Hormone Replacement Therapy Products Research Articles

Hormone replacement therapy perspectives.

Hormone replacement therapy (HRT), also known as menopausal hormone therapy (MHT), was looked upon as a fountain of youth that kept women young and reduced cardiovascular disease. This led to a large-scale study called the Women's Health Initiative (WHI) that was conducted to show the cardiovascular benefits of HRT. This study was suspended early because of adverse side effects. The USFDA responded by slapping a "black box" warning on all HRT products. USFDA-approved bioidentical HRT formulations are safe and effective. We propose that these formulations have the "black box" warning removed so that doctors feel more confident in prescribing these products for symptoms of menopause and chronic conditions such as cardiovascular health. We propose eliminating the sale of products containing medroxyprogesterone acetate (MPA) because of the increased risk of heart attacks and breast cancers associated with this medication.

Simultaneous voltammetric determination of female hormones using different carbonaceous electrodes in a non-aqueous environment

An undemanding electroanalytical method for the simultaneous determination of estrogens, namely 17β-estradiol (E2) or synthetic 17α-ethinylestradiol (EE2), with dienogest (DGN) has been developed for the analysis of oral contraceptives and hormone replacement therapy products. This approach is based on their anodic oxidation at carbonaceous electrode materials in pure acetonitrile using square-wave voltammetry. The electrochemical behaviour of these hormones at a glassy carbon electrode (GCE) in a nonaqueous environment was investigated using cyclic voltammetry to verify their reaction mechanisms. As part of the optimisation, commercially available GCE and boron-doped diamond electrodes were found to provide similar analytical performance, characterized by a wide linear range (>100 μmolL−1) with limits of quantification approximately 1.6 μmolL−1 for each hormone. A satisfactory precision (relative standard deviation < 4%) has been achieved for a mixture of 10 μmolL−1 E2 and DGN. Finally, the developed electroanalytical method was applied to the determination of female hormones present in pharmaceutical preparations and the results acquired were comparable to those obtained by a reference method employing reversed-phase high-performance liquid chromatography coupled to a diode array detector, which confirmed the practical use of this method in routine pharmaceutical analysis.

Hormone replacement therapy pre-payment scheme is too 'complex', say pharmacy leaders

Women in England will be able to buy a new pre-payment certificate (PPC) for hormone replacement therapy (HRT) from 1 April 2023, the government has announced. The certificate, priced at £18.70 (the cost of two single prescription charges) will cover 43 HRT products and be valid for 12 months, but pharmacy leaders have warned that […]

Consensus-led recommendations supporting choice and personalisation of Hormone replacement therapy in menopause care.

Inequity of access and choice to different hormone replacement therapy (HRT) products across the UK has been suggested (Hillman, 2020). While, the cause is not entirely understood, potential contributors include conflicting national guidance, economic deprivation and a local formulary approach. With a diverse and growing population of women reaching and living well beyond the menopause, the impact of this inequity is becoming more pronounced, and challenges the goal of providing personalised care. The study objective is to establish a consensus that supports a greater equity of access and choice of HRT and provision of individualised care. Modified Delphi study designed by UK HCPs with expertise in menopause care. This group identified 40 consensus statements over four key topics, related to access and choice of different HRT products. An online 4-point Likert scale questionnaire, sent to UK HCPs, was used to assess agreement, with a consensus threshold set at 75%. 150 HCP responses between June and September 2021. A total of 137 responses were received. Analysis identified 37/40 statements attaining very high agreement (≥ 90%) and 3/40 statements attaining high agreement (< 90% and ≥75%). Nine recommendations were developed with the intent to inform potential improvements to menopause care in the UK. The high levels of agreement displayed suggest a desire to change the way menopause care is delivered in the UK. Implementation of the suggested recommendations has the potential to improve equity of access to licensed treatment options, compliant with the NICE recommendation for personalisation of care.

MHRA consults on making first HRT product available over the counter

The Medicines and Healthcare products Regulatory Agency (MHRA) has launched a consultation on making the first hormone replacement therapy (HRT) product available in pharmacies without a prescription. Gina (estradiol; Novo Nordisk) is a local oestrogen therapy, used primarily to treat vaginal atrophy caused by oestrogen deficiency in postmenopausal women. The condition can lead to symptoms […]

First HRT product in the UK to be made available without a prescription

For the first time, women in the UK will be able to access hormone replacement therapy (HRT) in community pharmacies without a prescription, the Medicines and Healthcare products Regulatory Agency (MHRA) has confirmed. Following a safety review and public consultation, in which over 88% of 1,229 respondents were in favour of the move, Gina 10 […]

