Endocrine Society of Australia position statement on male hypogonadism (part 2): treatment and therapeutic considerations.

Introduction: Part 1 of this position statement dealt with the assessment of male hypogonadism, including the indications for testosterone therapy. This article, Part 2, focuses on treatment and therapeutic considerations for male hypogonadism and identifies key questions for future research.

Main Recommendations: Key points and recommendations are:Excess cardiovascular events have been reported in some but not all studies of older men without pathological hypogonadism who were given testosterone treatment.

Endocrine Society of Australia position statement on male hypogonadism (part 1): assessment and indications for testosterone therapy.

Introduction: This article, Part 1 of the Endocrine Society of Australia's position statement on male hypogonadism, focuses on assessment of male hypogonadism, including the indications for testosterone therapy. (Part 2 will deal with treatment and therapeutic considerations.)

Main Recommendations: Key points and recommendations are:Pathological hypogonadism arises due to diseases of the hypothalamus or pituitary gland (hypogonadotropic hypogonadism) or testes (hypergonadotropic hypogonadism).

Competency in menopause management: whither goest the internist?

Background: After publication of the Women's Health Initiative study in 2002, use of menopausal hormone therapy (HT) has declined by nearly 80% worldwide and internists now play only a limited role in menopause management. Over the past decade, new data have increased our knowledge of the multiple effects and mechanisms of HT.

Methods: Existing literature was reviewed.

The perimenopausal woman: endocrinology and management.

This review focuses on the endocrine and physiological features of the transition to menopause, known as the menopausal transition or the perimenopause. The updated 2011 Stages of Reproductive Aging workshop (STRAW) system is presented with a discussion of the new subdivisions within stages -3 (late reproductive age) and +1 (postmenopause) and incorporation of FSH and other biomarkers in the supportive criteria. Ovarian follicle reserve and ovarian follicle dynamics are also discussed in terms of the changes that occur with reproductive aging, and the dramatic effect these changes have on the hypothalamic-pituitary-gonadal feedback system.

Does hormone replacement therapy (HRT) cause breast cancer? An application of causal principles to three studies.

Background: Based principally on findings in three studies, the Collaborative Reanalysis (CR), the Women's Health Initiative (WHI), and the Million Women Study, it is claimed that hormone replacement therapy (HRT) is an established cause of breast cancer. The authors have previously reviewed those studies (Parts 1-4). The WHI findings were first published in 2002, following which the use of HRT rapidly declined.

Vitex agnus-castus extracts for female reproductive disorders: a systematic review of clinical trials.

Vitex agnus-castus L. (chaste tree; chasteberry) is a popular herbal treatment, predominantly used for a range of female reproductive conditions in Anglo-American and European practice. The objective of this systematic review was to evaluate the evidence for the efficacy and safety of Vitex extracts from randomised, controlled trials investigating women's health.

Does hormone replacement therapy cause breast cancer? An application of causal principles to three studies. Part 4: the Million Women Study.

Background: Based principally on findings in three studies, the collaborative reanalysis (CR), the Women's Health Initiative (WHI) and the Million Women Study (MWS), it is claimed that hormone replacement therapy (HRT) with estrogen plus progestogen (E+P) is now an established cause of breast cancer; the CR and MWS investigators claim that unopposed estrogen therapy (ET) also increases the risk, but to a lesser degree than does E+P. The authors have previously reviewed the findings in the CR and WHI (Parts 1-3).

Objective: To evaluate the evidence for causality in the MWS.

Unpredictable endocrinology of the menopause transition: clinical, diagnostic and management implications.

The approach to menopause can be divided into the early (E) and late (L) menopausal transitions (MT) on the basis of menstrual irregularity (EMT) and subsequent observation of at least one episode of 60 or more days amenorrhoea (LMT). In total, 40-60% of cycles in the LMT are anovulatory, often with low oestradiol (E2) and high follicle-stimulating hormone concentrations. The ovulatory cycles have variable endocrine characteristics, none of which is specific to EMT or LMT.

