Custom-compounded bioidentical hormone therapy: why so popular despite potential harm? The case against routine use.

Wide rejection of conventional hormone therapy (HT) after the initial publication of the Women's Health Initiative (WHI) led to unjustified use of custom-compounded bioidentical hormones. In the USA, it became an unregulated drug manufacturer industry in disguise, without proper control and making false claims and misleading advertisements. Manufacturing quality is not ensured. Unspecific harm from compounding has occurred on a large scale, such as deaths from infected products and end-stage renal failure plus carcinoma due to confusion between different Chinese herbs. Oral estrogens increase venous thromboembolic and ischemic stroke events, even more when overdosed; these excess risks can be avoided by non-oral administration, readily accessible in custom-compounded HT by administering estradiol through diverse routes (of which transdermal is the best documented). Another risk specific to custom-compounded HT, resulting from estrogen/progestogen imbalance, might be excess endometrial carcinomas. HT can be optimized by continuously combining transdermal estradiol with progesterone (when required). Registered preparations do exist for such a more physiological treatment and therefore must be preferred. Custom compounding is only seldom legitimate, for example in case of allergy (such as to peanut oil) or to prescribe different combinations, doses or components (e.g. estriol, dehydroepiandrosterone or testosterone), even when not approved by local regulatory authorities despite being scientifically acceptable.

Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol ± progesterone) are optimal.

The many advantages of registered bioidentical sex hormones over registered, conventional, non-bioidentical menopausal hormone therapy (MHT) are considered. The transdermal route of estrogen administration avoids excess venous thromboembolic and ischemic stroke events. There is some indication that conjugated equine estrogens are more thrombogenic and most likely induce some hypertensive responses; estradiol might also be superior to conjugated equine estrogens (CEE) in terms of global cardiovascular health. The most valid evidence presently suggests that CEE-only treatment does not increase the risk of breast cancer and even may reduce it. But its combination with a synthetic progestogen (mainly medroxyprogesterone acetate) is a critical issue since it seems to be primarily associated with an increased incidence of breast cancer, however similar to or lower than that associated with some common lifestyle factors. Though not yet proven in a randomized, controlled trial, MHT continuously combining oral micronized progesterone with transdermal estradiol can presently be considered as the optimal MHT. It is not only safer than custom-compounded bioidentical hormones but also than oral conventional MHT and has the best breast profile; registered products for such optimal MHT are available around the world and must be preferred.

Abstracts of the 24th international isotope society (UK group) symposium: synthesis and applications of labelled compounds 2015.

The 24th annual symposium of the International Isotope Society's United Kingdom Group took place at the Møller Centre, Churchill College, Cambridge, UK on Friday 6th November 2015. The meeting was attended by 77 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were welcomed by Dr Ken Lawrie (GlaxoSmithKline, UK, chair of the IIS UK group). The subsequent scientific programme consisted of oral presentations, short 'flash' presentations in association with particular posters and poster presentations. The scientific areas covered included isotopic synthesis, regulatory issues, applications of labelled compounds in imaging, isotopic separation and novel chemistry with potential implications for isotopic synthesis. Both short-lived and long-lived isotopes were represented, as were stable isotopes. The symposium was divided into a morning session chaired by Dr Rebekka Hueting (University of Oxford, UK) and afternoon sessions chaired by Dr Sofia Pascu (University of Bath, UK) and by Dr Alan Dowling (Syngenta, UK). The UK meeting concluded with remarks from Dr Ken Lawrie (GlaxoSmithKline, UK).

HRT optimization, using transdermal estradiol plus micronized progesterone, a safer HRT.

Hormone replacement therapy (HRT) remains the gold standard for treatment of climacteric symptoms in menopausal women; it is relatively safe in healthy subjects for at least 5 years, provided it had been initiated before the age of 60 years and/or within 10 years from menopause. Estrogen probably adds some cardioprotection, that can, however, be obscured by progestogens, especially medroxyprogesterone acetate (MPA). Oral HRT is associated with an increased risk of venous thromboembolism (VTE), gallbladder disease and possibly stroke. The increased occurrence of all these events can be prevented by the use of the transdermal route of estradiol administration; this route seems also advantageous for women with diabetes, hypertension and other cardiovascular risk factors, and also especially with advancing age. Endometrial protection by any progestogen is insufficient in the mid to long term when cyclical, sequential regimens are used; full protection can be secured only by continuous combined estrogen + progestogen. Natural, 'body-identical' progesterone, devoid of any androgenic as well as glucocorticoid activities but being slightly hypotensive due to its antimineralocorticoid activity, appears to be the optimal progestogen in terms of cardiovascular effects, blood pressure, VTE, probably stroke and even breast cancer (contrary to synthetic progestogens and particularly MPA, which appear to be mitogenic on breast cells, in synergism with estrogen). HRT optimization can thus be achieved by combining low doses of estrogen given transdermally with micronized oral progesterone; such optimized HRT will allow us to treat symptomatic women for as long as required. Asymptomatic women at risk of (osteoporotic) fractures can also be treated with this optimized HRT as long as their individual risk/benefit ratio remains favorable (thanks to the absence of increased risks of VTE, stroke and breast cancer).