Molecular Pathways: Estrogen Pathway in Colorectal Cancer

Worldwide, colorectal cancer has a higher incidence rate in men than in women, suggesting a protective role for sex hormones in the development of the disease. Preclinical data support a role for estrogen and its receptors in the initiation and progression of colorectal cancer and establishes that protective effects of estrogen are exerted through ERβ. Hormone replacement therapy (HRT) in postmenopausal women as well as consumption of soy reduces the incidence of colorectal cancer. In the Women's Health Initiative trial, use of HRT in postmenopausal women reduced the risk of colon cancer by 56% [95% confidence interval (CI), 0.38-0.81; P = 0.003]. A recent meta-analysis showed that in women, consumption of soy reduced the risk of colon cancer by 21% (95% CI, 0.03-0.35; P = 0.026). In this review, using the preclinical data, we translate the findings in the clinical trials and observational studies to define the role of estrogen in the prevention of colorectal cancer. We hypothesize that sometime during the tumorigenesis process ERβ expression in colonocytes is lost and the estrogen ligand, HRT, or soy products, exerts its effects through preventing this loss. Thus, in the adenoma-to-carcinoma continuum, timing of HRT is a significant determinant of the observed benefit from this intervention. We further argue that the protective effects of estrogen are limited to certain molecular subtypes. Successful development of estrogen modulators for prevention of colorectal cancer depends on identification of susceptible colorectal cancer population(s). Thus, research to better understand the estrogen pathway is fundamental for clinical delivery of these agents.

The Miracle Drugs: Hormone Replacement Therapy and Labor Market Behavior of Middle-Aged Women

Abstract: In an aging society, determining which factors contribute to the employment of older individuals is increasingly important. This paper sheds light on the impact of medical innovation in the form of Hormone Replacement Therapy (HRT) on employment of middle-aged women. HRT are drugs taken by middle-aged women to soften symptoms related to menopause. Before 2002, HRT products were among the most popular prescription drugs in America. We use the timing of the release of information of the potential hazardous effects of HRT—uncovered in 2002 by the largest randomized trials on women ever undertaken—as an instrument for the purchase of the affected drugs within a Fixed Effect Instrumental Variable framework. We find that HRT use impacts employment: namely, that HRT use increases employment by 25 percentage points among middle-aged women who would have taken HRT but who do not take HRT after the release of information of its potential hazardous effects.

Cambios en el uso de la terapia hormonal sustitutiva tras una intervención informativa dirigida a mujeres y prescriptores

Objective To describe changes in prescription of hormone replacement therapy (HRT) in Asturias (Spain) after the publication of the results of the Women's Health Initiative and the Million Women Study and following the recommendations of the Spanish Drugs Agency to women and prescribers (2004–2005). Methods We performed a quasiexperimental study with no control group. The data used consisted of sales of HRT products from 1996 to 2003 (preintervention period). In 2004 and 2005, annual sales of HRT products and the percentage of women using HRT among the population aged 50–59 years were analyzed. To analyze trends in costs, we used the price of each product in pesetas until 2001 and in euros thereafter. Results Sales of HRT increased until 2001. Total sales declined by 73.6% between 2001 and 2005. The decrease between 2004 and 2005 (49.1%) was twice that observed between 2002 and 2003 (24.5%). An estimated 17.2% of women aged 50–59 years old were using HRT in 1996 compared with 4.1% in 2005. The total pharmaceutical cost related to HRT showed a similar decrease, although sales of Boltin ® (tibolone) increased by two-fold. Conclusions Systematic and independent educational interventions aimed at women in the general population and prescribers are both effective and necessary. The HRT epidemic and its health costs, as well as the shift to tibolone prescription and the adverse effects of this drug, should be investigated nationwide.

Changes in utilisation of hormone replacement therapy in Australia following publication of the findings of the Women's Health Initiative

To examine the impact of publication of the findings of the Women's Health Initiative (WHI) on the utilisation of hormone replacement therapy (HRT) in Australia with particular reference to the influence that media may have had on prescriber and consumer behaviour. Retrospective data from the Australian Government Department of Health, Ageing DUSC Database and media hits from Factiva were reviewed to obtain prescription numbers, total cost and cost to the pharmaceutical benefits scheme and number of media hits from the year before publication of the combined HRT arm of the WHI. Prescribing of HRT products decreased significantly immediately following publication of the combined HRT arm of the WHI and continued to decline at a slower rate following publication of the memory and oestrogen only arms of the study. These results represent a more accurate national estimate of the change in HRT use in Australian women relative to previous findings from surveys carried out in Australia.

