Start Of Hormone Replacement Therapy Research Articles

Premature ovarian insufficiency in patients with galactosemia

Background. Galactosemia is a congenital disorder of carbohydrate metabolism caused by a defect in any of the enzymes of galactose metabolism. One of the long-term complications is premature ovarian insufficiency (POI), which is more common in patients with the c.563A>G (Q188R) mutation in the homozygous state in the galactose-1-phosphate uridylyltransferase (GALT) gene. At the same time, fertility factors may be higher in patients with POI caused by classical galactosemia (CG) compared with other causes of POI, which makes it difficult to resolve the issue of the need to use fertility preservation methods for this group of patients in the prepubescent period. Case report. This article describes two clinical observations of patients with CG who were diagnosed with hypergonadotropic hypogonadism. Patient A. was initiated hormone replacement therapy (HRT) at the age of 11, and according to the results of osteodensitometry, there is currently no decrease in bone mineral density. In patient C. at the age of 14, before the start of HRT, ovaries without pronounced follicular apparatus, osteopenia and osteoporosis were detected. The issue of the necessity and timing of the use of fertility preservation methods is being considered. Conclusion. Patients with CG are recommended to monitor hormonal profile indicators for timely administration of HRT. Cryopreservation of ovarian tissue should be considered as one of the options for maintaining fertility in patients with CG, taking into account that some of them still have the possibility of spontaneous pregnancy, despite the POI.

Transgender Women on Estrogen Have a Lower Burden of Thrombotic Events Compared to Cisgender Men: A Nationwide Hospital-Based Survey

Due to public recognition and acceptance, more transgender women are being prescribed gender-affirming estrogen therapy. Traditionally, sexual dimorphism has been shown to play a significant role in the pathophysiology of thrombotic phenomena. While genetic factors remain the key players in the divergent male and female phenotypes, limited information is available regarding the thrombo-vascular effects of estrogen therapy in transgender women. Furthermore, available data has been conflicting with respect to vascular outcomes in this specific population. Therefore, more evidence is required to understand the long-term effects of gender-affirming estrogen therapy. In the current study, we investigated the thrombotic outcomes of estrogen therapy in transgender women (male sex assigned at birth), in comparison to cisgender men and cisgender women. We performed retrospective analyses using the TriNetX database that includes de-identified data for over 250 million patients across 76 certified healthcare organizations. We included all adults over the age of 18 years and excluded those with the presence of documented prothrombotic risk factors such as obesity, diabetes, hyperlipidemia, smoking, and cancer. Within the cohort of cisgender women, we excluded pregnancy and post-menopausal status. The thrombotic outcomes within the transgender cohort were recorded after the start of hormone replacement therapy. To account for thrombotic events, we used search terms such as acute myocardial infarction (MI), cerebral infarcts, pulmonary embolism (PE), and deep vein thrombosis (DVT). We found 12,369 transgender women, 29,746,302 cisgender men, and 32,591,972 cisgender women that were eligible for our study. The transgender women had lower incidences of MI (0.14% vs. 0.38%, P<0.0001), cerebral infarcts (0.21% vs. 0.49%, P<0.0001), and DVT (0.33% vs. 0.47%, P<0.022) compared to cisgender men. The incidence of PE was comparable in both these groups (P=0.85). Furthermore, we observed that transgender women also experienced significantly lower incidences of cerebral infarcts (0.21% vs. 0.42%, P=0.0003) and a moderately decreased incidence of MI (0.14% vs 0.22%, P=0.062) compared to cisgender women. The incidence of venous thrombosis was similar in these two groups. Overall, we observed a paradoxical decrease in rates of thrombotic events, suggesting that estrogen may play a protective role against the development of acute MI, cerebral infarction, and DVT in transgender women. Further investigation is required to understand the downstream targets that offer these cardioprotective effects. Importantly, our data may provide clinicians with reassurance that traditional vascular risks associated with estrogen may be less pronounced in males.

Sheehan’s syndrome with hypothyroidism: a rare case report

Sheehan's syndrome is a form of hypopituitarism caused by pituitary gland necrosis caused by hemorrhagic shock during pregnancy. It's a rare issue with a wide range of symptoms and a long time to diagnose. A 40-year-old female presented with a giddiness which was rotatory type followed by headache, vomiting associated with nausea, decreased appetite for one week. She has experienced excessive vaginal bleeding and secondary amenorrhea exists for 20 years. Patients diagnosed to have acute liver injury, hyponatremia, and acute gastritis. The thyroid profile showed hypothyroidism and the patient started on appropriate medication. Hypopituitarism due to Sheehan's disease was discovered after a thorough clinical examination, endocrine investigations, and a pituitary magnetic resonance scan. Following the start of hormone replacement therapy, she showed significant improvement. The current case demonstrates that undiagnosed Sheehan's syndrome is linked to long-term morbidity, and we want to emphasize the importance of a high index of suspicion for early diagnosis of the syndrome during routine clinical visits to avoid complications that can arise from delayed diagnosis.