Growth of long and aligned multi-walled carbon nanotubes on carbon and metal substrates.

Well aligned, long and dense multi-walled carbon nanotubes (CNT) can be grown on both carbon fibres and any metal substrates compatible with the CNT synthesis temperature. The injection-CVD process developed involves two stages, including fibre pretreatment by depositing a SiO(2)-based sub-layer from an organometallic precursor followed by CNT growth from toluene/ferrocene precursor mixture. Carbon substrates, as well as metals, can easily be treated with this process, which takes place in the same reactor and does not need any handling in between the two stages. The aligned CNT carpets obtained are similar to the ones grown on reference quartz substrates. The CNT growth rate is fairly high (ca. 30 µm min(-1)) and it is possible to control CNT length by varying the CNT synthesis duration. The thickness of the SiO(2)-based sub-layer can be varied and is shown to have an influence on the CNT growth. This layer is assumed to play a diffusion barrier layer role between the substrate and the iron based catalyst nanoparticles producing CNT. The CNT anchorage to the carbon fibres has been checked and good overall adhesion proved, which is in favour of a good transfer of electrical charge and heat between the nanotubes and fibre.

Optimized network of multi-walled carbon nanotubes for chemical sensing.

This work reports the design of a resistive gas sensor based on 2D mats of multi-walled carbon nanotubes (MWCNTs) grown by aerosol-assisted chemical vapour deposition. The sensor sensitivity was optimized using chlorine as analyte by tuning both CNT network morphology and CNT electronic properties. Optimized devices, operating at room temperature, have been calibrated over a large range of concentration and are shown to be sensitive down to 27 ppb of chlorine. The as-grown MWCNT response is compared with responses of 2000 °C annealed CNTs, as well as of nitrogen-doped CNTs and CNTs functionalized with polyethyleneimine (PEI). Under chlorine exposure, the resistance decrease of as-grown and annealed CNTs is attributed to charge transfer from chlorine to CNTs and demonstrates their p-type semiconductor behaviour. XPS analysis of CNTs exposed to chlorine shows the presence of chloride species that confirms electron charge transfer from chlorine to CNTs. By contrast, the resistance of nitrogen-doped and PEI functionalized CNTs exposed to chlorine increases, in agreement with their n-type semiconductor nature. The best response is obtained using annealed CNTs and is attributed to their higher degree of crystallinity.

[Asphyxiating thoracic dysplasia (Jeune syndrome): about two cases]. / Dysplasie thoracique asphyxiante ou syndrome de Jeune: à propos de deux cas.

Asphyxiating thoracic dysplasia (Jeune syndrome) is an osteochondrodysplasia with autosomal recessive inheritance, characterised by a nanism with rhizomelic predominance, associated with a narrow thorax. It induces an alteration of the respiratory function that conditions the prognosis, which is worsened in case of associated visceral lesions (probably related to mutations of genes implicated in ciliary development, as recently described). We report the observation of two severe cases of Jeune syndrome to emphasize the advancement of imaging, especially echography, and molecular biology in establishing prenatal diagnosis as well as prognosis of this syndrome.

Small cell carcinoma of the ovary successfully treated with radiotherapy only after surgery: case report.

UNLABELLED: Small cell ovarian tumors are rare and highly malignant, occurring mainly in young patients. Early mortality is high due to the lack of an effective treatment. The first adjuvant therapy is usually chemotherapy. CASE: During laparotomy for renal transplant in a 17-year-old girl, the right ovary exhibited a suspicious mass, whose pathological diagnosis was Stage 1A small cell ovarian tumor. Prognosis was poor (young age, hypercalcemia, tumor >10 cm, and presence of large cells). Since chemotherapy is contraindicated for dialysed patients, only radiotherapy was given. The patient is still alive and disease-free ten years after diagnosis. CONCLUSION: This is the first case with a poor prognosis reported in the literature that has been successfully cured by surgery plus adjuvant radiotherapy only.

