Estrogen-progesterone Therapy Research Articles

Case Series: Severe meibomian gland loss in polycystic ovarian syndrome patients on estrogen-progesterone therapy: A case series

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

Use of hormones and risk of venous thromboembolism.

•The risk of venous thromboembolism (VTE) is not increased in women using long-acting reversible contraceptive methods (LARCs) with progestogens. •Oral contraceptives with levonorgestrel or norgestimate confer half the risk of VTE compared to oral contraceptives containing desogestrel, gestodene or drospirenone. •Progestogen-only pills do not confer an increased risk of VTE. •Women using transdermal contraceptive patches and combined oral contraceptives (COCs) are at an approximately eight times greater risk of VTE than non-users of hormonal contraceptives (HCs), corresponding to 9.7 events per 10,000 women/years. •Vaginal rings increase the risk of VTE by 6.5 times compared to not using HC, corresponding to 7.8 events per 10,000 women/years. •Several studies have demonstrated an increased risk of VTE in transgender individuals receiving hormone therapy (HT). •Hormone therapy during menopause increases the risk of VTE by approximately two times, and this risk is increased by obesity, thrombophilia, age over 60 years, surgery and immobilization. •The route of estrogen administration, the dosage and type of progestogen associated with estrogen may affect the risk of VTE in the climacteric. •Combined estrogen-progesterone therapy increases the risk of VTE compared to estrogen monotherapy. •Postmenopausal HT increases the risk of thrombosis at atypical sites.

Hormone replacement therapy and breast cancer incidence in Korean women

ObjectivesAfter the 2002 Women's Health Initiative (WHI) study, the global use of menopausal hormone therapy (MHT) declined, and despite subsequent studies indicating a low risk of breast cancer, concerns about MHT usage persist. We examined the relationship between changes in MHT use and changes in the incidence of breast cancer from 2002 to 2020 in South Korea. Study designThis study used tumor registry information from 2002 to 2020 from the Korean Statistical Information Service and analyzed the incidence rate of invasive breast cancer in women, who were divided into two age groups: <50 and >50 years. The numbers of MHT prescriptions in Korea between 2002 and 2020 was determined from pharmacy data. ResultsThe incidence of breast cancer per 100,000 women in South Korea increased from 34.3 in 2002 to 96.4 in 2020. Breast cancer incidence rates increased annually in both groups of women (those aged under and over 50 years), with no significant difference between the two (p = 0.614). Prescriptions for estrogen therapy (ET) in 2020 were 52.7 % lower than those in 2002. Prescriptions for estrogen-progesterone therapy (EPT) decreased by 27.9 % over the same period. Conversely, tibolone prescriptions, which had initially decreased by 25.4 % in 2004, subsequently showed a steady increase and were 93.6 % higher in 2020 than in 2002. ConclusionThe incidence of breast cancer increased annually in Korean women of all ages; however, the use of ET and EPT for MHT has declined since 2002, particularly the use of EPT after 2010. MHT, especially EPT, did not significantly increase the incidence of breast cancer in Korean women.

Relationship between menopausal hormone therapy and incidence of fractures in postmenopausal women

Objective Long-term protective effects of menopausal hormone therapy (MHT) at fractures with different doses and components are controversial. We analyzed the effect of MHT on the incidence of spine and femur fractures according to MHT type, age at commencement, duration and dose of hormones in Korean women. Method This retrospective study evaluated propensity score-matched patients with MHT from the Korean National Health Insurance Service database. Among women aged ≥50 years with menopause between 2004 and 2007, spine and femur fracture incidence until 2017 was analyzed in 36,446 women who had received MHT for >1 year. Estrogen–progesterone therapy (EPT), estrogen-only therapy (ET) or tibolone therapy was conducted. Results EPT significantly lowered the incidence of spine and femur fractures with a conventional dose, but not with a low dose. Tibolone significantly decreased the incidence of spine fractures in women aged 50–59 years when used for >5 years, and the incidence of femur fractures in women older than 60 years when used for >3 years. ET significantly lowered the risk of femur fractures when estradiol was used for >5 years. Conclusion In menopausal women, all MHT including conventional-dose EPT, ET and tibolone tended to lower the incidence of fractures. The effects, however, varied with the type of fracture and type of MHT.

Severe meibomian gland loss in polycystic ovarian syndrome patients on estrogen-progesterone therapy: A case series.