Diagnosis of Male Central Hypogonadism During Childhood.

The diagnosis of male central (or hypogonadotropic) hypogonadism, typically based on low luteinizing hormone (LH) and testosterone levels, is challenging during childhood since both hormones are physiologically low from the sixth month until the onset of puberty. Conversely, follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH), which show higher circulating levels during infancy and childhood, are not used as biomarkers for the condition. We report the case of a 7-year-old boy with a history of bilateral cryptorchidism who showed repeatedly low FSH and AMH serum levels during prepuberty. Unfortunately, the diagnosis could not be ascertained until he presented with delayed puberty at the age of 14 years. A gonadotropin-releasing hormone (GnRH) test showed impaired LH and FSH response. By then, his growth and bone mineralization were partially impaired. Gene panel sequencing identified a variant in exon 15 of FGFR1, affecting the tyrosine kinase domain of the receptor, involved in GnRH neuron migration and olfactory bulb morphogenesis. Testosterone replacement was started, which resulted in the development of secondary sexual characteristics and partial improvement of bone mineral density. This case illustrates the difficulty in making the diagnosis of central hypogonadism in boys during childhood based on classical criteria, and how serum FSH and AMH assessment may be helpful if it is suspected before the age of puberty, and confirm it using next-generation sequencing. The possibility of making an early diagnosis of central hypogonadism may be useful for a timely start of hormone replacement therapy, and to avoid delays that could affect growth and bone health as well as psychosocial adjustment.

The dynamics of the electrophysiological parameters of hands nervous during hormone replacement therapy in patients with newly diagnosed hypothyroidism

To clarify the pathogenesis of neuropathy in 20 patients with newly diagnosed primary (thyrogenous) hypothyroidism in the background of autoimmune thyroiditis electroneuromyographic study of hand nerves before and after the start of hormone replacement therapy was conducted. At the beginning of the study, all patients were diagnosed with manifest hypothyroidism. The serum levels of thyroid stimulating hormone were elevated, and the concentration of free thyroxin was reduced. At the end of the study (after 6 months), the concentration of thyroid stimulating hormone and free thyroxine in the blood serum were within reference values, which indicated the effectiveness of treatment of hypothyroidism. During electroneuromyographic examination before treatment in 5 patients were recorded normal levels compared to normative data by age and sex. In 15 recorded the data for violation of the sensory fibers. Data for breach of conduct has not been received by the motor fibers. After 6 months of starting hormone replacement therapy data for violation of the sensory and motor fibers had been received from 14 of 20 patients. 6 noted the positive dynamics of electroneuromyography. The lateralization of the severity of the lesions of the nerve fibers depended on the leading arm. Thus, the decrease in the amplitude of the sensory potential of the median was more pronounced in the right, leading arm. For the ulnar nerve, this dependence of the lateralization of the lesion was not detected.
 With this stimulus electroneuromyography been identified primary lesion of nerves and clarify the role of the effect of hormone replacement therapy on the development of neuropathies.

Drospirenone plus estradiol and the risk of serious cardiovascular events in postmenopausal women

Objectives: To compare incidence rates of serious cardiovascular events, particularly arterial thromboembolic events (ATE), in users of hormone replacement therapy (HRT), particularly oral continuous combined preparations.Methods: Prospective, controlled cohort study with four arms: women using (1) drospirenone (DRSP)/estradiol, (2) other oral continuous combined HRT (HRTcc), (3) all other oral HRTs, and (4) non-oral HRT. The study population consisted of women aged 40+ years in seven European countries who were new users of HRT at the time of inclusion. All patient-reported outcomes of interest were validated by the treating physicians. A multifaceted, four-level follow-up procedure ensured low loss to follow-up rates. The final analysis is based on Cox regression models comparing the cohorts.Results: In total, 30 597 women were recruited by 1052 study centers. Follow-up reflects 101 715 woman-years of observation. Loss to follow-up was about 2.8%. Risk estimates for general serious adverse events were similar for all cohorts. Incidence rates for serious cardiovascular events were 98.4 (DRSP/estradiol) and 169.7 (HRTcc) per 10 000 woman-years. The corresponding incidence rates for ATE were 10.9 and 29.7 events per 10 000 woman-years with an adjusted hazard ratio of 0.5 (95% confidence interval 0.3–0.8). The initiation rate for antihypertensive treatment after start of HRT was substantially lower for women using DRSP/estradiol compared to the other cohorts.Conclusions: DRSP/estradiol is associated with general health risks similar to other oral and non-oral HRT but is probably associated with lower ATE risk.Clinical trial registration: NCT00214903, US National Library of Medicine.

