Personal view: Hormones and depression in women.

Depression is more common in women, occurring at times of hormonal fluctuations as premenstrual depression, postnatal depression and perimenopausal depression. These are all related to changes in hormone levels and constitute the diagnosis of reproductive depression. There is a risk that severe premenstrual depression can be misdiagnosed as bipolar disorder and that women will be started on inappropriate antidepressants or mood-stabilizing therapy. The most effective treatment for severe premenstrual syndrome is by suppression of ovulation and suppression of the cyclical hormonal changes by transdermal estrogens or by GnRH analogs. Postnatal depression is more common in women with a history of premenstrual depression and also responds to transdermal estrogens. Transdermal testosterone gel can be also used in women who suffer loss of energy and loss of libido which may be due to the inappropriate prescription of antidepressants. There is also a role for the Mirena IUS and laparoscopic hysterectomy and oophorectomy in women who are progestogen-intolerant. The hormonal causation of certain common types of depression in women and the successful treatment by estrogens should be understood by psychiatrists and gynecologists.

The sonopartogram: a novel method for recording progress of labor by ultrasound.

OBJECTIVES: Progress of labor has hitherto been assessed by digital vaginal examination (VE). We introduce the concept of a non-intrusive ultrasound (US)-based assessment of labor progress (the 'sonopartogram') and investigate its feasibility for assessing cervical dilatation and fetal head descent and rotation. METHODS: This was a prospective study performed in 20 women in the first stage of labor in two European maternity units. Almost simultaneous assessment of cervical dilatation and fetal head descent and rotation were made by US and digital VE. RESULTS: The total number of paired US and digital VE assessments was 52, with a median of three per woman. Overall, 5% of sonopartogram parameters were not obtained compared with 18% of conventional digital VE parameters (P < 0.001). Assessment of cervical dilatation was possible in 86.5% of US examinations and 100% of digital VEs (P = 0.02), and dilatation was assessed as being greater by digital VE than by US (mean difference, 1.16 (95% limits of agreement, -0.76, 3.08) cm, r(2) = 0.68, P = 0.01). Fetal head descent was measured in all 52 cases by both methods (r(2) = 0.33, P < 0.001), but correlation between the two was only moderate. Head rotation was obtainable in 98% of US examinations and 46% of digital VEs (P < 0.001), with a mean difference of -3.9° (95% limits of agreement, -144.1°, 136.3°). CONCLUSION: In this proof-of-concept study, the acquisition of data regarding progress of labor was more successful for the sonopartogram than the conventional partogram. The agreement between digital VE and US was good for cervical dilatation and head rotation but less so for head descent. US assessment of the progress of labor is feasible in most cases.

A guide to the treatment of depression in women by estrogens.

Premenstrual depression, postnatal depression and climacteric depression are related to changes in ovarian hormone levels and can be effectively treated by hormones. It is unfortunate that psychiatrists have not accepted this form of treatment and this paper is an attempt to simplify this treatment, which should include transdermal estrogens, possibly testosterone and, if the woman has a uterus, also progestogen. A balance is often necessary between these three hormones. Transdermal estrogens in the appropriate dose will suppress ovulation and suppress the cyclical hormonal changes that produce premenstrual depression. Estrogens also have a mood-enhancing effect in postnatal depression and the depression in the transitional phase of the menopause. It is possible to add transdermal testosterone which will improve mood, energy and libido. The problem is the progestogen as these women are often progestogen-intolerant. Progestogen should be used in the lowest dose and for the shortest duration necessary to prevent endometrial hyperplasia or the return of premenstrual syndrome-type symptoms if the women are progestogen-intolerant. The use of estrogens for depression in these women does not exclude the use of antidepressants. Hormone-responsive depression cannot be diagnosed by measuring hormone levels but can only be diagnosed by a careful history relating depression to the menstrual cycle, pregnancies and the perimenopausal years. These appropriate questions should prevent the endocrine condition of premenstrual depression being misdiagnosed as bipolar disorder and the woman given inappropriate treatment.

'PROFOX'--the post HRT nightmare.