Purpose: To report the ocular surface and meibomian gland changes in polycystic ovarian syndrome (PCOS) women taking hormone supplementation. Methods: Case series. Results: Three women (27 ± 11 years) already diagnosed with PCOS presented with dry eye symptoms (mean OSDI, 37.5) for a mean duration of 13 months and were taking hormonal supplements for a mean duration of 60 ± 11 months. The hormonal supplements included oral estrogen (n=3), oral progesterone (n=3), antiandrogen cyproterone (n=1) and isotretinoin (n=1). Ocular surface evaluation revealed mean NIBUT of 9.9 ± 1.6 seconds and mean TMH of 0.27 ± 0.05 mm, assessed non-invasively using Oculus keratograph 5M (K5M). Meibography (K5M) showed near total loss of all meibomian glands (n=8/12 eyelids) with residual ghost glands in all four eyelids of two patients, and gland shortening alone in one patient. The gland morphology did not change following intense thermal pulsation treatment or cessation of hormonal therapy. Conclusions: Near-total irreversible meibomian gland loss was seen in two young PCOS women taking hormonal supplements. Collaboration between ophthalmologists and gynecologists is advisable for early detection and better understanding of dry eye disease (DED) progression in these patients.

EARLY DIAGNOSIS OF HYPERTENSIVE DISEASE IN YOUTH WITH NORMAL SYSTOLIC AND DIASTOLIC BLOOD PRESSURE LEVELS

Objective: Hypertensive cardiovascular disease can develop functional and/or structural organ damage by the increase of the volume/pressure and arterial stiffness, even before the current cut-off level of the systolic/diastolic blood pressure. The aim of this study was to evaluate in a young population with normal blood pressure levels if they presented any cardiovascular risk factors, arterial stiffness, signs, and symptoms of hypertensive disease. Design and method: This is a retrospective cross-sectional study developed between the years 2007/2022 from 9,600 non-invasive applanation tonometry, females-males 200-103 were entered, with an age range of 18 and 30 years old, and an average age of 24 years. Patients made their first cardiology visit without a previous diagnosis of arterial hypertension or decompensated associated diseases with a blood pressure not higher than 130/80 mmHg. Anthropological data, systolic/diastolic blood pressure, and heart rate were registered. Central Haemodynamics Parameters were measured with a SphygmoCor-PVX device (AtCor, Australia), a validated system employing the high-fidelity technique of applanation tonometry according to established protocols. Results: The average systolic/diastolic blood pressure among female-male was 112.9/72.4 mmHg-119.8/73.9 mmHg, respectively. Also, the Central Aortic Pressure in the female-male groups was 100.0 mmHg/103.7 mmHg, while the maximum values are 101.5 mmHg/106.0 mmHg, but the differences between the observed values and the normal levels of the Augmentation Index (a surrogate measure of arterial stiffness) were higher than normal in female-male 3.6%-4.6% indicating an incipient arterial stiffness. Into the female-male groups, were observed hyperlipidemia 10%-10%, smoking 26%-20%, minimal-mitral regurgitation 5%-8%, headache 46%-26%, palpitations 33%-25%, asthenia 22%-14%, sweating 9%-14%, and chest-pain 16%-27%, respectively. The percentage of women who had a history the polycystic ovarian syndrome was 19%, and the women in current or former estrogen-progesterone therapy were 17%-12%, respectively. Among the female-male groups that do not register any risk factor, symptoms, signs, or arterial stiffness were 8.5%-10%. Conclusions: In young people with normal blood pressure values, it is important to know the risk factors, symptoms, signs, and arterial stiffness of hypertensive disease for early diagnosis and to be able to optimize the time to start therapy.

ODP035 Congenital Adrenal Hyperplasia secondary to 3 beta hydroxydehydrogenase deficiency: Case study and review of literature