Childhood growth of females with Kallmann syndrome and FGFR1 mutations.

In search of phenotypic cues that would allow early detection of Kallmann syndrome (KS), we evaluated the paediatric phenotypes in a series of females with KS. In this retrospective cohort study, we investigated childhood growth in six females with KS due to mutations in FGFR1 and evaluated their reproductive phenotypes later in life. While growth during early infancy and childhood was within normal limits, a decreasing trend in height SDS already from mid-childhood occurred in most patients. The lowest height SDS (mean, -1·2 SDS) occurred between 14 and 15 years of age, before the start of hormone replacement therapy. As adults, these women required assisted reproductive techniques for fertility. One of the probands passed on her G48S mutation to her son, who showed normal reproductive hormone levels during the minipuberty of infancy. Early diagnosis of female KS remains a challenge as early phenotypic signs, apart from anosmia, are scarce. Females with KS exhibit a slight reduction in growth rate during mid-childhood, but normal growth rate during the minipuberty of infancy, despite congenital lack of ovarian oestrogen. Women harbouring FGFR1 mutations will have 50% chance of passing on the gene defect to their offspring. We recommend genetic counselling to all females with KS to be carried out as a part of family planning.

Postmenopausal sex hormones: comparing apples and pears

Postmenopausal sex hormones: comparing apples and pears

Uterine development in patients with Turner syndrome: Relation to hormone replacement therapy and karyotype

Our study aimed to assess uterine development in Turner syndrome patients and its relation to dose and type of estrogen therapy; and karyotype. Pelvic ultrasound was used to assess uterine size and shape, and ovarian volume in 40 Turner syndrome patients. Information on hormone replacement therapy was collected from patients' notes. Among the 40 patients studied, 57.5% started estrogen therapy and 30% were taking progestins. Sixty-five per cent had immature uterus, 17.5% had fully mature uterus and 17.5% had transitional uterus. Uterine volume was associated with age (p < 0.001), height (p = 0.002), weight (p = 0.001), years of estrogen use (p < 0.001), estrogen dose (p = 0.016), current estrogen use ( p =0.001) and Tanner breast stage ( p <0.001). Uterine volume was not affected by the type of estrogen used ( p =0.40) and karyotype ( p =0.40). Patients with Turner syndrome treated with estrogen (of adequate dose and duration) may attain a normal, mature uterine size and configuration, even at a late start of hormone replacement therapy and regardless of karyotype.

Influence of habitual physical activity on body composition, fat distribution and metabolic variables in early postmenopausal women receiving hormonal therapy

Objective To determine whether there is an association between the level of habitual physical activity, body composition and anthropometric and metabolic variables in postmenopausal patients before and after hormone replacement therapy (HRT). Study design Thirty-four healthy, recent postmenopausal women (50 ± 2.7 years; 23.8 ± 10 months since menopause) consulting for symptoms of estrogen deficiency were included in the study. Anthropometric assessment, percent of body fat (BF) estimated by skinfold measures, and metabolic evaluation were performed before and 4 months after the start of HRT, which included non-oral or low-dose oral preparations. The status of physical activity was defined by counting steps with a pedometer. Patients were stratified as active (6000 steps ore more per day) or inactive (fewer than 6000 steps per day). Results are expressed as mean ± SD or median and interquartile range. log 10 transformation was used to normalize the distribution of non-Gaussian variables. ANOVA for repeated measures was performed for the active and inactive groups, before and after HT. Pearson correlation coefficient was used to investigate the relationship between anthropometric and metabolic variables and habitual physical activity. Results BMI and BF did not change with HRT in comparison with baseline. In contrast, a decline was observed in waist circumference (WC) and waist to hip ratio (WHR) after HRT in both active and inactive women ( P < 0.01). While triglycerides and glucose did not change after HRT, total and LDL-cholesterol decreased from baseline. In contrast, after HRT, active patients were found to have lower BF than inactive women (active: 25.4 ± 2.5; inactive: 26.6 ± 2, P = 0.01). There was a significant negative correlation between habitual physical activity (number of steps per day) and BF ( r = −0.36, P = 0.04). After HRT, when only active patients were considered, a significant negative correlation was found between the number of steps and WC ( r = −0.42, P = 0.04) and WHR ( r= −0.58, P = 0.03). Conclusion Habitual physical activity plays a major role in preserving a favorable cardiovascular profile in postmenopausal patients using HRT.

