Endometrial responses to hormone replacement therapy: the bleeding pattern

Little information is available concerning the response of theendometrium to exogenous sex steroid therapy, particularly inthe post-menopausal state. In this study we examined the variabilityof the bleeding pattern in 103 post-menopausal women receivingcyclical sequential combined hormone replacement therapy (HRT)over 6 months. All patients kept menstrual diary cards to recordthe onset, duration and subjective assessment of the severityof bleeding. We defined a cycle as starting from the commencementof treatment till the day of onset of bleeding. Two groups wereidentified amongst 99 women who experienced bleeding: thosewith a mean cycle length of 29 or more days (late bleeders,n = 50) and those with shorter mean cycle length (early bleeders,n = 49). The former were characterized by less variability incycle length and bleeding that was of shorter duration. Fourwomen experienced no bleeding. There were no significant differencesbetween the two groups in age, year since the menopause, weight,height, body mass index (BMI), parity, or in the previous useof HRT. The only significant difference was in their smokinghabits. This suggests a possible link of a hypo-oestrogenicstate to poor cycle control.     

Women's beliefs about "natural" hormones and natural hormone replacement therapy.

OBJECTIVE: To assess women's beliefs about natural hormones, including what they believe the term "natural" means, and their beliefs about the risks, side effects, and efficacy of natural hormone replacement compared to standard hormone replacement. DESIGN: Eighty-two women completed a 20-item survey available at a local compounding pharmacy. Respondents were white (100%), middle-aged (mean age, 47.22 years), and college educated (95.1%); 32.9% were perimenopausal, and 50.0% were postmenopausal; 58.5% were currently using hormone replacement therapy and, of those, 77.1% were using human bio-identical hormones. RESULTS: Ninety percent of the respondents ( n = 74) reported that they had heard about natural hormones. Of those, most believed natural meant plant-derived (44.6%) and/or not synthesized or made without chemicals (50.0%). Most reported hearing about natural hormones from a healthcare provider (66.2%) and/or magazines and books (55.4%). When compared with standard hormone replacement, most respondents endorsed the beliefs that natural hormones have fewer or no risks (71.4%), have fewer or no side effects (69.0%), and are equally or more effective for managing menopause symptoms (61.8%). In addition, many endorsed the beliefs that natural hormone replacement is equally or more effective than standard hormone replacement for protection against osteoporosis (47.1%) and heart disease (40.0%), although many endorsed "don't know" for bone (45.7%) and heart (54.3%) protection. CONCLUSIONS: Among women responding to a survey in a compounding pharmacy, most believed that, compared with standard hormones, natural hormones are safer, cause fewer side effects, and are equally or more effective for symptom management. Many believed natural hormone replacement is equally or more effective for long-term bone and heart protection. Educating women on the nature, risks, and benefits of natural hormone therapy is recommended.     

Women's use of hormone replacement therapy for disease prevention; results of a community survey.

This study investigated whether an increased use of hormone replacement therapy (HRT) is attributable to a growing motivation among women to use the therapy for disease prevention. Compared with earlier studies, results from this community survey of women aged 51 to 57 years revealed an increased use of HRT, 60% of women had tried HRT, with a median of four years' duration of use. The most frequently cited primacy use for HRT was symptom relief although many women also took the therapy for the prevention of osteoporosis. While women generally commence HRT for symptom relief the extended use of the therapy is, in part, likely to be attributable to an increased motivation among women to remain on HRT for its 'added' benefit of preventing osteoporosis.     

Women's anticipations of hormonal replacement therapy

Middle class Caucasian women's anticipations about hormonal replacement therapy (HRT) for perimenopausal symptoms were investigated to expand an understanding of elective use of HRT. This focused ethnography used both interviews and participation in discussion groups established for perimenopausal women as sources of data. Two investigators augmented validity. Inductive and deductive analysis yielded six typologies of anticipations: trusting in nature, fixing, skeptical experimenting, restabilizing, life enhancing, and trusting in science. These findings have clinical and theoretical implications related to issues of non-compliance, health seeking behaviour, provider-recipient interaction, and the focus of scientific investigation.     

Acquired angioedema secondary to hormone replacement therapy

Angioedema is a potentially life threatening condition and may be either inherited or acquired. The latter is rare with only a handful of cases reported in the world literature. Presenting complaints are often vague. Those most commonly described include swelling in the subcutaneous and submucosal tissues. Patients presenting with laryngeal edema have high mortality, and high clinical suspicion is necessary to avoid instrumentation, which can precipitate laryngeal spasm. We present a review of reported cases of hormonally induced hereditary angioedema, along with a report of a patient with acquired angioedema secondary to hormone replacement therapy. To the best of our knowledge, this case probably represents the first reported case of acquired angioedema secondary to hormone replacement therapy.     