The recent report of a two-fold increase in esophageal cancer in women taking oral bisphosphonates is yet another reason to question current relegation of hormone replacement therapy (HRT) to a minor role in the correction of many problems occurring in the younger postmenopausal woman. Women under the age of 60 years with low bone density, flushes, sweats, vaginal dryness, loss of libido and climacteric depression would be treated with estrogens by gynecologists and most general practitioners. It is regrettable that bone physicians use bisphosphonates as first-line therapy in this age group, in spite of the growing number of serious complications reported. Similarly, psychiatrists have little experience in the use of estrogens for the reproductive depression syndrome of postnatal depression, premenstrual depression and perimenopausal depression, but use antidepressants. The adverse effects reported in the 2002 Women's Health Initiative study are given as justification for not using estrogens, although serious complications did not occur in women starting HRT before the age of 60 years. But, in reality, the objection to estrogens from psychiatrists and bone physicians preceded this study by decades and was a result of their unfamiliarity with this treatment. Regrettably, PROFOX (PROzac + FOsomaX) will become an established treatment for women who really need estrogens.

Therapeutic options for postmenopausal female sexual dysfunction.

BACKGROUND: Female sexual dysfunction (FSD) is a multidimensional problem combining biological, psychological and interpersonal elements of multiple etiologies. Menopause-related sexual dysfunction may not be reversible without therapy. Hormonal deficiency does not usually decrease in severity over time. Many options are available for the successful treatment of postmenopausal FSD. OBJECTIVE: To review the pharmacological and non-pharmacological therapies available for postmenopausal FSD, focusing on practical recommendations for managing postmenopausal women with sexual complaints, through a literature review of the most relevant publications in this field. PSYCHOSOCIAL THERAPY: This type of therapy (basic counselling, physiotherapy and psychosexual intervention) is considered an adaptable step-by-step approach for diagnostic and therapeutic strategies, normally combined with biomedical interventions to provide optimal outcomes. PHARMACOLOGICAL THERAPY: For postmenopausal FSD, many interventional options are now available, including hormonal therapies such as estrogens, testosterone, combined estrogen/testosterone, tibolone and dehydroepiandrosterone. CONCLUSIONS: Menopause and its transition represent significant risk factors for the development of sexual dysfunction. FSD impacts greatly on a patient's quality of life. Consequently, it is receiving more attention thanks to the development of effective treatments. Non-pharmacological approaches should be used first, focusing on lifestyle and psychosexual therapy. If required, proven effective hormonal and non-hormonal therapeutic options are available.

Estrogens as first-choice therapy for osteoporosis prevention and treatment in women under 60.

A case is made for estrogens to be the first-choice therapy for the prevention and treatment of osteoporosis in women below the age of 60 years. Estrogens produce a dose-related increase in bone density and also, by their effect on collagen, have a beneficial effect not only on the bone matrix but the intravertebral disc. Bisphosphonates do not have that effect upon the disc. Estrogens are also associated with other beneficial effects upon mood, vasomotor symptoms, pelvic atrophy, sexuality and quality of life. The data from the Women's Health Initiative (WHI) study are used as a justification for not using estrogens but the neglect of estrogen therapy by physicians antedated this and other studies by many years. Subsequent publications from the WHI study show that hormone replacement therapy, particularly estrogens alone, is not associated with the excess side-effects found in the older population. The substantial but non-significant decrease in heart attacks, breast cancer and mortality in women under the age of 60 taking estrogens alone should persuade the advisory bodies to revise their judgment on the benefits and safety of hormone replacement therapy in this population.

A study of women on long-term hormone replacement therapy and their attitude to suggested cessation.

OBJECTIVE: The study was undertaken to determine the effect of advice to discontinue hormone replacement therapy (HRT) on 100 women who were well established on treatment without side-effects. METHOD: The study was retrospective from November 2003 to April 2004, in a single gynecological practice in London, UK. One hundred consecutive long-term estrogen and testosterone hormone implant users were assessed as to their knowledge of recent studies regarding risks of long-term HRT and whether they wished to discontinue hormones. RESULTS: All women receiving estrogen and testosterone implants, for a mean duration of 17.65 years (range 10-28 years), felt well informed concerning the Women's Health Initiative Study and the Million Women Study but only three women were happy to discontinue. The reasons given for the continuation of therapy were that they felt well and their quality of life had greatly improved. The mean estradiol and testosterone levels were 921 pmol/l and 1.91 nmol/l, respectively. CONCLUSIONS: The high rate of continuation of hormone treatment indicates that, despite the recent adverse publicity, these women feel well informed and were not willing to discontinue with their hormone therapy if they felt well. A regular discussion of the risks and benefits of HRT remains mandatory.

