexual health in the general population cannot likely be extrapolated to the cancer population, which is admittedly different than the research on hot flashes. This lesson is demonstrated by the fact that there are 11 positive randomized controlled trials of transdermal testosterone in various non-cancer populations of women for improving libido (Davis et al. 2006, 2008a, b; Goldstat et al. 2003; Shifren et al. 2000, 2006; Simon et al. 2005; Braunstein et al. 2005; Buster et al. 2005; Nathorst-Boos et al. 2006; Chudakov et al. 2007) while the one large study that evaluated transdermal testosterone in female cancer survivors was decidedly negative (Barton et al. 2007b). Interestingly, the lack of benefit was seen despite similar testosterone doses and improvement in testosterone concentrations for the intervention group (Barton et al. 2007b). This may be because women who have chemotherapy induced menopause are hormonally depleted more severely and more broadly than the women on these positive trials. In fact, in one subanalysis, women who had had bilateral oophorectomies did not experience the same benefit in the primary outcome of sexually satisfying events as women who had were naturally postmenopausal (Davis et al. 2008b), thus supporting the idea that the degree to which hormones are depleted makes a difference in outcomes.

Though there are studies that provide evidence of the areas of sexual health that are negatively impacted as a result of the cancer experience, there is little research that teases out specific predictors in subgroups of women longitudinally. There is even less research evaluating comprehensive interventions to address the complexities of sexual health. One early and important study in this area, that was clearly ahead of its time, was (Ganz et al. 2000; Zibecchi et al. 2003) a comprehensive menopausal assessment intervention. The intervention was developed to address three symptoms (hot flashes, vaginal dryness and urinary incontinence). An advanced practice nurse assessed each woman’s needs and developed a tailored intervention, including pharmacologic and behavioral interventions for these three main issues. At the time of the study, there were not extremely effective interventions for any of these problems. Despite this, the investigators reported significant improvements in sexual health as measured by the sexual summary scale from the Cancer Rehabilitation Evaluation System (CARES) over the usual care control group. This significant improvement was still present at the 2 month follow up.

There is a fair amount of research on psychological interventions for sexual health (Brotto et al. 2010; Taylor et al. 2011). These studies are designed to deliver the interventions mostly in person, but at least one tested a telephone intervention (Salonen et al. 2009). The content of the psychological interventions included education about managing symptoms and distress related to symptoms and body image changes, behaviors to improve sexual response, communication skills and, where couples were involved, how to cope as a couple (Brotto et al. 2010; Taylor et al. 2011). Physical exercise was also often included (Taylor et al. 2011). Yet, research has not been done to identify and build on the most effective strategies for sexual health, nor has much of this research been appropriately controlled for non-specific, provider or group effects.

For vaginal symptoms, some research has focused on evaluating the lowest dose of estrogen that has the potential to improve symptoms of dryness and dyspareunia without impacting systemic estradiol concentrations (Krychman and Millheiser 2013; Tan et al. 2012; Goldfarb et al. 2013). There has been little research that has taken a systematic approach to addressing the multiple etiologies that contribute to decreases in sexual health. In addition, the research in this area appears disparate, without evidence of an attempt to build on and expand on previous findings. Hence, more research is needed to clarify the etiologies of various aspects of sexual health changes after cancer and intervention research should be individualized to target more than one aspect of this problem.