Coronary heart disease and HRT in France: MISSION study prospective phase results

Objective. To determine the morbidity incidence associated with Hormone Replacement Therapy (HRTs) in postmenopausal women. This paper presents the results concerning the incidence of coronary heart disease (CHD).Design. MISSION study started on 5 January 2004, the cutoff for data collection was June 2006 (follow-up no. 1). ‘Exposed group’: postmenopausal women currently on HRT, commonly prescribed in France or stopped ≤5 years previously. ‘Unexposed group’: never received HRT or stopped >5 years previously.Results. Data were available for 4949 patients (without CHD at the beginning of the follow-up): 2693 Exposed group and 2256 Unexposed group. The incidence during follow-up no. 1 of postmenopausal CHD was not significantly different in the Exposed group (0.11%) compared with the Unexposed group (0.13%). In the Exposed group the time between start of HRT and menopause was 2.93 ± 4.46 years in those who experienced CHD and 1.53 ± 3.20 years in those who had no incidence of CHD (p = 0.3).Conclusion. In the MISSION cohort, no increased risk of CHD was found in the Exposed group compared with the Unexposed group

Issues concerning the use of hormone replacement therapy and risk of fracture: a population‐based, nested case‐control study

To investigate the effect of duration, how recently it has been used, and age at start of hormone replacement therapy (HRT) and the risk of bone fracture. A population-based, nested case-control study was conducted in Lombardia, Northern Italy. The 78,294 women aged 45-75 years who received at least one HRT prescription during 1998-2000 were followed until 2005. Cases were women who experienced bone fracture during follow-up. Up to six controls were randomly selected for each case from the cohort after matching for age and date of cohort entry. The odds ratio of fracture associated with the use of HRT was estimated by conditional logistic regression. One thousand one hundred and seventy-four cases and 6760 controls were included. Compared with women who took HRT for less than 2 months, those who were treated for more than 20 months had an odds ratio (OR) of 0.80 (95% confidence interval 0.65, 0.99). This risk reduction was still significant among current HRT users (OR 0.71, 95% CI 0.55, 0.90) and in women who began therapy at the age of 55-65 years (OR 0.63, 95% CI 0.42, 0.94) or 65-75 years (OR 0.56, 95% CI 0.32, 0.99). There was no statistical evidence of a protective effect for women who had stopped treatment more than 6 months previously or those who began HRT at the age of 45-55 years. HRT should be continued for long periods to achieve an optimal protection from fracture. The fracture reducing potential of HRT seems to disappear after a few months without treatment and might mainly act in women who begin therapy at older age.

Conjugated estrogen plus medroxyprogesterone does not impair blood rheological properties in hypertensive postmenopausal women

Objectives Hypertension and estrogens are both prothrombotic. We used the microchannel method to investigate whether hormone replacement therapy (HRT) with conjugated equine estrogen (CEE) plus medroxyprogesterone acetate (MPA) affects blood flow through the microchannels in hypertensive postmenopausal women being treated with antihypertensive drugs and in normotensive postmenopausal women. Methods Sixty-two consecutive postmenopausal women were randomly assigned to a hypertensive HRT group ( n = 16), hypertensive control group ( n = 15), normotensive HRT group ( n = 16) and normotensive control group ( n = 15). Each HRT group received CEE 0.625 mg plus MPA 2.5 mg daily orally for 12 months. Both hypertensive groups were being treated with antihypertensive drugs before the study. Microvascular blood flow was assessed on the basis of blood passage time, the time required for 100 μl of whole blood to pass through a cylinder, was determined before and 12 months after the start of HRT by the microchannel method (micro channel array flow analyzer). Results CEE plus MPA therapy did not change blood passage time in any of the groups. Microscopic observation showed that the whole blood passed smoothly through the microchannels in every group. Conclusions CEE plus MPA therapy may not impair blood flow through the microchannels in hypertensive postmenopausal women receiving antihypertensive drugs or in normotensive postmenopausal women. However, administration of CEE plus MPA to postmenopausal women with hypertension warrants caution against the occurrence of thromboembolic events.