Does retention of the ovaries improve long-term survival after hysterectomy? Prophylactic oophorectomy.

The controversy surrounding prophylactic oophorectomy is discussed. The importance of adequate hormone replacement with estradiol and particularly testosterone is discussed as is the severe limitation of considering publications which describe the unacceptable practice of hysterectomy and bilateral salpingo-oophorectomy without hormone replacement therapy. There remains a good argument for removal of ovaries at hysterectomy in women over the age of 40 with full discussion, consent and appropriate hormone replacement.

Hysterectomy and bilateral oophorectomy for severe premenstrual syndrome.

BACKGROUND: Premenstrual syndrome (PMS) is a chronic, poorly understood psycho-endocrine disorder severely affecting 5%; of women. Hormonal therapy which suppresses ovulation is the mainstay of medical treatment, but these interventions are rarely permanent. We evaluated the effectiveness and patient satisfaction with total abdominal hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO) in PMS sufferers, and assessed the post-operative HRT continuation. METHODS: All women undergoing TAH/BSO for severe PMS between January 1994 and April 2000 were interviewed and responses recorded by structured questionnaire. RESULTS: Forty-seven women were interviewed. Median age was 42 years (interquartile range 39.8-46.6) at the time of surgery. They had suffered with PMS for a mean of 9.68 years (SD 6.8) and received treatment for a mean of 3.57 years (SD 2.0) prior to referral to a gynaecologist. Fifty-two percent were treated with estradiol patches and 48% with estradiol implants prior to TAH/BSO. Ninety-six percent of women were 'satisfied' or 'very satisfied' with TAH/BSO, and 93.6% declared complete resolution of their cyclical symptoms; 93.6% were continuing with HRT usually by implants of estradiol and testosterone for a mean duration of 3.8 years (SD 1.86) post-operatively. CONCLUSION: Despite few reports of TAH/BSO as a treatment for severe PMS, we have found surgery, coupled with appropriate HRT, to be an extremely effective and well-accepted permanent cure for PMS.

Hormones and depression in women.

The biological plausibility for the effect of sex hormones on the central nervous system is now supported by a considerable amount of clinical data. This critical review guides the reader through the plethora of data, from the earliest reports of menstrual madness in the nineteenth century to neurobiological work in the new millennium. It illustrates through the scientific evidence base that, although the effect of estrogen on the central nervous system, particularly on mood and depression, remains a controversial area, there is now considerable evidence for the psychotherapeutic benefits of estrogens in the triad of hormone-responsive depressive disorders: postnatal depression, premenstrual depression and perimenopausal depression. The article also reviews the compelling data that testosterone supplementation has positive effects for depression, libido and energy, particularly where patients have only partially responded to estrogen therapy.

Premenstrual syndrome and the use of alternative therapies.

Premenstrual syndrome is a collection of symptoms that may be encountered by up to 95% of the population, although it is estimated to affect 5% of women severely. The use of complementary and alternative therapies is high among this group, but does not seem to compromise conventional treatment. It has been established that complementary therapies are used by a large proportion of the developed world, but their efficacy and safety are not always proven. This is partly due to the difficulty of studying alternative practices and the cost, but also with respect to premenstrual syndrome, problems with defining the condition and specifying end points are encountered. The difficulties in evaluating unorthodox therapies are elucidated and the evidence base for nonprescribed treatments for premenstrual syndrome is presented. Overall these women are a neglected group for whom the evidence for conventional therapy is sparse and controversial. Since the majority of women self-diagnose and self-medicate, it is important that physicians have an understanding of the variety of interventions tried and their worth.

Continuation of hormone replacement therapy after hysterectomy.