Abstract Introduction Congenital Adrenal Hyperplasia (CAH) results from one of the five steroidogenic hormonal deficiencies in adrenal steroid synthesis pathway, most commonly caused by 21-hydroxylase deficiency (21-OHD). 3β-hydroxysteroid dehydrogenase (3βHSD) deficiency (def) is very rare cause of CAH, accounting for less than 0.5% of the CAH cases, associated with disorder of sexual development (DSD) and steroidogenesis. We present a case of salt wasting CAH secondary to 3βHSD-def with focus on the management compared with 21-OHD. Case 53yr white female who was diagnosed with salt wasting CAH at birth, started on hydrocortisone replacement. She had oophorectomy at age of 11 due to hemorrhagic changes in ovaries. She was placed on oral contraceptives for most of her life. Her family history is significant for CAH in all of her 3 sisters, with oldest sister having pubic hair at age of 2 with frequent illnesses, triggering extensive workup and was subsequently diagnosed with CAH. Two brothers were also diagnosed with CAH with complete scrotum bifurcation at birth. Her family was subsequently diagnosed with 3βHSD deficiency. Patient's ACTH, Renin, 17-Hydroxyprogesterone (17-OHP) levels have been fluctuating due to skipping of hydrocortisone doses on occasions. Her sleep pattern remains disturbed, going to bed 3-4 AM and waking up at 2-3 PM. Discussion 3βHSD deficiency is very rare cause of CAH with prevalence less than 1 in million cases at birth. First cases were reported by Bongiovanni in 1962. It is autosomal recessive disorder affecting both the sexes. 3βHSD is expressed in adrenal glands and gonadal tissues, where it catalyzes conversion of pregnenolone, 17-hydroxypregnenolone (17OHPreg) and dehydroepiandrosterone (DHEA) into aldosterone, cortisol and androstenedione respectively. Patient with salt-wasting 3βHSD def need mineralocorticoids, glucocorticoids along with sex steroid replacements. Clinical presentation varies with different degrees of salt wasting, incomplete masculinization in males and virilization in females, depending on the severity of the gene mutation. Elevated 17-OHPreg and its ratio with cortisol along with elevated Δ-5 steroids is used for diagnosis with confirmation through genetic testing, compared with 17-OHP levels which are mainly used for 21-OHD diagnosis. Management is challenging with glucocorticoid and mineralocorticoid replacement therapy with risk of under-/over-replacement, some requiring higher doses compared with other forms of CAH. There is higher risk of long term complication such as obesity, reduced adult height, infertility, osteoporosis, TARTs. Compared with 21-OHD, patients with complete 3βHSD def may need sex steroid replacement at puberty including testosterone (males) and cyclic estrogen-progesterone therapy (females). Timing of hydrocortisone should be individualized as higher doses in the morning or evening showed no substantial differences affecting sleep rating, daily activity score, nocturnal BP. DHEA is a useful marker for the adequacy of the therapy along with clinical monitoring. Presentation: No date and time listed

The influence of estro-progestin therapy on neurohormonal activity in functional hypothalamic amenorrhea

Background: Functional hypothalamic amenorrhea (FHA) is a chronic endocrine disorder caused by the abnormal pulsatile secretion of neurohormones in the hypothalamus. Secretion of GnRH is regulated by kisspeptin/neurokinin B/dynorphin (KNDy) neurons. These neurons produce, among other neurohormones, neurokinin B (NKB) which regulates the coordinated stimulation or inhibition of GnRH secreting neurons. Aim of the study: Assessment and comparison of serum NKB in patients with FHA at baseline, and following 6 months of estrogen-progestagen therapy. Materials and methods: Fifty-five patients with functional hypothalamic amenorrhea were included in the study group. Serum concentrations of neurokinin B (NKB), follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-β-estradiol (E2), prolactin (PRL), cortisol, testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), fasting glucose and insulin, as well as lipid profile were measured at baseline. At the time of diagnosis, patients with FHA were prescribed a course of 2 mg 17-β-estradiol and 10 mg dydrogesterone for duration of 6 months. Serum NKB was then reassessed following treatment at 6 months. Results: At baseline, the FHA group was found to have a decreased serum NKB concentration when compared to a healthy control group. Following 6 months of sequential estrogen-progestogen hormone therapy, this study did not find any statistically significant difference in serum NKB concentration in the treatment arm compared to baseline. Conclusions: For the first time, NKB secretion has been studied in patients with FHA. A significantly lower level of serum NKB was observed in these patients at baseline, when compared to a control group. After 6 months of combination estrogen-progesterone therapy, no significant changes in NKB levels were observed in these patients. These findings, for the first time in the literature, provide insight into the perceived benefit of HRT, calling into question its benefit in addressing the underlying etiopathogenetic contributors of FHA. These new findings may contribute to more targeted and appropriate treatment of such patients in the future.