Effects of hormone replacement therapy on serum angiotensin-converting enzyme activity and plasma bradykinin in postmenopausal women according to angiotensin-converting enzyme-genotype.

An insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene determines serum ACE levels. The D allele is associated with increased ACE activity and is linked to cardiovascular disease. Hormone replacement therapy (HRT) in postmenopausal women (PMW) decreases serum ACE activity and concomitantly increases plasma bradykinin. We investigated the effect of HRT on these parameters in PMW according to ACE-genotype. We assessed 68 PMW during 12-month oral HRT (0.625 mg conjugated estrogen +2.5 mg medroxyprogesterone acetate). ACE genotype was determined at baseline, and serum ACE activity and plasma bradykinin were measured at baseline and after 3-, 6-, and 12-month HRT. We divided the PMW into three groups according to ACE genotype: groups I/I (n = 26), I/D (n = 33), and D/D (n = 9). HRT resulted in a significant reduction in the genotype-associated increase in ACE activity in the ACE I/D and D/D groups after 6-month (p < 0.001 and p < 0.05, respectively) and 12-month HRT (p < 0.001 and p < 0.01, respectively), but not in the I/I group. While the reduction of ACE activity was expected to increase bradykinin in the ACE I/D and D/D groups, HRT significantly increased the bradykinin levels not only in these two groups but also in the ACE I/I group at both 6 months (p < 0.01, p < 0.05, and p < 0.001, respectively) and 12 months after the start of HRT (p < 0.01, p < 0.01, and p < 0.01, respectively). These results suggest that the increased plasma bradykinin of PMW by HRT might not be induced solely by the reduction in serum ACE activity.

Hormone replacement therapy and chronic graft-versus-host disease activity in women treated with bone marrow transplantation for hematologic malignancies.

Several lines of experimental evidence suggest that sex hormones may influence the development and activity of chronic graft-versus-host disease (cGVHD), which frequently occurs in patients undergoing allogeneic bone marrow transplantation (ABMT). Following ABMT, young women are commonly treated with hormone replacement therapy (HRT) because of irreversible gonadal failure. It seemed therefore worthwhile to investigate the effects of this therapy on the activity of cGVHD. Premenopausal women treated with ABMT for hematological malignancies between January 1997 and December 2000 were evaluated for cGVHD activity. They were divided into two groups, depending on whether or not they were treated with HRT. Seventy-one women qualified for the present study: 39 received HRT (treated group), while 32 did not (controls). In both groups of patients, cGVHD activity score was comparable before the start of HRT. No differences were observed in cGVHD activity score between the HRT group and controls after 3, 6, 12, and 24 months from the start of HRT. Furthermore, HRT did not induce any increase in the cGVHD activity score in the treated group of patients at any time from the start of HRT. According to present data, HRT did not appear to influence the activity of cGVHD in young women who underwent ABMT for hematological malignancies. Therefore, we can safely propose this therapy for women with gonadal failure after ABMT.

Mammographic density changes during different postmenopausal hormone replacement therapies

Objective: To determine the degree of change in mammographic breast densities during different types of postmenopausal hormone replacement therapies. Design: A retrospective study. Setting: Ege University Hospital. Patient(s): The mammographies of 216 women on various postmenopausal hormone replacement therapies were evaluated. Intervention(s): Estrogen alone (n = 76) or estrogen in cyclic (n = 44) or continuous (n = 61) combination with progestin or tibolone-only (n = 35) replacement therapies were used. Mammographic density was quantified according to the Wolfe classification in patients with different hormone replacement regimens. Main Outcome Measure(s): Mammographic density changes were interpreted. Result(s): An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy 31.1% (19 of 61) than among those receiving estrogen-only 3.9% (3 of 76) treatment. There were no significant mammographic breast density changes among women receiving cyclic continuous combination hormone replacement therapy or tibolone-only treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. In continuous combined postmenopausal hormone replacement therapy with norethisterone acetate, the increase in mammographic density was 34.1% (15 of 44), followed by medroxyprogesterone acetate 23.5% (4 of 17). Conclusion(s): Our findings show that mammographic breast density changes related to postmenopausal hormone replacement therapy are dependent on the selected hormone regimen. The continuous administration of the progestin component of the combined-hormone replacement therapy seems to effect the breast density most.