In vitro investigation of oxide nanoparticle and carbon nanotube toxicity and intracellular accumulation in A549 human pneumocytes.

If released in the environment, nanomaterials might be inhaled by populations and cause damage to the deepest regions of the respiratory tract, i.e., the alveolar compartment. To model this situation, we studied the response of A549 human pneumocytes after exposure to aluminium oxide or titanium oxide nanoparticles, and to multi-walled carbon nanotubes. The influence of size, crystalline structure and chemical composition was investigated. After a detailed identification of nanomaterial physico-chemical characteristics, cells were exposed in vitro and viability and intracellular accumulation were assessed. In our conditions, carbon nanotubes were more toxic than metal oxide nanoparticles. Our results confirmed that both nanotubes and nanoparticles are able to rapidly enter into cells, and distribute in the cytoplasm and intracellular vesicles. Among nanoparticles, we demonstrate significant difference in biological response as a function of size, crystalline phase and chemical composition. Their toxicity was globally lower than nanotubes toxicity. Among nanotubes, the length did not influence cytotoxicity, neither the presence of metal catalyst impurities.

Dispersion study of long and aligned multi-walled carbon nanotubes in water.

Dispersion of nanotubes is a crucial step for many applications. The properties of the final nanotube-based material are strongly dependent on the quality of nanotube suspensions. In this study, long and aligned multi-walled carbon nanotubes obtained by catalytic chemical vapour deposition were dispersed in water with different dispersing agents using high intensity ultrasounds. Among different additives, we selected sodium dodecyl sulfate (SDS) as dispersing agent to prepare suspensions of nanotubes. UV-Visible spectrometry method was used to measure the influence of dispersion parameters (power and duration of sonication) on dispersion state and suspension stability. Therefore, we demonstrated that, even if high intensity ultra-sounds are breaking nanotubes, it is possible to obtain stable water-based suspensions containing MWNTs which exhibit length up to 20 microm.

The long-term tolerability and efficacy of OESCLIM: results of a 1-year study.

OBJECTIVES: A 1-year, open-label, non-comparative study evaluated the long-term tolerability and acceptability of a new generation matrix patch in post menopausal women with estrogen deficiency. METHODS: Menopausal women (224) from 37 centres in five European countries received OESCLIM 50 microg/d (17-beta estradiol) for 3 months, titrated if necessary to either 25 or 100 microg/d for a further 9 months. Patients received either a continuous or discontinuous estradiol regimen with concomitant sequential progestogen (except hysterectomised patients). Skin tolerability was assessed by patient diaries and questionnaires. Global tolerability, efficacy, laboratory parameters and global acceptability were also monitored. RESULTS: Almost two-thirds of women did not experience any kind of skin reaction and only 4.3% of all applications (752/17,702) caused site reactions. Of these, the majority caused only slight or no discomfort (63.2%). Only 0.37% of total applications required patch removal; none required therapy. A low percentage of patients withdrew due to tolerability issues: 2.7% due to skin reactions; 7.5% due to hyperestrogenism. The mean number of hot flushes experienced by symptomatic women reduced by 91% from 4.0 at baseline to 0.4 after 2 months. Total cholesterol reduced by 3.9% and LDL cholesterol by 5.1%, with no increase in triglyceride levels. Investigators assessed treatment as effective in 96.8% of cases; well tolerated locally in 93.1% and well tolerated generally in 89.5%. At the end of this 1 year study, 79% of patients wished to continue therapy. CONCLUSION: OESCLIM is well tolerated locally and systemically in long-term therapy with a high proportion of patients wishing to continue therapy after 1 year.

The efficacy and tolerability of long-term cabergoline therapy in hyperprolactinaemic disorders: an open, uncontrolled, multicentre study. European Multicentre Cabergoline Study Group.