Hormone Replacement Therapy after Prophylactic Adnexectomy

In France, the National Collective Statement from the INSERM [1] recommends a prophylactic adnexectomy (PA) in women having an increased ovarian cancer risk due to mutations in BRCA1 or BRCA2 either at 40 years of age or at 35 years of age if the woman has decided she no longer wants children. PA can reduce the risks of ovarian cancer by more than 90% and breast cancer by more than 50%. However, the lack of oestrogen production caused by PA has numerous consequences. These are more pronounced in young women and include hot flushes, vaginal dryness, sexual troubles, joint stiffness and in the long term osteoporosis. Recent data from the large randomised American WHI Study [2,3] have led the medical community to re-evaluate the benefits and risks of hormone replacement therapy (HRT) and to modify their prescription practices. As data on the HRT products used in France are not available, French agencies have recommended that in the general population HRT should be used at the lowest dose and for the shortest duration possible, and then only for menopausal problems [4]. Currently, many women in France are reluctant to use HRT because of the results of these studies. Gynaecologists also are reluctant to prescribe HRT due to the risk of legal proceedings in cases of cancer. This reluctance is much greater for women with increased risk of breast cancer. Although the Markov Model for predisposed women shows a favourable benefit/risk ratio for short-term HRT prescription, this analysis was carried out without precise data for the effect of HRT on predisposed women [5]. Moreover, breast cancer in women undergoing HRT may be falsely attributed to HRT due to the high incidence of breast cancer associated with BRCA1/2 mutations. We have observed that PA is relatively well accepted in peri-menopausal women (for example after chemotherapy), although some young women still refuse or delay PA despite there being a high incidence of ovarian cancers in their family. At the Curie Institute, we take into account the preferences of women after they have been thoroughly informed: 1. We recommend PA to women at 40 years of age if they have a BRCA1 mutation, or a BRCA2 mutation and a family history of ovarian cancer, and at 50 years of age if they have a BRCA2 mutation without a family history of ovarian cancer. 2. In women unaffected by breast cancer, we give very complete information on the benefits and risks of HRT and alternatives, such as symptomatic treatments for hot flushes, vaginal oestrogens, and non-hormonal treatment for osteoporosis. 3. We always propose psychological support to allow each woman to estimate and anticipate the consequences of PA. 4. In case of uterine diseases such as fibroma, surgeons may propose a hysterectomy as well as PA, in which case oestrogens can be prescribed alone and progestins can be avoided (4). 5. After PA, a gynaecological consultation is offered: HRT is given only to thoroughly informed women who really want it and have accepted PA with the assurance that they would have HRT afterwards. HRT is also offered to women who have had a prophylactic bilateral mastectomy. For other cases, clinical follow-up is proposed, and osteodensitometry is prescribed. If menopausal problems occur, alternative treatments are proposed first. For persistent problems, HRT is prescribed at the lowest dose for as long as the woman wishes. It is strongly recommended that treatment be stopped at the natural age of menopause, around 50 years of age. We think that over-alarmist information on menopause and strongly held beliefs against HRT lead some young women to refuse or delay an intervention that may save their life. Therefore, we advocate clear information, honest dialogue, and shared decision making with each woman.

Hormone replacement therapy in Germany: Determinants and possible health-related outcomes: Results of National Health Surveys from 1984 to 1999

Objectives To explore the determinants of hormone replacement therapy (HRT) use and possible health-related outcomes in Germany. Methods 827 current HRT users (age range 31–78 years, who had taken HRT products in the last 7 days before the medical interview) and 2371 age-matched nonusers were identified from five population-representative National Health Surveys performed from 1984 to 1999 in Germany. Cross-sectional comparisons between HRT users and nonusers were performed for socioeconomic factors and possible health-related outcomes. Regression models were used to obtain odds ratios of HRT use. Results HRT use increased dramatically from 3% in 1984/1985 to 21% in 1998/1999 among German women aged 40–69. Regression analysis and comparison between HRT users and nonusers suggested that HRT use was closely associated with socioeconomic factors and personal lifestyle that may favor better health. In HRT users, however, we did not observe any health-related benefits in satisfaction with life or health. While HRT users appeared superior to nonusers with respect to the glycemic status, histories of cardiovascular diseases, despite a favorable lipid profile, occurred not less than in the group of nonusers. Conclusions In the settings of our cross-sectional studies in Germany HRT did not improve users’ health benefits and did not show cardioprotective effects. The better glycemic status should be balanced against the higher risks of cardiovascular diseases and breast cancer.