Adult acampomelic campomelic dysplasia and disorders of sex development due to a reciprocal translocation involving chromosome 17q24.3 upstream of the SOX9 gene

Balanced chromosomal rearrangements with a breakpoint located upstream of the sex determining region Y-box 9 (SOX9) gene on chromosome 17q24.3 are associated with skeletal abnormalities, campomelic dysplasia (CMPD), or acampomelic campomelic dysplasia (ACMPD). We report on a female patient with a reciprocal translocation of t (11; 17) (p15.4; q24.3), who was diagnosed with acampomelic campomelic dysplasia. The 34-year-old Japanese patient presented with distinct skeletal abnormalities, profound intellectual disability, and female phenotype despite the presence of Y chromosome and the sex determining region Y (SRY) gene. Her menarche started at 33 years and 4 months after hormone therapy of estrogen therapy followed by estrogen progesterone therapy. By conducting whole genome sequencing followed by Sanger sequencing validation, we determined the precise breakpoint positions of the reciprocal translocation, one of which was located 203 kb upstream of the SOX9 gene. Considering the phenotypic variations previously reported among the CMPD/ACMPD patients with a chromosomal translocation in the vicinity of SOX9, the identified translocation was concluded to be responsible for all major phenotypes observed in the patient.

The Trend in the Sales of Menopausal Hormone and Other Osteoporosis Medications in South Korea from 2016 to 2019.

BackgroundIncreasing geriatric population, osteoporosis prevalence, and interest in bone health are key contributing factors for the growth of osteoporosis medication markets. Thus, this study evaluated changes in the menopausal hormone and other osteoporosis medication markets from 2016 to 2019.MethodsThis study’s dataset was obtained from the International Marketing Services of IQVIA Inc. in South Korea. The sales of medications for osteoporosis treatment with menopausal hormones were evaluated for drug sales for osteoporosis treatment from 2016 to 2019.ResultsThe results showed that the tissue-selective estrogen complex (TSEC) sales had increased annually while the estrogen-progesterone therapy (EPT) sales had decreased. Excluding menopausal hormones, bisphosphonates were the most widely sold medications for osteoporosis treatment. Among the bisphosphonate medications, sales of ibandronate and zoledronate increased annually, while alendronate and risedronate decreased. Teriparatide also showed increasing sales. A rapid rise was noted in the sales of denosumab.ConclusionsWhile the sales of TSEC, injectable bisphosphonates, and denosumab have increased annually, the sales of EPT, estrogen therapy, oral bisphosphonates have not increased, as reflected in hormone therapy and osteoporosis medication market trends. This study showed the recent trends in hormone therapy and the osteoporosis medication market from 2016 to 2019 in South Korea.

To Be or Not to Be: Pregnant or Not

Background: Beta Human chorionic gonadotropin (β-hCG) is used for diagnosing pregnancy. Differential diagnosis for elevated β-hCG includes false positive test due to antibody interference, gestational trophoblastic disease (GTD), pituitary production of β-hCG or non-gestational malignancies including hepatic, neuroendocrine, breast, ovarian, pancreatic, cervical, and gastric cancers. We are presenting a case of a menopausal woman noted to have persistently positive serum pregnancy test. Case: 42-year-old female (G3 P2 A1) with a history of thyroid nodules and hypothyroidism was referred to endocrinology clinic for persistently positive serum pregnancy test without being pregnant. Last C-section delivery was 13 yrs ago. Last menstrual period was more than one year ago. Prior to that, her menstruation had always been irregular. Patient denied any spotting, pelvic discomfort/pain or weight loss in last few months. Seven months ago, POCT urine UCG test was done as per radiology protocol prior to CT abdomen for flank pain, and came back positive. Serum β-hCG was mildly positive at 4.3 (0.0 - 2.4 mIU/ml). Pelvic ultrasound did not show presence of a gestational sac. Repeat serum β-hCG level a week later was 3.8 mIU/ml. Patient was told she had early miscarriage. However, about 6 months later, PCP repeated serum β-hCG level and was elevated at 6.2 mIU/ml and thus patient was referred to endocrinology. Further work up showed FSH 61.3 (post-menopausal: 13.1-86.5 mIU/ml), prolactin 12.6 (3.0-18.6 ng/mL), TSH 9.41(0.47 - 4.70 uIU/ml) and estradiol level <15 pg/ml. β-hCG by dilution was ordered but was cancelled by lab for unknown reason. Patient was then also seen by OB-GYN who advised patient that she is menopausal and started her on estrogen-progesterone (E/P) therapy. About 4 weeks after starting E/P therapy, urine UCG came back negative. Hyper- glycosylated hCG (H-hCG) was not elevated. Patient was explained that false positive pregnancy test was due to pituitary production of β-hCG. Discussion: We propose considering following aspects when approaching a case of elevated β-hCG in absence of pregnancy. 1) Hook effect can mask very high level of β-hCG, repeating test after dilution will rule out hook effect. 2) Many case studies have shown pituitary production of β-hCG in perimenopausal women. Perimenopausal women 41-55 years of age with mildly elevated serum β-hCG levels (5.0-14.0 mIU/ml) and concomitant FSH level over 45.0 mIU/ml are likely to have pituitary production of β-hCG(1). If we can suppress β-hCG with two weeks of E/P therapy, this supports pituitary production of β-hCG. 3) If above testing is equivocal then one can consider checking H-hCG which is predominately secreted by the more invasive cytotrophoblastic cells, and supports diagnosis of GTD.