OBJECTIVE: We assessed the efficacy and safety of the new, long-acting dopamine agonist drug cabergoline during long-term therapy of hyperprolactinaemia. DESIGN: Open, prospective, multicentre study. PATIENTS: One hundred and sixty-two females with either a microprolactinoma (n = 100), idiopathic hyperprolactinaemia (n = 54), empty sella syndrome (n = 7) or residual hyperprolactinaemia after surgery for a macroprolactinoma (n = 1). All had previously been treated with cabergoline or placebo for 4 weeks as part of a dose-finding study. MEASUREMENTS: Menstrual pattern, adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function were assessed after one month and subsequently at two-monthly intervals. RESULTS: Treatment was started at doses of 0.25 mg (n = 3), 0.5 mg (n = 8), 1 mg (n = 150) or 2 mg (n = 1) per week, given either as a single weekly dose (n = 8) or divided into twice-weekly doses (n = 154), and was continued for at least 49 weeks in 123 patients. Final treatment doses ranged from 0.25 mg fortnightly to 2 mg twice weekly: most patients finished the study taking 0.5 mg once (n = 31) or twice (n = 77) weekly. Stable normalization of PRL levels was achieved in 138 subjects (85%), in 129 of whom the effective dose was < 1 mg per week. In the subset of 114 patients completing 49 weeks of therapy and having dose adjustments according to the protocol, the biochemical success rate was 92%. Fifty-nine of the 65 previously amenorrhoeic women (91%) and 44 of the 49 (90%) who were previously oligomenorrhoeic resumed regular menses and/or became pregnant during the study. Adverse events were reported in 64 patients (39.5%). In 84% of cases with adverse events, the symptoms were of mild or moderate severity and most occurred during the first few weeks of therapy; five patients (3%) discontinued treatment because of poor tolerance. The most frequent symptoms were dizziness (13% of patients), headache (13%), nausea (10%) and weakness and/or fatigue (10%). Of 27 patients who had previously been poorly tolerant of other dopamine agonists, 17 (63%) did not experience any side-effects and only one was intolerant of cabergoline. No adverse haematological or biochemical effects were detected except for a slight downward trend in haemoglobin which may have been related to the resumption of regular menses in previously amenorrhoeic or oligomenorrhoeic women. A mild hypotensive effect was observed, mean systolic and diastolic blood pressures falling by 5 and 4 mmHg respectively during treatment. CONCLUSIONS: The results provide evidence for the long-term effectiveness and safety of cabergoline in the treatment of hyperprolactinaemia. Its ability to normalize PRL and restore gonadal function compares favourably with reported data on reference compounds while its tolerability profile and simple administration schedule offer potential advantages in terms of patient acceptability.

Dose-dependent suppression of serum prolactin by cabergoline in hyperprolactinaemia: a placebo controlled, double blind, multicentre study. European Multicentre Cabergoline Dose-finding Study Group.

OBJECTIVE: Dopamine agonists have a well established place in the treatment of hyperprolactinaemic disorders but their use is associated with a high incidence of adverse effects. We have investigated the biochemical efficacy and side-effect profile of a range of doses of the novel, long-acting dopamine agonist, cabergoline, in suppressing prolactin (PRL) in hyperprolactinaemic women. DESIGN: Multicentre, prospective, randomized, placebo controlled and double blind. PATIENTS: One hundred and eighty-eight women with hyperprolactinaemia secondary to microprolactinoma (n = 113), idiopathic disease (n = 67), empty sella syndrome (n = 7) or following failed surgery for a macroprolactinoma (n = 1). MEASUREMENTS: Weekly assessment of adverse symptoms, blood pressure and pulse, serum PRL, blood count, liver and renal function. RESULTS: Patients received either placebo (n = 20) or cabergoline 0.125 (n = 43), 0.5 (n = 42), 0.75 (n = 42) or 1.0 mg (n = 41) twice weekly for 4 weeks. The five treatment groups were comparable in age (mean 31.8, range 16-46 years), diagnosis, previous therapy, and pretreatment serum PRL. PRL was suppressed to below half the pretreatment level in 5, 60, 90, 95 and 98% and normalized in 0, 30, 74, 74 and 95% of patients taking placebo or cabergoline 0.125, 0.5, 0.75 or 1.0 mg twice weekly respectively (Armitage's test, chi 2 = 39.3, P < 0.01). Cabergoline therapy (all doses) restored menses in 82% of the amenorrhoeic women not previously treated with dopamine agonists. Adverse events were recorded in 45% of patients in the placebo group and in 44, 50, 50 and 58% of those taking 0.125, 0.5, 0.75 and 1.0 mg cabergoline twice weekly (Armitage's test, P > 0.05). Over 95% of reported symptoms were relatively trivial, most frequently transient nausea, headache, dizziness, fatigue and constipation. More severe adverse events, interfering significantly with the patients' lifestyle, occurred in 13 (7.7%) patients taking cabergoline; treatment withdrawal was necessary in only one case. No adverse effects were detected on blood pressure or haematological or biochemical parameters. CONCLUSIONS: We have shown a linear dose-response relationship for cabergoline in the treatment of hyperprolactinaemia in the range 0.125-1.0 mg twice weekly, with normalization of PRL in up to 95% of cases and acceptable tolerability throughout the dose range.