OBJECTIVES: To assess long-term hormone replacement therapy (HRT) usage in women after hysterectomy and to assess the relationship between age and long-term use of HRT in these women. Problems and comments of those women responding to a questionnaire were evaluated. MATERIAL AND METHODS: A postal semistructured questionnaire survey was performed in a single gynecological practice. A total of 545 consecutive women who had undergone a hysterectomy for benign conditions between January 1986 and September 1997 were studied, the main outcome measure being continuing use of HRT. RESULTS: There was a response rate of 83.1% to the questionnaire; 83% of all responders were taking HRT at the time of the survey. A continuation rate of 95.7% was found among women who had had a hysterectomy after 1994, and of 84.7% among those operated on in 1989 or before. Implants were used by 68%, transdermal patches by 17%, oral preparations by 11% and estradiol gel by 4%. Ten per cent of those not taking HRT at present indicated that they were likely to start again in the near future. No correlation was found between age and likelihood of HRT continuation. Fifty per cent of women responding to the questionnaire made further comments: 17.6% of these made specific positive comments regarding HRT, 16.7% reported weight gain, 9.7% suffered breast symptoms and 13.2% admitted concerns regarding breast cancer. CONCLUSIONS: A high HRT continuation rate of between 95.7% (women having had their hysterectomy less than 5 years ago) and 84.7% (women 10 or more years from their operation) can be achieved in the long term. Considering the high proportion having implant therapy, the use of testosterone as well as estradiol replacement may be a major factor in the greater adherence to HRT of this group.

Use of complementary therapies by women attending a specialist premenstrual syndrome clinic.

In this study, we investigate the use of complementary therapies by women attending a specialist premenstrual syndrome (PMS) clinic in the UK. Data was collected via an anonymous questionnaire survey of 100 women attending the clinic. Results showed 91% of women had used at least one form of complementary therapy for the management of their premenstrual symptomatology although only 35% were current users. Over half (53%) felt that these therapies had been of some benefit. Prescribed medication for PMS was being used by 71% of women at the time of the questionnaire and 83% of these women were satisfied with the perceived success of conventional therapy. In conclusion, the vast majority of women attending a specialist PMS clinic in the UK have used complementary therapies to treat this chronic debilitating condition but few continue use long-term. Treatment may be instigated by the woman with advice from her informal support network and/or her physicians. However as use is so prevalent, but with few randomized controlled trials conducted to show their benefits or risks, it is important to improve awareness of these therapies, both in qualitative and quantitative terms. Satisfaction with prescribed medications did not appear to be influenced by complementary therapy use in this group of women.

Five-year changes in bone density, and their relationship to plasma estradiol and pretreatment bone density, in an older population of postmenopausal women using long-term estradiol implants.

The aim of this study was to observe whether bone mineral density (BMD) improves over 5 years in older women using estradiol implants. A total of 18 women were selected who had commenced hormone replacement therapy (HRT) around the age of 60 years. The median age was 60.9 years (range 59.7-63.2 years). Each woman had a pretreatment bone scan and then received 6-monthly subcutaneous 50 mg estradiol implants. Twelve untreated women were also selected who had had bone scans at baseline and after 5 years. A comparison of the changes in BMD between treated and untreated women was made using the Wilcoxon rank-sum test. All changes at the hip and spine were statistically significant improvements from baseline in the estradiol-treated group. After 5 years of treatment, the estradiol-treated group had significantly improved bone mineral densities compared with the untreated group. At the spine, the plasma estradiol concentration is statistically significantly correlated with the 5-year increase in bone density (r = 0.717, p = 0.004). There was found to be an inverse relationship between the percentage increase in BMD over the 5-year period and initial bone density (r = -0.635, p < 0.005). Thus estrogen is seen to have the effect of improving bone density in older women over 5 years of treatment. The increase in vertebral bone density is most marked in those women with the highest plasma estradiol levels and the lowest pretreatment bone density.

Low dose 25 mg oestradiol implants and 1 mg norethisterone as continuous combined hormone therapy: a prospective study.

The anxiety regarding no-bleed regimens is that breakthrough bleeding and endometrial hyperplasia may occur. We aimed to demonstrate that 25 mg oestradiol implants can be adequately opposed by a low dose of progestogen protecting against osteoporosis. Twenty-two patients were recruited to the study. The mean age was 62 years and body mass index of 26.5. Median oestradiol rose from 77 pmol/L at baseline to 275 pmol/L at one year. Median endometrial thickness remained unchanged at 4 mm and only two women withdrew with bleeding problems. There was one case of proliferative endometrium at one year--all others samples were either atrophic or secretory. Lumbar bone density (L2-L4) rose significantly from 0.939 to 0.992 g/cm2 (6%, P = 0.005) and the total femoral density rose from 0.872 to 0.890 g/cm2 (+2.1%). Bone formation markers increased significantly (serum type 1 procollagen C terminal peptide, P1CP = 112-114, P = 0.0376) and bone resorption fell (serum type 1 collagen C terminal telopeptide, 1CTP = 3.0-2.9, P = 0.2863). E25 implants and low dose progestogen appear to avoid endometrial hyperplasia and bleeding problems while increasing bone density.