A randomized study of the effect of mifepristone alone or in conjunction with ethinyl estradiol on ovarian function in women using the etonogestrel-releasing subdermal implant, Implanon®.

Background: Mifepristone alone or in combination with ethinyl estradiol (EE) can effectively stop an episode of uterine bleeding in women using the etonogestrel-releasing contraceptive implant, Implanon® but could impair contraceptive efficacy.

Aim: To examine the effects of administration of mifepristone alone or with EE on ovarian function and cervical mucus consistency in women using Implanon.

Study Design: Women using Implanon were randomized to mifepristone 25 mg twice daily on day 1 plus placebo 1 daily for 4 days or plus EE 20 mcg daily for days 2-5.

Changes in serum antimüllerian hormone levels across the ovulatory menstrual cycle in late reproductive age.

Objective: The aim of this study was to assess the pattern of serum antimüllerian hormone (AMH) across the normal ovulatory menstrual cycle in women in late reproductive age when ovarian follicle reserve and, hence, serum AMH levels are reduced.

Methods: Serum AMH levels were determined by enzyme-linked immunosorbent assay across the ovulatory menstrual cycle from women in mid (n = 18) and late (n = 43) reproductive life, including the menopausal transition.

Result: : No intracycle variation in AMH level was observed in women in mid reproductive life nor in 33% (n = 14) of women with normal ovulatory cycles in late reproductive age.

Postmenopausal hormone therapy: an Endocrine Society scientific statement.

Objective: Our objective was to provide a scholarly review of the published literature on menopausal hormonal therapy (MHT), make scientifically valid assessments of the available data, and grade the level of evidence available for each clinically important endpoint. PARTICIPANTS IN DEVELOPMENT OF SCIENTIFIC STATEMENT: The 12-member Scientific Statement Task Force of The Endocrine Society selected the leader of the statement development group (R.J.

Effects of a combination of Hypericum perforatum and Vitex agnus-castus on PMS-like symptoms in late-perimenopausal women: findings from a subpopulation analysis.

Background: It has been suggested that some of the symptoms typically attributed to menopause may be more related to premenstrual syndrome (PMS) than menopause, as perimenopausal women appear to be more prone to PMS-like symptoms, or at least to tolerate them less well.

Objective: The objective of this study was to evaluate the effectiveness of a phytotherapeutic intervention comprising a combination of Hypericum perforatum (St. John's wort) and Vitex agnus-castus (chaste tree/berry) in the management of PMS-like symptoms in perimenopausal women.

Vitex agnus-castus (Chaste-Tree/Berry) in the treatment of menopause-related complaints.

Background: The origin of the current practice of administering Vitex agnus-castus in menopause-related complaints is uncertain, but appears to be relatively recent. Here we review the evidence for this application of Vitex based on evidence from pharmacological studies and clinical research.

Methods: The mechanisms of potential relevance in the context of menopause are explored with reference to the current understanding of the endocrinology and neuroendocrinology of menopause and associated symptoms.

Predictors of placebo response in a randomized, controlled trial of phytotherapy in menopause.

Objective: The aim of this study was to evaluate predictors of the placebo response in a randomized, placebo-controlled, double-blind trial of a phytotherapeutic combination for the treatment of menopausal symptoms.

Methods: A post hoc analysis was conducted on data from 46 placebo participants completing the study. Variables at baseline were investigated for prediction of improvement on any of the endpoints of flushing, depression measured on the Hamilton Depression Inventory, and menopausal symptoms measured on the Greene Climacteric Scale.

Are we drawing the right conclusions from randomised placebo-controlled trials? A post-hoc analysis of data from a randomised controlled trial.

Background: Assumptions underlying placebo controlled trials include that the placebo effect impacts on all study arms equally, and that treatment effects are additional to the placebo effect. However, these assumptions have recently been challenged, and different mechanisms may potentially be operating in the placebo and treatment arms. The objective of the current study was to explore the nature of placebo versus pharmacological effects by comparing predictors of the placebo response with predictors of the treatment response in a randomised, placebo-controlled trial of a phytotherapeutic combination for the treatment of menopausal symptoms.