Sex hormones and cardiovascular risk.

PIP: The metabolic effects of sex steroids pertinent to cardiovascular risk are described. These effects are discussed for estrogen inducible proteins, coagulation and fibrinolysis, blood pressure and hypertension, carbohydrate metabolism, lipids and lipoproteins, and vessel walls and local prostaglandins. Also described is the cardioprotection from estrogens and estrogen/progesterone treatment and cardiovascular risk. Oral contraceptive (OC) and cardiovascular risk are also discussed with the following effects identified: the influence on many of the multiple risk factors involved in the development of cardiovascular diseases (i.e., lipids, carbohydrate metabolism, and hemostasis), an association between OC use and thromboembolic accidents, a state of hypercoagulability counterbalanced by increased fibrinolytic activity, venous thrombosis, a relationship with the dosage of androgenic progestogens. no atherogenic origin, no age limit for prescribed, healthy, nonsmoking women, and an increased peripheral insulin resistance. It is concluded that it is rarely inadvisable to prescribe low dose natural estrogens in postmenopausal hormone replacement therapy. Factors contraindicating such use are undiagnosed genital bleeding, an active thrombolic or cardiovascular process, carcinoma of the breast or endometrium, and acute liver failure. Estrogen replacement therapy may exert some cardioprotective effect. When progestogens are added to prevent endometrial carcinoma development, the benefits might be reduced. Low estrogen and low progesterone OC use among healthy, nonsmoking women even in middle age poses no risk of death from cardiovascular disease. Premenopausal women may even be protected from coronary atherosclerosis with estrogen-containing OCs. However, it is advisable that OCs be used with the least possible impact on lipid and carbohydrate metabolism, as well as on hemostasis. For those with some prior cardiovascular risk, there are theoretical advantages at present for use of the new, less, or nonandrogenic progestins in OCs; however, caution is urged and informed consent must be obtained until epidemiological studies support this position.^ieng

[Local growth factors for breast cancer: general review and potential value for clinician]. / Les facteurs de croissance locaux du cancer mammaire: revue générale et intérêt potentiel pour le clinicien.

The discovery of a panel of peptides produced by normal and cancerous cells and capable of stimulating cell growth in an autocrine and paracrine fashion has been witnessed in recent years. This article focusses on the local growth factors thought to play a role in the biology of breast cancer and reviews which growth factors' receptors have been associated with prognosis of primary breast cancer. The potential of those growth factors for the development of new anticancer treatment strategies is also briefly discussed.

Risks of estrogens and progestogens.

PIP: The risks and benefits of specific types of postmenopausal estrogens and progestogens are explored: those affecting serum lipids, clotting elements, hepatic proteins synthesis, blood pressure, glucose tolerance, endometrial, breast and cervical cancer. Ethinyl estradiol taken orally is the only estrogen likely to cause gall bladder disease. It also induces liver protein synthesis when taken orally or vaginally. Natural estrogens do not heighten coagulation factors, and may shift towards fibrinolysis. Both ethinyl estradiol and equine estrogens may increase blood pressure, while natural estrogens may decrease it. Similarly natural estrogens induce prostacyclin synthesis, while ethinyl estradiol activates both prostacyclin and thromboxanes. Progestagens, especially so the norprogestins, disturb carbohydrate metabolism and tend to reverse the beneficial effects of estrogens on serum lipids, a 40-70% reduction in risk of mortality from coronary heart disease. A meta- analysis of 23 studies concluded that menopausal estrogens do not increase the risk of breast cancer by a measurable degree, except in high doses and in those predisposed by family history. There is an increased risk of endometrial carcinoma for those taking unopposed estrogens for more than 3-6 years. This can be attenuated by taking combined estrogen-progestins, which will eventually result in absence of bleeding, or a 12-day progestogen course every 4-6 cycles. Oral micronized progesterone decreases blood pressure. The relative androgenic effects of progestins other than the norprogesterone derivatives are less significant. As an alternative to taking a progestogen, a woman could have regular endometrial sampling or abdominal or vaginal sonograms to detect endometrial cancer.^ieng

Effects of the short-acting benzodiazepine triazolam, taken at bedtime, on circadian and sleep-related hormonal profiles in normal men.