Tibolone and Endometrial Cancer

Case series and spontaneous reports of endometrial cancer have raised the question as to whether the use of tibolone (introduced into the UK in 1991) is associated with an increased risk of endometrial cancer. This study set out to evaluate whether tibolone use is associated with an increased risk of endometrial cancer. Age-adjusted incidence rate ratios (IRRs) of endometrial cancer were calculated for tibolone use compared with the use of other hormone replacement therapy (HRT). Separate sets of controls, matched for age and general practice, were compared with cases, all nested within a cohort of HRT users identified from the UK General Practice Research Database (GPRD). Conditional logistic regression analysis, adjusted for potential confounders, was used to study the association between tibolone use and the risk of endometrial cancer. 4995 women used tibolone as their first HRT product; 10 783 (4.3%) of the users of combined HRT had changed to tibolone at some time during the study period. Amongst women whose HRT began with tibolone, the age-adjusted IRR relative to those who started with combined sequential HRT was 1.83 (95% CI 1.19, 2.82). The nested case-control study comprised 162 cases, each matched to two sets of 972 controls. There were 43 tibolone-exposed subjects, 28 of whom had used other HRT before or after tibolone. The adjusted odds ratio of the risk of endometrial cancer in women who had ever used tibolone, compared with users of combined sequential HRT, was 1.54 (95% CI 1.03, 2.32) in the age-matched set and 1.58 (95% CI 1.01, 2.47) in the practice-matched set. Sensitivity analyses did not decrease the risk estimates found. Tibolone may be associated with an increased risk of endometrial cancer compared with conventional forms of HRT, but our data are fragile. Residual bias and uncontrolled confounding cannot be excluded, and follow-up time is insufficient to draw any firm conclusions with respect to the endometrial safety of tibolone.

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Availability of Hormone Replacement Therapy Products in Canada

To determine the availability in Canada of different types of hormone replacement therapy (HRT) products, and to compare the availability of HRT products in Canada to their availability in other countries. A systematic review was conducted of the availability of products indicated for treatment of menopausal symptoms in Canada, the United States (US), the United Kingdom (UK), Sweden, and Australia. Products indicated for the treatment of menopausal symptoms were determined for each country by using on-line drug product databases. Products administered by injection and androgen products, unless combined with estrogens, were excluded from the analysis. There were 111 different brands identified in the 5 countries examined, with Canada having the lowest number of brands and active ingredients (28 and 22, respectively) compared to the other countries (Sweden and UK at 67 and 47 brands and 39 and 40 active ingredients, respectively). Not available in Canada are 34 active ingredients (either alone or in combination products) and 5 different types of formulations of HRT. There was a significant difference between the number of combination brand products available in Canada and in the UK (5 versus 29, P <.001, respectively). Canadian women have comparatively few options available to them for the management of menopausal symptoms. The wide range of HRT products available in other developed countries provides alternatives for managing side

Utilisation of hormone replacement therapy in the United Kingdom. A descriptive study using the general practice research database.

To determine prevalence and patterns of hormone replacement therapy (HRT) utilisation in women in the UK. Prospective observational study. UK general practice. Women from general practices throughout the UK. The study period was 1 January 1992 to 31 December 1998. Age-specific prevalence was calculated for each year. Trends in prescribing patterns were described over time. A sub-cohort of 'new starters' on HRT was identified to establish patterns of use, including duration of use and switching of preparations. Characteristics of the sub-cohort were compared with a reference group of non-HRT users. Prevalence, prescribing patterns and differences in characteristics between HRT users and non-HRT users. Among women aged 45-64, prevalence of HRT use increased from 18.6% in 1992 to 27.7% in 1998. Secular trends were observed away from prescribing combined-sequential preparations and towards use of combined-continuous preparations. Among the prescriptions for combined HRT products, only 4.3% contained medroxyprogesterone acetate (MPA). A total of 45.7% of women without a record of a hysterectomy and 53.8% of women with a record of a hysterectomy used HRT for at least three years. When women were partitioned by year of starting HRT, there was a trend of increasing duration of use across the seven years. Some women without a record of a hysterectomy were receiving unopposed oestrogen without progestogen supplementation. Within the past decade, use of HRT has increased among women in the UK with large numbers of women using HRT for long periods and treatment often tailored to the individual.

Managing menopausal symptoms after the women’s health initiative

Until the results of the Women’s Health Initiative (WHI) were released in July 2002, hormone replacement therapy (HRT) had been thought to be the most effective way to manage unwanted menopausal symptoms and to prevent long-term health problems associated with aging. The results of the WHI, showing that HRT is less beneficial and associated with more risks than previously thought, has complicated the management of unwanted menopausal symptoms. This article discusses the effectiveness of HRT and other modalities used to relieve menopausal symptoms and discusses how to choose an HRT product to match specific menopausal complaints and provide maximum safety.