Hormone replacement therapy and bone metabolic marker

With the advent of newly developed sensitive markers of bone turnover, initial values of biochemical markers were reported to be significantly higher in those that gained bone than in those that lost bone in hormone replacement therapy (HRT) . Bone resorption markers reach nadir 3 to 6 months after the start of HRT whereas bone formation markers reach nadir 6 month after the treatment. The greater the decrease in biochemical markers is, the larger the bone mass can be expected to be obtained with HRT.

Randomized comparison between orally and transdermally administered hormone replacement therapy regimens of long-term effects on 24-hour ambulatory blood pressure in postmenopausal women

Objective: The aim of this study was to assess whether oral delivery and transdermal delivery of sequential combined hormone replacement therapy have similar effects on systemic blood pressure, as measured by 24-hour automated ambulatory recordings. Study Design: Eighty-two healthy postmenopausal women, of whom 73 completed the study, were randomly assigned to start hormone replacement therapy with either orally (n = 38) or transdermally (n = 35) administered medication. Ambulatory blood pressure was recorded for a 24-hour period before the start of hormone replacement therapy and again 2 and 6 months later. Analysis of variance was used for data analysis. Results: Hormone replacement therapy by both oral and transdermal routes was associated with slight but nonsignificant drops in mean 24-hour systolic and diastolic ambulatory blood pressure. Daytime systolic ambulatory blood pressure (mean ± SE) fell significantly (P <.05) and similarly at 2 months in the oral (3.8 ± 0.2 mm Hg) and transdermal (4.0 ± 0.3 mm Hg) treatment groups. The daytime ambulatory blood pressure remained significantly lower than baseline at 6 months in the oral treatment group (–3.6 ± 0.3 mm Hg), whereas the fall at 6 months in the transdermal group (–3.1 ± 0.3 mm Hg) was not significant. Mean daytime diastolic ambulatory blood pressure was reduced in both the oral (–1.8 ± 0.8 mm Hg) and transdermal (–3.5 ± 0.7 mm Hg; P <.05) treatment groups at 2 months but not at 6 months. Nighttime ambulatory blood pressures in both groups remained unaffected by hormone replacement therapy. Conclusion: Sequential combined hormone replacement therapy delivered by both oral and transdermal routes caused significant falls in the daytime ambulatory blood pressure of normotensive postmenopausal women at 2 months of treatment. This fall persisted as long as 6 months of treatment in the oral treatment group but not in the transdermal treatment group. (Am J Obstet Gynecol 2001;184:904-9.)

Mammographic breast density during hormone replacement therapy: Differences according to treatment

Objective: Our purpose was to investigate the effects of various hormone replacement regimens on mammographic breast density. Study Design: Mammographic density was recorded in women participating in a population-based screening program. All women were nonusers of hormone replacement therapy at first mammogram and thereafter reported continuous use of the same treatment: estrogen alone (n = 50) or estrogen in cyclic (n = 75) or continuous (n = 50) combination with progestogen. Mammographic density was quantified according to the Wolfe classification. Results: An increase in mammographic density was much more common among women receiving continuous combination hormone replacement therapy (52%) than among those receiving cyclic (13%) and estrogen-only (18%) treatment. The increase in density was apparent already at first visit after the start of hormone replacement therapy. There was little change in mammographic status during long-term follow-up. Conclusion: Regimens of hormone replacement therapy were shown to have different effects on the normal breast. There is an urgent need to clarify the biologic nature and significance of a change in mammographic density during treatment and, in particular, its relation to symptoms and breast cancer risk. (Am J Obstet Gynecol 1999;181:348-52.)

Effect of hormone replacement therapy on salivary flow rate, buffer effect and ph in perimenopausal and postmenopausal

The effects of hormone replacement therapy (HRT) on salivary gland functions were examined in a longitudinal study. The flow rate, buffer effect and pH of paraffin-stimulated whole saliva were analysed in 8 perimenopausal and 19 postmenopausal women. The saliva samples were collected 1–2 days before as well as 3 and 5 months after the start of HRT. Salivary flow rates were higher ( p < 0.033) in the perimenopausal than in the postmenopausal group. The flow rates increased significantly ( p < 0.001) during HRT in both groups. Similarly, buffer effect and pH showed significant ( p = 0.004andp = 0.009, respectively) time-related changes without any differences between the groups. It appears that HRT improves both the quantity and the quality of salivary gland function in peri- and postmenopausal women.