Effects of herbal preparations containing isoflavones on bone metabolism in postmenopausal women

The effects of the mixed herbal preparation "Tzuo-Kuai-Wuan" (TKW) on bone metabolism were compared with a single herb containing equivalent amounts of isoflavones, daidzein and genistein, and a combined estrogen-progesterone therapy (EPT). One hundred women completed the trial, 33 in group A, consuming a single herb, 30 in group B, consuming TKW, and 37 in group C, receiving EPT. In both herbal groups, the serum levels of daidzein significantly increased after treatment for 6 months (224% in group A and 234% in group B, both p < 0.01), though the serum levels of genistein did not change significantly. In group C, serum levels of either isoflavone changed only slightly. After 6 months of treatment, the bone formation marker (bone specific alkaline phosphatase [BSAP]) significantly increased in group B, but not in group A (25.4% vs. 15.9%, p < 0.01 and p = 0.09, respectively). The elevation of BSAP was related to increased serum daidzein and genistein (β = 0.498 and 0.248, p < 0.01 and p = 0.03, respectively). The bone resorption marker (urinary deoxypyridinolines/creatinine [Dpd/Cr]) was nearly the same at beginning of the study and after treatment in both herbal groups. In contrast, BSAP and Dpd/Cr significantly decreased after 3 and 6 months of treatment in group C (BSAP: 10.4% and 30.3%; Dpd/Cr: 21.7% and 43.8%, all p < 0.01 in paired t-tests). Thus, we conclude that TKW stimulates bone formation, in contrast to EPT which primarily inhibits resorption. This effect appears to be related to the amount of isoflavones. Further, the stronger effect in women consuming TKW than consuming a single herb that contains equivalent amounts of isoflavones suggests higher synergistic or additive effect of other components than isoflavones in TKW.

Doppler ultrasonography of the ophthalmic artery in perimenopausal and postmenopausal women: a new approach

Background The vascular endothelium has specific estrogen receptors and the impact of hormone therapy (HT) on circulation is associated with cardiovascular protection in perimenopause and postmenopause. Blood vessels can be assessed by ultrasound Doppler velocimetry, and more specifically the study of the ophthalmic artery (OA) can be used for brain vessel assessment; more recently, it is a possible method for cardiovascular risk assessment. Methods A cross-sectional study involved perimenopausal and postmenopausal women divided into three groups: 60 non-HT users (control group), 23 users of estrogen therapy (ET group), and 23 users of estrogen–progesterone therapy (EPT group). Doppler velocimetry of the OA was performed with analysis of the resistance index (RI), pulsatility index (PI), systolic peak velocity (P1), second systolic peak velocity (P2), peak velocity ratio (PVR), final diastolic velocity (FDV), and ratio between means of systolic and diastolic velocity (SDR). Results There was no significant difference between the groups in Doppler velocimetry indices of the OA: RI (p = 0.94), PI (p = 0.85), P1 (p = 0.81), P2 (p = 0.53), PVR (p = 0.41), FDV (p = 0.76), and SDR (p = 0.84). We observed a positive correlation of the SDR with age only in the control group (r = 0.34, p = 0.01). Conclusions There is a positive correlation between the SDR and age in the control group. Therefore, this new index is a promising instrument in the non-invasive assessment of cardiovascular risk.

Assessment of interactions between 205 breast cancer susceptibility loci and 13 established risk factors in relation to breast cancer risk, in the Breast Cancer Association Consortium.