Hormone replacement therapy and malignant melanoma: to prescribe or not to prescribe?

The mean age of presentation of malignant melanoma in women is the early fifties, a time that may be concomitant with the onset of the menopause. As the lesion can often be successfully surgically excised, many women will enter the menopause disease-free but in need of treatment for their menopausal symptoms. Melanoma has traditionally been considered to be an estrogen receptor-positive tumor, whose prognosis is adversely affected by estrogen, whether during pregnancy or in association with the oral contraceptive pill or hormone replacement therapy (HRT). Recent evidence now refutes this. As most recurrences occur in the first 2 years following treatment, it may be prudent to defer HRT until this time. There is a particular paucity of information pertaining to HRT and melanoma, such that, at present, there appears to be no justification for withholding this potentially beneficial therapy from menopausal women who have undergone treatment for melanoma.

Prevalence of and satisfaction with complementary therapies and hormone replacement therapy in a specialist menopause clinic.

OBJECTIVE: To assess the usage of both conventional and complementary therapies by peri- and postmenopausal women for the treatment of menopausal symptoms. METHOD: A prospective questionnaire was completed by 200 consecutive patients attending a tertiary referral London-based specialist menopause clinic between September and December 1999. RESULTS: The median age of responders was 53.5 years (interquartile range 49-59). In total 137 women (68.5%) had ever tried an alternative treatment for the relief of their menopausal symptoms. Of these women 66% were regular users and 62% were satisfied with the effects of treatment. Women younger than the median age were significantly more likely to have used complementary therapies than older women (p = 0.036). Of the 200 participants, 184 women (92%) were current users of conventional hormone replacement therapy (HRT), and 89% were satisfied with the effects that their current HRT regimen had on their menopausal symptoms. Age was not related to satisfaction with conventional or complementary medicines. General practitioners and hospital doctors accounted only for 17% and 9%, respectively, of the primary sources of information for complementary medicines. CONCLUSIONS: High rates of usage and satisfaction were found with both conventional and complementary treatments for the relief of menopausal symptoms in our unit. For many of the women, both types of medicine are taken concurrently. Both general practitioners and hospital doctors are poor primary sources of information on complementary therapies for menopausal women.

Reduced bone mineral density in HIV-positive individuals.

A total of 105 HIV-positive patients underwent dual-energy X-ray absorbtiometry (DEXA) scan to assess bone mineral density (BMD). The prevalence of reduced BMD was found to be 71% and was higher in patients who had ever been treated with protease inhibitors (PI). Our results suggest a possible association between PI and reduced BMD, and further complicate the debate regarding when to commence treatment of HIV and with what agents to start.

Anabolic effect of long-term estrogen replacement on bone collagen in elderly postmenopausal women with osteoporosis.

Estrogen has been shown to stimulate osteoblasts in cell culture and increase bone formation in animal models. Such an anabolic effect of estrogen replacement therapy (ERT) would be beneficial to postmenopausal women with osteoporosis. Hence, we assessed the total collagen content and collagen crosslink maturity in iliac crest bone biopsy from 18 such women before and after 6 years of higher-dose ERT. These results were compared with the serum estradiol level and bone mineral density (BMD). Total collagen content of both cortical and cancellous bone increased, showing a median (95% CI) percent change of 6.7 (0.3-14.2) and 25.6 (13.5-33.8), respectively. Increase in collagen synthesis was supported by a rise in intermediate crosslinks in both cortical and cancellous bone, and mature crosslinks in cortical bone only. At the same time, BMD showed a substantial rise both at the lumbar spine and proximal femur with a median (95% CI) percent change of 28.6 (19.8-37.3) and 14.5 (8.4-20.7), respectively. Serum estradiol and BMD results correlated with cortical bone collagen levels. Our results suggest that long-term higher-dose ERT has a therapeutic role due to its anabolic effect on bone in postmenopausal women with osteoporosis.