Intranasal hormone replacement therapy

Although the optimal route of delivery for hormone replacement therapy has not yet been determined, desirable qualities would include good efficacy, easy administration, minimal side effects, and optimal therapeutic profile. This would potentially serve to improve patient compliance and satisfaction. The intranasal route has been evaluated for the administration of menopausal hormones and seems to fulfill these requirements. The intranasal route would also seem to be a viable alternative for drugs that are poorly absorbed after ingestion by avoiding hepatic first-pass elimination. The intranasal route is, therefore, innovative for the delivery of natural sex steroids in postmenopausal women receiving hormone replacement therapy. Early studies demonstrate that it is safe, effective, and acceptable to postmenopausal women. In addition, the nasal administration of a combination of estradiol and progesterone would seem to be an attractive way to deliver hormones to nonhysterectomized postmenopausal women. Providing alternative routes of administration may also enhance compliance.     

Women's knowledge of hormone therapy.

The aim of this study was to assess women's knowledge of hormone therapy. Two hundred and seven women were interviewed by telephone. The median score to 24 questions concerning the benefits, risks and side effects of therapy was 54.2%. Almost three-quarters of women knew that hormone therapy may decrease the risk of osteoporosis, but half were unaware that it should be taken for at least 10 years for maximum protection against bone loss. While many women knew that hormone therapy may increase the risk of breast cancer, 13.5% believed that it would decrease their risk. Many women overestimated the potential reduction in lifetime risk of hip fracture and the potential increase in lifetime risk of breast cancer with hormone therapy. Women may have insufficient knowledge to make informed choices about hormone therapy. This has implications for physicians who wish to ensure that women are able to participate in informed decision-making.     

The hormone replacement therapy controversy

Summary The issue of hormone replacement treatment for menopausal symptoms, osteoporosis, various cardiac problems, and other disorders has received a great deal of attention. Recent data concerning the benefits and risks have changed ideas about indications and contra-indications. In this paper we will consider the multiple factors that determine an individual woman's decision about taking or continuing to take hormone replacement therapy, not only the medical indications. We will discuss the established benefits of replacement therapy, conditions for which the benefits are not established, areas of controversy, risks of treatment, and factors underlying the decisions about undergoing the treatment.     

Perspectives in hormone replacement therapy

Estrogens have been convincingly shown to be highly effective in preventing and reversing menopause-related conditions, such as hot flushes, urogenital complaints, and postmenopausal bone loss. Observational studies report that long-term, estrogen-containing, postmenopausal hormone replacement therapy (HRT) leads to a substantial reduction in hip fractures, myocardial infarction, and possibly colonic cancer, with important consequences for health and quality of life. Estrogen replacement may postpone the onset of Alzheimer's disease and extend life. While many of these effects are biologically plausible, with a variety of cellular mechanisms being involved, only ongoing and future large-scale randomized clinical trials can and should define the effects of HRT more precisely. Long-term compliance is a key issue for long-term benefits, and offering women a choice of administration routes and regimens can only be beneficial in this respect. Pills, patches, gels, and implants are all widely prescribed. Intravaginal or intranasal forms of administration, which are very easy to use and adaptable on an individual level, are among the new options which could improve long-term continuation of HRT use. Fear of breast cancer and recurrence of vaginal bleeding are real concerns for many women considering HRT. This has led to research into lower-dose, estrogen-containing regimens, into continuous combined regimens, and into the potential of estrogen receptor alpha or beta binding molecules that may help to prevent such problems from arising. The prospects for safe and effective postmenopausal HRT with either estrogens or estrogen-like drugs are very promising when these drugs are used in a patient-tailored, risk profile-based manner.     

National differences in lipid response to postmenopausal hormone replacement therapy

Objective: To compare the response of serum lipids and lipoproteins to the transdermal hormone replacement therapy (HRT) in five European countries. Methods: Five-hundred and sixty-seven healthy postmenopausal women from Belgium, Finland, the Netherlands, Sweden, and the UK received transdermal estradiol 50 μg daily for 12 months. In addition, two groups received transdermally norethisterone acetate (NETA) continuously, two groups sequentially (170 or 350 μg/day); one group received sequentially oral NETA (1 mg/day), and one group dydrogestrone (20 mg/day). Serum total cholesterol, HDL-, HDL2-, LDL-cholesterol, lipoprotein(a) (Lp(a)), and triglycerides were assessed before and at the end of treatment. Results: No significant national differences existed in the pretreatment levels of lipids and lipoproteins. Mean cholesterol, LDL, Lp(a), and triglycerides decreased during HRT, and HDL and HDL2 increased. Individual changes in responses to HRT were strongly dependent on pretreatment values. In this regard, British women differed from the others: their cholesterol, HDL, HDL2, and Lp(a) responses, when related to the pretreatment levels, were smaller than those of the others. Conclusion: A national difference discovered in response of serum lipids to HRT calls for caution in generalization of lipid data from one nation to another during HRT.     