BackgroundPrevious gene-environment interaction studies of breast cancer risk have provided sparse evidence of interactions. Using the largest available dataset to date, we performed a comprehensive assessment of potential effect modification of 205 common susceptibility variants by 13 established breast cancer risk factors, including replication of previously reported interactions.MethodsAnalyses were performed using 28 176 cases and 32 209 controls genotyped with iCOGS array and 44 109 cases and 48 145 controls genotyped using OncoArray from the Breast Cancer Association Consortium (BCAC). Gene-environment interactions were assessed using unconditional logistic regression and likelihood ratio tests for breast cancer risk overall and by estrogen-receptor (ER) status. Bayesian false discovery probability was used to assess the noteworthiness of the meta-analysed array-specific interactions.ResultsNoteworthy evidence of interaction at ≤1% prior probability was observed for three single nucleotide polymorphism (SNP)-risk factor pairs. SNP rs4442975 was associated with a greater reduction of risk of ER-positive breast cancer [odds ratio (OR)int = 0.85 (0.78-0.93), Pint = 2.8 x 10–4] and overall breast cancer [ORint = 0.85 (0.78-0.92), Pint = 7.4 x 10–5) in current users of estrogen-progesterone therapy compared with non-users. This finding was supported by replication using OncoArray data of the previously reported interaction between rs13387042 (r2 = 0.93 with rs4442975) and current estrogen-progesterone therapy for overall disease (Pint = 0.004). The two other interactions suggested stronger associations between SNP rs6596100 and ER-negative breast cancer with increasing parity and younger age at first birth.ConclusionsOverall, our study does not suggest strong effect modification of common breast cancer susceptibility variants by established risk factors.

Primary Ovarian Insufficiency: The Paradox of Menopause in Young Women

Primary ovarian insufficiency (POI) refers to the loss of ovarian function in young women. It can lead to primary or secondary amenorrhea. The loss of ovarian function is usually permanent akin to menopause. Resultant hypoestrogenemia has systemic adverse effects particularly on the bone health. POI is diagnosed on the basis of raised serum follicle stimulating hormones levels. Most of the cases are idiopathic. Hypothyroidism is the most common associated disorder suggesting autoimmune etiology in some of the cases. Karyotypic abnormalities (mostly monosomy X-Turner syndrome) should be excluded in cases presenting with primary amenorrhea or early onset secondary amenorrhea. Treatment involves long-term estrogen-progesterone replacement therapy which provides regular withdrawal bleed and prevents systemic effects of hypoestrogenemia.

Successful pregnancy after conservative management of early stage endometrial carcinoma in a young nulliparous woman.

Successful pregnancy after conservative management of early stage endometrial carcinoma in a young nulliparous woman.

Estrogen Replacement Therapy and Cardiac Function Under Metabolic Syndrome

See related article, pp 694–704 Regardless of age, race, and ethnicity, cardiovascular disease is the number 1 cause of death for women, and its prevalence rises rapidly after menopause.1–4 This postmenopausal increase is believed to result from the loss of endogenous estrogen. Although estrogen replacement therapy (ERT) has long been thought to protect against menopause-associated cardiovascular anomalies, osteoporosis, hot flashes, and thinning of the vaginal epithelium,3–5 findings from the Heart and Estrogen/Progestin Replacement Study and the Women's Health Initiative Study5 do not support the notion that ERT protects the cardiovascular system. Instead, the data indicate just the opposite, that is, increased risk of cardiovascular disease, in addition to the apparent higher risk of breast cancer and deep vein thrombosis.1,2,4 Although results from clinical trials have substantiated the beneficial role of ERT in the management of menopausal symptoms, the unexpected finding of exacerbated cardiovascular function after ERT has made women hesitant to initiate ERT after menopause.1 Further analysis of the clinical trials revealed that the age of a woman and especially the number of years after menopause onset may be primary factors that contribute to the ultimate cardiovascular outcome of ERT. Although estrogen-progesterone therapy was found beneficial in young postmenopausal women, it increased cardiovascular risk when initiated in older postmenopausal women with established coronary artery disease.2,4 It is, thus, recommended that ERT be limited to the shortest duration consistent with treatment goals (eg, relief of menopausal symptoms).1 In contrast to the generalized recommendation for short duration of menopausal hormone treatment,2,4 careful scrutiny of the data from the Women's Health Initiative Estrogen Plus Progestin Trial reveal a reduced coronary heart disease risk after 5 to 6 years of ERT treatment. Accordingly, the …