A prospective study of the association between endogenous hormones and depressive symptoms in postmenopausal women.

Objective: Across a woman's lifetime, variations in hormone levels are known to influence mood and well-being. Whether absolute or changes in hormone levels over time are associated with depression among postmenopausal women remains unclear.

Methods: The Melbourne Women's Midlife Health Project is a longitudinal population-based study of women who were followed through the menopausal transition.

Atypical estradiol secretion and ovulation patterns caused by luteal out-of-phase (LOOP) events underlying irregular ovulatory menstrual cycles in the menopausal transition.

Objective: The menopausal transition is characterized by irregular menstrual cycles and unpredictable hormone levels, including dramatic swings in estradiol (E2). An increasing number of studies have found variable high E2 and low luteal phase progesterone occur with progression of Stages of Reproductive Aging Workshop (STRAW)stage, but the cause remains unclear. To explore the causes of the erratic changes in E2, individual within-cycle secretion patterns of E2, progesterone, follicle-stimulating hormone, luteinizing hormone, inhibin A, and inhibin B were explored in detail.

Interrelationships between ovarian and pituitary hormones in ovulatory menstrual cycles across reproductive age.

Context: Ovarian hormones regulate pituitary gonadotropin secretion across the menstrual cycle via negative and positive feedback mechanisms. The contribution of individual hormones is complex and is a continuing area of research.

Objective: The aim of the study was to identify relationships between LH/FSH and estradiol, progesterone, inhibin A, inhibin B, and anti-Mullerian hormone (AMH) in ovulatory menstrual cycles across reproductive age.

Hypericum perforatum with Vitex agnus-castus in menopausal symptoms: a randomized, controlled trial.

Objective: To evaluate the effectiveness of a phytotherapeutic intervention comprising a combination of Hypericum perforatum (St. John's wort) and Vitex agnus-castus (Chaste tree/berry) in the management of menopausal symptoms.

Design: A double-blind, randomized, placebo-controlled, parallel trial was performed over 16 weeks in 100 eligible late-perimenopausal or postmenopausal women experiencing hot flushes and other menopausal symptoms.

A proposed classification system for menstrual cycles in the menopause transition based on changes in serum hormone profiles.

Objective: To characterize menstrual cycles in women in late reproductive age and the menopause transition, based on changes in serum hormone levels.

Design: Serum levels of estradiol, progesterone, follicle-stimulating hormone (FSH), luteinizing hormone, inhibin A, inhibin B, and antimüllerian hormone, as previously reported as mean data grouped according to the Stages of Reproductive Aging Workshop proposals, were analyzed in 55 women aged 45 to 55 and compared with those in 21 women aged 21 to 35.

Results: The ovulatory cycles in the older women were divided into three types.

Cycle and hormone changes during perimenopause: the key role of ovarian function.

The menopausal transition is the stage in reproductive life commonly defined as commencing with the onset of menstrual irregularity. Classic studies of the endocrinology of the transition postulated the existence of inhibin in women to explain the observed increase in follicle-stimulating hormone (FSH) levels without a significant decrease in estradiol (E2). Descriptions were provided of cycle characteristics during the transition, emphasizing the unpredictability of the endocrine changes rather than the occurrence of an orderly and progressive decline in ovarian function.

New findings from non-linear longitudinal modelling of menopausal hormone changes.

Changes in FSH and estradiol (E2) across the menopausal transition are clearly not linear. The present study utilizes data from 204 women who completed the 13-year prospective Melbourne Women's Midlife Health Project. E2, FSH, symptoms, self-rated health, mood, sexual function and coronary heart disease (CHD) risk were measured longitudinally.

Endocrine features of menstrual cycles in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) staging system.

Context: Female reproductive aging based on changes in menstrual cycle length and frequency progresses through a number of stages as defined by the Stages of Reproductive Aging Workshop (STRAW) staging criteria.

Objective: This paper provides a comprehensive description of the endocrine features associated with the STRAW stages.

Design: Healthy women aged 21-35 and 45-55 yr submitted three blood samples a week over a single menstrual cycle.