Antidiuretic hormone replacement therapy to prevent or ameliorate vasodilatory shock

Vasodilatory shock is a syndrome with high mortality. It is becoming evident that depletion of antidiuretic hormone (ADH) after cardiac surgery or during sepsis plays an important role in the pathogenesis of this condition. Established vasodilatory shock responds well to exogenous ADH infusion. It is possible that preventing ADH depletion at an earlier stage may abrogate the onset of vasodilatory shock, or at least reduce its severity. This paper examines the evidence supporting this concept, and the potential areas of concern in considering this particular type of hormone replacement therapy.     

Evaluating participants' use of a hormone replacement therapy decision-making intervention

BACKGROUND: Associations between optimal use of a tailored decision-aid and levels of accuracy of perceived breast cancer risk, confidence in decision-making, and satisfaction with decisions about HRT were evaluated in a randomized intervention trial with a community sample of women aged 45-54. METHODS: Data are from 289 women randomized to receive a computer-tailored three-step decision-aid. RESULTS: Forty-seven percent of participants reported optimal use of the intervention materials. African American women and those with low confidence in decision-making were less likely to use the intervention optimally than white women and those with higher confidence (P<0.05). Optimal use of the decision-aid was associated with increased accuracy of perceived risk and confidence to make a decision. DISCUSSION: When used optimally, self-directed decision-aids can improve women's ability to make decisions about HRT. Additional refinement of these aids is needed. For some subgroups of women, adjuncts such as telephone counseling also might be considered.     

The menopause and hormone replacement therapy: views of women in general practice receiving hormone replacement therapy.

Women's views on the menopause and hormone replacement therapy were explored using a questionnaire given to women attending one general practice who were having hormone replacement therapy under the supervision of their doctor. Sixty four women (67%) responded. Although only 5% of women had requested hormone replacement therapy from their general practitioner the majority of women indicated that they had been helped by hormone replacement therapy. Eight per cent of women were using hormone replacement therapy primarily to treat menopausal symptoms with only 6% of women using it primarily as prophylaxis against osteoporosis. Many women were correctly informed about the effects of hormone replacement therapy but mistaken beliefs about its side effects may indicate the need for further health education. The desire for further information was striking: 59% of women wanted further information about hormone replacement therapy, and 80% of women would have liked to have had more information about the menopause before its onset. The media appeared to be an important source of information about health matters: 61% of women obtained information about hormone replacement therapy from either the television, magazines or newspapers. The role of the media and health workers in health education is discussed.     

Endometrial cytology in postmenopausal hormone replacement therapy

Endometrial changes in postmenopausal hormone replacement therapy (HRT) were studied by comparing cytological and histological findings. Cytological and histological examinations were conducted on 138 benign cases and 26 abnormal cases, including 24 cases with disordered proliferative phase (DOP) and 2 cases with simple endometrial hyperplasia (SEH), for a total of 164 cases. Hormones were administered as follows: 1) single cyclic administration of estrogen only (Single-HRT) for 31 cases, 2) cyclic administration of estrogen and progestin (Cyclic-HRT) for 105 cases, and 3) continuous administration of estrogen and progestin (Continuous-HRT) for 28 cases. All of the 164 cases were studied cytologically as to shape, appearance, nuclear number on maximum diameter, and so on. The benign cases in each mode of administration as described above revealed the following: 1) Single-HRT, atrophy or the proliferative phase was noted histologically, and the copresence of the endometrial epithelium and the ciliated cell metaplasia was observed cytologically; 2) Cyclic-HRT, the first half of the administration term was of the proliferative phase histologically, and the linear and long glands were seen cytologically. In the latter half of the administration term the secretory phase was noted histologically and the curved/linear glands with subnuclear vacuolization were observed cytologically; and 3) Continuous-HRT, atrophy was noted histologically, and fewer glands and atrophic cells on the endometrial epithelium with wrinkles mixed therein were seen cytologically. On the other hand, cytological examinations of the abnormal cases revealed a mean average of 35 nuclei on the maximum diameter of the gland, protrusion and/or ramification of the glands, densely clustered glands, and back-to-back glands without fusion, as well as irregularly dilated tortuous glands in SEH. These abnormal findings were considered useful for early detection of endometrial disorders in the hormone replacement therapy by cytodiagnosis. Diagn. Cytopathol. 1998;19:161–167. © 1998 Wiley-Liss, Inc.