Recent concerns surrounding HRT.

Millions of women are treated with hormone replacement therapy (HRT) for relief of menopausal symptoms, including vasomotor flushes and sweats for which oestrogen is uniquely and highly effective. Others may continue longer-term treatment in the hope that HRT will help to prevent chronic disease. The preservation of bone mass with continuing oestrogen therapy and reduction of subsequent risk of fracture is well established. Observational studies of the metabolic and vascular effects of oestrogens have suggested a potential benefit in reducing the risk of vascular disease, but recently published randomized controlled trials demonstrate no evidence of benefit in women with established vascular disease or in apparently healthy women. The increased risks of breast cancer and thromboembolic disease have been confirmed in these trials, with evidence of increased risk of stroke. Observational data suggest there may be a small increased risk of ovarian cancer associated with longer-term use of HRT. The premature termination of one arm of the Women's Health Initiative randomized controlled trial caused concern among patients, doctors and pharmaceutical companies. There are difficulties in extrapolating the results from trials using a specific HRT product to advise women on the wide range of other hormone products, doses, combinations and routes of administration. However, in the absence of evidence that other products are safer, the data suggest that for many women the risks associated with long-term use of HRT outweigh the benefits. There are nonhormonal strategies for the prevention and treatment of osteoporosis. HRT is not, and has never been, licensed in the UK for the prevention or treatment of vascular disease, and the data suggesting potential benefit should now be regarded as biased. The absolute incidence of an adverse event is low, and the risk in an individual woman in a single year is very small, but the risks are cumulative over time with long-term use. The risk-benefit balance of each woman needs regular reappraisal with continued use.

The Pharmacokinetics of Drug Delivery Systems in Hormone Replacement Therapy

Traditionally, hormone replacement therapy products have administered systemic doses of hormones utilising simple oral delivery. The major disadvantage of oral delivery is that it can lead to deviations from therapeutic targets and, especially if the therapeutic window is narrow, may lead to either reduced efficacy or unwanted side effects. There are now several alternatives to oral delivery of hormones such as transdermal, intrauterine, vaginal, intranasal which are available. These options are usually based on either controlled release or pulsatile delivery. Whilst the benefits of the former are often clear, the physician should always weigh the obvious benefits of controlled drug delivery against those of compliance and patient acceptability. Although sound design principles have been applied to achieve the elegant drug delivery systems now available, many have practical difficulties associated with their chronic use. The methods available will be described.

Effects of norethisterone acetate addition to estradiol in long term HRT

Objective: The aim of this study was to evaluate the efficacy and tolerability of hormone replacement therapy (HRT) among postmenopausal women living in the Lund area of Southern Sweden and to analyze treatment effects in different types or routes of HRT administration, as well as to compare with unopposed estrogen therapy. Method: in an ongoing, large population-based, prospective cohort study, this interim analysis included 3900 women. Of them, 693 postmenopausal women were eligible in the present analyses as they continued to use one of the four commercial HRT products for at least 2–3 years, i.e. continuous oral estradiol (E 2) 2 mg+norethisterone acetate (NETA) 1 mg (CON-O), sequential oral estradiol 2 mg+norethisterone acetate 1 mg (CYC-O), sequential transdermal estradiol 50 μg+norethisterone acetate 250 μg (CYC-TRANS) and estradiol monotherapy. These women completed one generic questionnaire and one specific ‘hormonal’ questionnaire, as well as a personal interview pertaining to sociodemographics, detailed status of HRT use, and therapeutic efficacy and untoward side-effects by HRT. Results: comparing the three combined E 2+NETA groups with E 2 monotherapy, the beneficial effects on sexual desire and emotional well-being were significantly less in the combined groups than in E 2 monotherapy group. There was no significant difference regarding the negative side-effects between the groups. No significant difference was found between CON-O and CYC-O groups either in positive effects or in negative side-effects. A higher prevalence of positive effects was found in CYC-TRANS group than that in CYC-O group, especially in amelioration of sleep and urinary symptoms. Higher odd ratios of negative effects by HRT, such as irregular bleeds, weight gain, food craving and skin disorders were also found in CYC-TRANS group. Conclusion: in long-term HRT administration, the addition of a progestogen in HRT could compromize the beneficial effects of estradiol, particularly, the effects on women's emotional well being and psychosexual functioning. Administration of NETA continuously and sequentially had similar therapeutic efficacy and tolerability. More marked positive effects, such as improving of sleep and urinary symptoms, as well as nuisance side-effects, i.e. irregular bleeds, weight gain, food craving and skin disorders were encountered by the women using sequential transdermal regimen