Hormones,Mood and Sexuality across the Lifespan

From menstruation to menopause, both biologically and psychologically, this symposium brought international experts together to celebrate the life work in women's health by Professor Lorraine Dennerstein, who retires as Director of the Office of Gender and Health, University of Melbourne (Melbourne, Australia) after 30 years. All those presenting, from the USA, Italy, Belgium, Norway and Australia, have worked with Lorraine and present international perspectives on an area where she was one of the pioneers. Included are latest research and clinical understanding of premenstrual disorders, perinatal depression and menopausal transition, including mood, physical and cognitive changes, effect on the skeleton and the role of hormones.

This festschrift took the participant through an update of clinical issues for women through their reproductive life. John Randolph from the University of Michigan (MI, USA) began, setting the stage for the rest of the day, by relating reproductive physiology with behavior. He highlighted Dennerstein's work as a driving force in transforming the ill-defined domain of women's health into a recognized field of study, first with her work on oral contraceptives and sexuality, following through the early 1970s with the increasingly clear data linking affect to the menstrual cycle, and into the 1980s when she established that, rather than abnormal levels of hormones in those who suffered cyclically, it was an abnormal response to normal cyclic changes that characterized premenstrual syndrome (PMS).

Jeanne Leventhal Alexander (Director of Psychiatry and Women's Health, Kaiser Permanente Northern California, Alexander Foundation for Women's Health, CA, USA) discussed PMS and premenstrual dysphoric disorder (PMDD) further, discussing the effect of the woman with PMDD having a ‘vulnerable brain’ to depression and the roles that PMS and PMDD play as risks for a symptomatic menopausal transition.

The other time of great hormonal change and increased mental health risk – the perinatal period – was summarized by myself. Dennerstein, herself a psychiatrist (although from the array of her collaborator' backgrounds this could easily come as a surprise), was responsible for the first two mother–baby units in Australia. Victoria still has the highest number per head of inpatient mother–baby psychiatric beds in the world – one at Larundel Hospital, established in 1983 with Burrows, and the second at the Mercy Hospital for Women, established in 1989 – when I began working with her. From her risk factor' research across three continents in 1989, we have now progressed to the largest screening study funded by beyondblue, which assessed over 40,000 women. This found that 16% of women suffer from depression and anxiety perinatally, ranging from 5 to 25% depending on region. Risk factors include past and family history of affective disorder, lack of support, multiple stresses, low socioeconomic background, and history of abuse. The importance of early identification and intervention was highlighted in light of research that shows that infants of depressed mothers are at higher risk of emotional and cognitive difficulties. This risk appears to begin antenatally, with the infant exposed to a maternal heightened hypothalamic–pituitary–adrenal axis, which affects its own regulatory abilities. Subsequent exposure to insensitive or over-intrusive, anxious parenting through its affect on attachment, itself intergenerational, then puts the child at greater risk of mental illness in child-and adult-hood.

Bronwyn Stuckey from the Keogh Institute (Nedlands, WA) highlighted the issues of hormones and sexuality in the reproductive years. Sexual interest decreases with age, but distress regarding this also decreases in parallel. Hormonal changes over the menstrual cycle correlate with higher interest in the follicular phase and a luteal phase decline. The impact of the oral contraceptive on sexual drive varies according to different studies, the main reason being the interaction between biological, motivational and relational factors in the choice and compliance. The role of androgens, either in etiology or therapy, remains controversial.

Henry Burger from Prince Henry's Institute, Monash Medical Centre (Melbourne, Australia), who has worked with Dennerstein on her extensive Midlife project, began the section on menopausal transition with their endocrinological findings from women at this time. The huge variability in the hormone levels –considered complex, variable and unpredictable – led him to recommend that measurements were largely unhelpful and diagnosis of menopausal status was best done on history.

