Estrogen deficiency is the one of pathogenetic causes of postmenopausal osteoporosis. Exogenous estrogen may prevent postmenopausal bone loss, so to prevent postmenopausal osteoporosis and osteoporotic fracture. The effect of estrogen on postmenopausal syndrome can not be substituted with other medicine. However, the attention should be paid to the safety of hormone replacement therapy (HRT) during its long term use, and HRT should be used individually.
Aged ; Drug Therapy, Combination ; Estrogen Replacement Therapy ; Estrogens, Conjugated (USP) ; administration & dosage ; Female ; Humans ; Medroxyprogesterone ; administration & dosage ; Middle Aged ; Osteoporosis, Postmenopausal ; prevention & control ; Progesterone Congeners ; administration & dosage

In female sexual dysfunction (FSD), psychological and contextual factors significantly influence organic components of sexual response and behavior. The hormonal environment also affects FSD. Therefore, a tailored medical approach to each individual's sexual symptom is inevitable. This paper reviews currently available pharmacological treatment of FSD including the most recent advances and future targets in pharmacotherapy. In hormonal therapies for FSD, efficacy of estrogens and androgens on the treatment of vaginal atrophy, low sexual desire, and small subsets of genital arousal disorder, respectively, have been demonstrated. However, we need more data regarding long-term safety. There are two non-hormonal agents approved by the US Food and Drug Administration. Flibanserin has shown marginal benefit over placebo for the treatment of hypoactive sexual desire disorder. Ospemifen has shown beneficial effect on vulvovaginal pain from hormone related atrophy although it requires a longer period data to assess safety in other female genital organs, such as uterus and ovaries. Controversies still remain regarding hormonal therapies for FSD. Besides, some of the developing drugs still require more reliable safety and efficacy data. However, pharmacologic treatment of FSD is a promising field yet to be explored.
Androgens ; Arousal ; Atrophy ; Drug Therapy ; Estrogens ; Female* ; Genitalia, Female ; Humans ; Ovary ; Sexual Dysfunctions, Psychological ; United States Food and Drug Administration ; Uterus

OBJECTIVETo establish an appropriate animal model of uterine leiomyoma and to understand the pathogenesis of this disease.

METHODSMature female rats were intramuscularly injected with estradiol benzoate at 200 μg or 300 μg twice a week. After injection for 8 or 10 weeks, the rats were sacrificed. We measured the serum levels of estrogen (E(2)) and progesterone (P), evaluated ER and PR expression, and calculated the leiomyoma forming rate and mortality of the rats. Histological changes were compared between rat uterine leiomyoma and human uterine leiomyoma with HE staining. The optimal dose and duration of E(2) for induction of uterine leiomyoma in rat were determined.

RESULTSIn the rats treated with estradiol benzoate 200 μg for 8 weeks ìn the serum E(2) level increased significantly (P<0.01). Uterine nodules were visible in some of the tested rats. Based on the pathohistological Results , the uterine leiomyoma developed in the treated rats demonstrated similar features as in human uterine leiomyoma. The expressions of ER and PR were increased in the leiomyoma tissues.

CONCLUSIONThe rat model of uterine leiomyoma can be established by intramuscular injection of estradiol benzoate at 200 μg twice per week for 8 weeks, with similar features as those of human uterine leiomyoma. The high concentrations of ER and PR in uterine tissue might be related with the development of uterine leiomyoma in animal.

Animals ; Disease Models, Animal ; Estrogens ; administration & dosage ; adverse effects ; Female ; Leiomyoma ; chemically induced ; Rats ; Uterine Neoplasms ; chemically induced

Telomeres undergo attrition with each cell division, and telomere length is associated with age-related diseases and mortality in the elderly. Estrogen can influence the attrition of telomeres by diverse mechanisms. This is a retrospective case control study that investigated the influence of long-term hormone therapy (HT) on telomere length in postmenopausal women. We recruited 130 postmenopausal women from 55 to 69 years of age for this study, and divided them into two groups. The first group included 65 women who had been on estrogen and progesterone therapy for more than five years (HT group). The other group was composed of 65 women matched in age to the HT group who had never had HT (non- HT group). The relative ratios of telomere length of study subjects to a reference DNA from a healthy young female were measured using quantitative PCR. Plasma levels of lipid profiles, total antioxidant status (TAS), C-reactive proteins (CRP), fasting glucose levels, and estradiol levels were measured. Age at menopause, vitamin use, and exercise, alcohol, and cigarette smoking histories were also assessed in a questionnaire. Mean duration (+/- SD) of HT was 8.4 +/- 2.3 years. Prevalence of vitamin use and regular exercise were higher in the HT group than in the non-HT group (p < 0.01). Relative telomere length ratios in the HT group were significantly greater than those in the non-HT group (p < 0.01). HT was significantly correlated with the relative telomere length ratio in multivariate analysis when potential confounding variables were controlled for (p < 0.05). In conclusion, telomere lengths were longer in postmenopausal women who had a history of long-term HT than in postmenopausal women without HT. Long-term HT in postmenopausal women may alleviate telomere attrition.
Aged ; DNA Damage ; Estrogens/*administration & dosage ; Female ; *Hormone Replacement Therapy ; Humans ; Middle Aged ; Postmenopause ; Progesterone/*administration & dosage ; Research Support, Non-U.S. Gov't ; Telomere/*drug effects ; Time Factors