Studies in rodents have shown that triazolam, a commonly used hypnotic, may shift circadian rhythms, with the direction and magnitude of the phase-shifts being dependent on the time of drug administration. To determine whether benzodiazepine, taken at standard bedtime, modifies the amount and/or temporal organization of hormonal secretion, six normal men were studied during basal conditions and on the first and third days of treatment with 0.5 mg triazolam. In each study, sleep was polygraphically monitored and plasma cortisol, growth hormone (GH), melatonin, and prolactin (PRL) (i.e., hormones influenced by circadian rhythmicity and/or sleep) were measured at 20-min intervals for 24 h. The sleep latency and the number and duration of awakenings were reduced during triazolam treatment as compared to baseline conditions. The only alteration of sleep architecture was a partial suppression of stages III + IV (SW) in late sleep. Triazolam did not affect the mean cortisol and melatonin levels or the total amount of GH secreted over the 24-h span. The circadian timings of the onsets of cortisol and melatonin secretions were essentially unaltered. The nocturnal rise of melatonin was prolonged by 45 to 60 minutes. Sleep-associated GH release was not modified by triazolam. Sleep-associated PRL secretion persisted, but in half of the nights studied was enhanced almost threefold. This effect of the drug on nocturnal PRL secretion was not specific to either the first or the third night of treatment, nor was it specific to certain subjects. Irrespective of the magnitude of the nocturnal elevation, morning PRL levels were slightly but consistently higher after triazolam treatment than under basal conditions. Normal PRL levels resumed around noon. In conclusion, administration of 0.5 mg triazolam at normal bedtime (2230) for three consecutive days may induce a transient hyperprolactinemia, but does not abolish sleep-related hormone secretion and does not affect the timing of endocrine events controlled by the circadian clock. These findings are consistent with studies in hamsters where treatment with triazolam in the early subjective night was also without effect on the rodent circadian clock.

The 24-hour profile of plasma prolactin in men with major endogenous depressive illness.

Plasma prolactin (PRL) levels were measured at 15-minute intervals for 24 hours in 18 men suffering from major endogenous depressive illness and in 7 age-matched healthy men. Eleven of the 18 depressed patients were restudied during clinical remission following either electroconvulsive therapy or treatment with amitriptyline hydrochloride. During the acute phase of the illness, the unipolar depressed patients had fragmented patterns of PRL secretion with an early timing of the nocturnal secretory phase of PRL, which started, on the average, 2 hours earlier than in healthy subjects. Moreover, the amplitude of the circadian variation of PRL was reduced in these patients, with subnormal PRL levels occurring during the midsleep period. This latter abnormality was also observed in bipolar patients, who had otherwise normal PRL profiles. These lower midsleep PRL concentrations were associated with a significant increase in the amount of time spent awake during the same period. Antidepressant treatment did not consistently correct the abnormalities in the patterns of PRL release observed during the acute phase of the illness. These results indicate that early timing of nocturnal PRL secretion and damping of the nighttime PRL elevation may be found in men with endogenous depressive disorders. In contrast to disturbances of the corticotropic and somatotropic axes, these abnormalities of PRL secretion may still be present during clinical remission following antidepressant treatment.

From oral contraception to hormone replacement therapy: towards a continuum?

PIP: On the basis of available evidence, it is reasonable to conclude that at this time women between 35-45 years should not be denied the benefit of oral contraception (OC) if they do not smoke. As Upton recently reported, the risk of death due to pregnancy and childbirth, even in a developed country such as the US, is greater than the risk of OC, including the risk for OC users who smoke. Low-dose, or very low-dose, ethinyl-estradiol combined OCs most likely can be prescribed safely for most women up to the time of menopause in the absence of cardiovascular risk factors. The alternative treatments that might be initiated before and then continued during and after the climacteric include: cyclic or continuous combined estrogen-progestogen preparations containing estradiol (in valerate or micronized form); "transdermal therapeutic systems" delivering both estrogen and progestogen, for cyclic or even continuous use; and other newly-developed means of delivering fairly constant doses of steroids, such as pellet implants and microspheres. The combination of estradiol pellet implants with the cyclic or continuous administration of progesterone or a progestogen also might prove to be a promising approach if estrogen accumulation could be avoided. Substantial effort still needs to be made to improve the available preparations and provide the clinician and the women concerned with the best possible formulations for use in the perimenopause, and possibly indefinitely afterwards as true substitution therapy.^ieng