Four other presentations looked at the menopausal transition. Sioban Harlow (University of Michigan) took up Burger's point and looked at how to define the transition, relating the findings of STRAW (Stages of Reproductive Aging Workshop) in 2001, an international group that staged perimenopause and postmenopause into an early and late stage for each, followed by the ReSTAGE collaboration, which evaluated which was the most valid, robust and replicable of the criteria and concluded that for late menopausal transition, 60 days of amenorrhea was accurate in 68% of women.

Janet Guthrie (Melbourne) presented on the mood component of the Melbourne Midlife project, which suggested that neither age nor menopause in itself were associated with an increase in depression, and whilst a history of hormonal sensitivity might make someone more vulnerable, other factors such as physical health, stress and not having a partner were also important. Another myth that was challenged was that of the empty nest: women had less depression and a more positive mood when children left – but this reversed were they to return!

Philippe Lehert (Belgium), abiostatistician collaborating on the Midlife project (after the first collaboration on the postnatal depression work some years earlier), brought to life a complex analysis of the Midlife project, and was able to determine the parameters of hormone change that contribute to the level of vasomotor and sexual symptoms.

Alessandra Graziottin (Italy) finished this session with a snapshot of the couple going through menopause and the issues that aging brought up for both. She reviewed the evidence that, in line with Dennerstein's pioneering research, indicated that feelings for one's partner and partner's general health and sexual problems had a greater effect than hormones in modulating the sexual changes that women report during the menopausal transition. Indeed, female sexual dysfunctions can be precipitated or worsened by ongoing erectile difficulties in their partner. However, hormones do have a role: vaginal dryness, secondary to the menopausal hormone' loss, may not only contribute to loss of the woman's desire, due to the negative feedback from the genitals, but may also contribute to precipitate the erectile dysfunction, in a vicious circle that can make sexual intimacy increasingly problematic for both partners. However, therapy with phosphodiesterase type 5 inhibitors has proven significantly effective in improving sexual wellbeing in the female partner. Looking at the couple as a sexual dyad is essential to optimize the diagnosis and treatment of sexual dysfunction(s) in both partners at midlife and beyond.

The final presentations looked at the postmenopausal woman. Victor Henderson (Stanford University, CA, USA) examined midlife estrogen exposures and cognitive change from the perspective of the Melbourne Women's Midlife Project and other studies. Despite some conflicting results, there is no convincing evidence that the natural menopause or use of hormone therapy has a substantial effect on memory during the years encompassing the menopausal transition and early postmenopause. Long-term effects of midlife estrogen exposures on Alzheimer's disease risk and other cognitive outcomes remain to be clarified.

Pauline Maki (University of Illinois, IL, USA) discussed her neuroimaging research, looking at the mechanisms by which hormone therapy might improve memory function when given early in the menopause, particularly by altering hippocampal function. More research is needed to elucidate how hormone therapy, when administered early in the menopausal transition, might alter neural systems related to memory function.

Berit Schei (Norway) finished the extraordinarily rich program with a discussion of the burden of osteoporosis, where Norway has amongst the highest rates in the world. Early detection and prevention with increased physical activity – and not being too thin –appear to be the best ways of managing to date.

This festschrift brought together an array of international speakers with an enormous breadth of knowledge, from clinical and research perspectives, of women's health and hormones. The backgrounds of speakers ranging from psychiatrists to biostatisticians and gynecologists are a testimony to the extraordinary capacity of Dennerstein to look broadly at issues and bring people together. The richness of the day came not just from the speakers individually, but also from what they did together in honoring the woman who for many was a mentor, for others a friend.

Future perspective

While it is clear that there has been much progress in women's health, there is much in the complexity of hormones and how they link to mood and memory that is still to be clarified. Future research needs to look in particular at improving synthetic hormones and our ability to use them effectively.

Highlights

• The brain is made vulnerable by many factors; for some women, hormonal sensitivity leaves them at risk of mood disturbance.

• Prevention plays an increasing role: for osteoporosis, for psychological management of the perimenopause and for infants of those women with depression.