OBJECTIVETo observe the effects of long-term and low-dose hormone replacement therapy on bone mineral density (BMD), and the incidence of bone pain in postmenopausal women.

METHODSTotally 141 postmenopausal women were selected from the medical staff of the Peking Union Medical College Hospital. Of them, 63 women treated with low-dose sex hormone for over 5 (5-32) years were divided into hormone replacement therapy (HRT) group, and 78 never receiving HRT were divided into control group. The BMD was measured by dual energy X-ray absorptiometry (DEXA) at lumbar spine, Ward's triangle, femoral neck, trochanter, and total hip, and the incidence of bone pain was inquired.

RESULTSThe BMD in the HRT group was 9.1% higher than that in the control group (P < 0.05). The incidence of bone pain was significantly lower in the HRT group (71.4%) than that in the control group (89.7%).

CONCLUSIONLong-term and low-dose hormone replacement therapy can reduce bone loss and the incidence of bone pain.

Absorptiometry, Photon ; Bone Density ; Estrogens ; administration & dosage ; Female ; Hormone Replacement Therapy ; Humans ; Middle Aged ; Osteoporosis, Postmenopausal ; prevention & control ; Progesterone ; administration & dosage

OBJECTIVETo compare profiles and related factors of irregular bleeding induced by different types of low-dose hormone therapy (HT) and a Chinese formulated herbs products.

METHODSApplied with open-labeled, randomized, and clinical trial design, 136 postmenopausal women were assigned into four groups: group A: estradiol valerate (E2 V) 1 mg/d + medroxyprogesterone acetate (MPA) 2 mg/d; group B: conjugated equine estrogen 0.45 mg/d + MPA 2 mg/d; group C: tibolone 1.25 mg/d; group D: a Chinese formulated herbs product (Kuntai) 4# tid. Each subject took element calcium 400 mg/d and vitamin D 200 IU/d concomitantly. Modified Kupperman scores were assessed on baseline and every 3 months thereafter and irregular bleeding was recorded on menopausal diary every day. The duration of this study was 1 year. Results The efficacies were similar in three HT-managed groups, but was better than in group D, although the latter was also effective in alleviating menopausal symptoms. Hazard ratio (HR) of irregular bleeding was 1.00 in group C, 2.43 in group A (95% CI: 1.08-5.46), 3.12 in group B (95% CI: 1.42-6.88), and 0.73 in group D (95% CI: 0.26-2.04). Most cases initially experienced bleeding in the first 3 months but such initiation was a bit later in group C. Endometrium, as detected by B-mode ultrasound, increased approximately 1 mm in HT groups, while it was a bit thicker in group C. Long periods in reproductive age and short time since menopause were high risk factors for irregular bleeding.

CONCLUSIONProfiles of irregular bleeding in 3 commonly used types of low-dose HT are different and some factors such as long period in reproductive age and short time since menopause may contribute to bleeding initiation.

Adult ; Aged ; Double-Blind Method ; Estradiol ; administration & dosage ; analogs & derivatives ; Estrogen Replacement Therapy ; adverse effects ; Estrogens, Conjugated (USP) ; administration & dosage ; Female ; Humans ; Medroxyprogesterone Acetate ; administration & dosage ; Metrorrhagia ; etiology ; Middle Aged ; Norpregnenes ; administration & dosage ; Phytotherapy ; adverse effects ; Postmenopause ; Risk Assessment

OBJECTIVES: This study was conducted to examine the effects of hormone therapy on serum lipid levels in postmenopausal Korean women. METHODS: This retrospective cohort study included 154 healthy postmenopausal Korean women. Seventy-nine women took oral estrogen (conjugated equine estrogen 0.625 mg/day or equivalent), and 75 applied estrogen transdermally using 0.1% 17beta-estradiol gel. Micronized progesterone (MP) was added to 40 women of oral group and 49 women in transdermal group. Serum levels of triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and lipoprotein (a) were measured before, 3 and 6 month after hormone therapy. RESULTS: At baseline, mean body mass index (BMI) were lower (22.76 vs. 23.74 kg/m2) and proportion of family history of cardiovascular disease (CVD) (61 vs. 39%) were higher in oral group. In oral group, LDL-C and lipoprotein(a) levels decreased, and triglyceride and HDL-C levels increased significantly after 3 and 6 months. There was no significant change in lipoprotein levels compared to the baseline in transdermal group. There were also no differences with additional MP. Changing pattern of HDL-C during 6 months was significantly different by the route of estrogen administration. CONCLUSION: Oral estrogen therapy might be more beneficial than transdermal estrogen in terms of lipid in postmenopausal Korean women. The estrogen effects are not influenced by adding MP.
Body Mass Index ; Cardiovascular Diseases ; Cholesterol ; Cohort Studies ; Drug Administration Routes ; Estrogens ; Female ; Hormone Replacement Therapy ; Humans ; Lipoprotein(a) ; Lipoproteins ; Progesterone ; Retrospective Studies ; Triglycerides