Effect of Estrogen Receptor β A1730G Polymorphism on ABCA1 Gene Expression Response to Postmenopausal Hormone Replacement Therapy

The estrogen receptor β (ERβ) mediates the action of estrogen on metabolism of lipids and lipoprotein. Therefore, its gene is a promising candidate gene for cardiovascular disease. The aim of the present study was to investigate whether the ERβ A1730G polymorphism modifies the metabolic response to hormone replacement therapy (HRT) in postmenopausal women. The population included 60 normolipidemic postmenopausal women with equal numbers of each A1730G genotype followed during a 90-day experimental period. All subjects received oral estrogen together with a progestin therapy during the HRT. ABCA1 gene expression and serum lipid and lipoprotein concentrations were measured at the beginning and end of the HRT trial. At baseline, ABCA1 gene expression, lipid or lipoprotein concentrations were not significantly different among the ERβ A1730G genotype groups. After HRT, however, subjects with GG genotype had a greater increase in ABCA1 gene expression (p = 0.002) and a trend toward greater increase in apoA-I (p = 0.058) than subjects carrying the A allele. An interaction effect between genotype and HRT effect was observed on ABCA1 gene expression. In conclusion, the positive changes of ABCA1 gene expression and apoA-I were affected by the ERβ A1730G polymorphism in women taking estrogen-progesterone therapy.

The effects of postmenopausal hormone therapy on serum estrogen, progesterone, and sex hormone-binding globulin levels in healthy postmenopausal women

Differences in disease outcomes between users and nonusers of hormone therapy (HT) and between users of estrogen therapy (ET) and users of estrogen + progesterone therapy (EPT) may relate to differences in serum hormone concentrations between these populations. In this study, we examined the response of serum hormone levels in healthy postmenopausal women after 1 year of HT. A representative subsample of 200 healthy adherent participants from the active and placebo groups of the Women's Health Initiative randomized controlled clinical trials of ET (conjugated equine estrogens 0.625 mg daily) or EPT (ET plus medroxyprogesterone acetate 2.5 mg daily) were selected for the determination of selected sex hormone levels at baseline and 1 year after randomization. In participants receiving active ET intervention compared with placebo, estrogenic hormone levels increased from baseline to year 1 by 3.6-fold for total estrone, 2.7-fold for total estradiol, and 1.8-fold for bioavailable and free estradiol concentrations. Serum sex hormone-binding globulin concentrations also increased 2.5-fold. In contrast, progesterone levels decreased slightly in women taking exogenous EPT. The response of serum estrogens and sex hormone-binding globulin did not differ substantially with the addition of progesterone. In subgroup analyses, hormone response varied by age, ethnicity, body mass index, smoking status, vasomotor symptoms, and baseline hormone levels. These data provide a reference point for the serum hormone response to HT and demonstrate that the response of serum estrogens is similar for ET and EPT. The implications of the slight decrease in serum progesterone levels with EPT therapy are uncertain. Potential treatment interactions for estrogenic hormones were identified, which suggest a larger response to HT in women with low endogenous levels.

Hormone therapy and intraocular pressure in nonglaucomatous eyes

The influence of sex hormones on intraocular pressure (IOP) has been the focus of recent debate. Previous studies investigating the effects of hormone therapy (HT) on IOP in postmenopausal women have produced conflicting results but have been limited by small numbers of participants. The aim of our study was to compare IOP in women without glaucoma taking HT with those not taking HT. A prospective cross-sectional study of postmenopausal women visiting a single ophthalmic medical practitioner was conducted. All women with a history of intraocular disease, a family history of glaucoma, or refractive error exceeding +/-5 diopters were excluded. Applanation tonometry was used to measure IOP, and participants were then asked if they were current HT users. A total of 263 participants were recruited, of whom 91 reported current use of HT; 172 had never used HT. Within the HT group, 33 were taking an estrogen-therapy and 58 were taking a estrogen-progesterone therapy. Mean IOP in the HT group was significantly lower than that in the non-HT group; the mean difference was 1.41 mm Hg (P < 0.001). This difference remained statistically significant after statistical correction for age, use of systemic beta-blockers, and time of IOP measurement. There was no significant difference in mean IOP between women taking combined versus those taking estrogen-only preparations. Our study showed that IOP was significantly lower in women taking HT than in those who had never taken HT, even after removing other possible influences on IOP. The IOP-lowering effect of HT deserves further investigation to explore whether it may represent a possible new therapeutic modality for glaucoma.