PURPOSE: Ginseng is a traditional Asian remedy for sexual dysfunction. The purposes of this study were to investigate the effects of Korean red ginseng (KRG) on the vaginal blood flow and tissue structure in female castrated rats. MATERIALS AND METHODS: Female Spague-Dawley rats (200-210gm) were divided into 4 groups: the control (n=20), castration (n=30), and castration plus oral administration of KRG extracts (50 and 100mg/kg/day, n=15 and n=15, respectively). After 1 month of treatment, the serum estrogen and total cholesterol levels were measured. The vaginal blood flow was measured using laser Doppler flowmeter before and after pelvic nerve stimulation (PNS). The vaginal tissue was processed for Masson's trichrome stain, immunohistochemistry and Western blotting. RESULTS: The serum estrogen level was significantly decreased in the castration group (0.8+/-1.9ng/ml); however, it increased up to the control level (2.2+/-1.3ng/ml) in both the KRG administration groups (p<0.05). The PNS-induced vaginal blood flow tended to improve in the KRG treatment groups. On the histology, the vaginal epithelial layer and submucosal microvasculature showed improvement in the KRG treatment groups. The expression of estrogen receptor increased in the KRG treatment groups compared to the castration group. CONCLUSIONS: These results suggested that KRG extracts seem to have an estrogenic effect on castrated female rats. This implies that the KRG extracts may have an ameliorating effect on sexual function in menopausal woman.
Administration, Oral ; Animals ; Asian Continental Ancestry Group ; Blotting, Western ; Castration ; Cholesterol ; Estrogens ; Female* ; Flowmeters ; Humans ; Immunohistochemistry ; Menopause ; Microvessels ; Panax* ; Rats* ; Vagina

OBJECTIVETo investigate the effects of high-dose estrogen on the development of the prostate in new-born SD rats and its possible relationship with the sonic hedgehog (SHH) signaling pathway.

METHODSOne hundred new-born male SD rat pups were assigned to an experimental group, subcutaneously injected with 25 microg Estradiol + 25 microl corn oil vehicle, and a control group, given corn oil alone, on postnatal day (PD) 0, 1, 3 and 5. The animals were sacrificed by decapitation and their prostates removed on PD 1, 6, 10, 20 and 30. The morphological changes of the prostate were observed by HE staining, and SHH signaling related molecules were detected by immunohistochemistry and reverse transcription PCR.

RESULTSHigh-dose estrogen significantly inhibited the organogenesis of the new-born SD rat prostate and down-regulated the expressions of SHH signaling related molecules.

CONCLUSIONHigh-dose estrogen may restrain the development of the prostate in new-born SD rats via inhibition of SHH signaling.

Animals ; Animals, Newborn ; Estrogens ; administration & dosage ; pharmacology ; Hedgehog Proteins ; metabolism ; Male ; Prostate ; drug effects ; growth & development ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects

Ospemifene—a third-generation selective estrogen receptor modulator approved by the Food and Drug Administration in 2013—is an oral medication for the treatment of dyspareunia. In postmenopausal women with vulvovaginal atrophy, ospemifene significantly improves the structure and pH levels of the vagina, reducing dyspareunia. It is available as a 60-mg tablet; hence, women who may have had prior difficulty with vaginal administration or on-demand use of nonprescription lubricants and moisturizers would likely prefer this form of treatment. Preclinical studies demonstrated that ospemifene has an estrogen agonist action on the bone, reducing the cell proliferation of ductal carcinoma in an in situ model. Studies evaluating the safety of treatment for up to 52 weeks have shown that ospemifene is a safe medication with minimal impact on the endometrium. Further studies with larger number of subjects are necessary to better conclude its effects and long-term safety.
Administration, Intravaginal ; Atrophy* ; Carcinoma, Ductal ; Cell Proliferation ; Dyspareunia ; Endometrium ; Estrogens ; Female ; Humans ; Hydrogen-Ion Concentration ; Lubricants ; Menopause ; Selective Estrogen Receptor Modulators ; Tamoxifen ; United States Food and Drug Administration ; Vagina ; Vulva