Takahashi, K., Manabe, A., Okada, M., Kurioka, H., Kanasaki, H., & Miyazaki, K. (2000). Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas, 34(2), 169-177. https://doi.org/10.1016/s0378-5122(99)00108-5
Takahashi K, Manabe A, Okada M, Kurioka H, Kanasaki H, Miyazaki K. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas. 2000;34(2):169-177. doi:10.1016/s0378-5122(99)00108-5
Takahashi, Kentaro, et al. "Efficacy and safety of oral estriol for managing postmenopausal symptoms." Maturitas, vol. 34, no. 2, 2000, pp. 169-177.
For EndNote, Zotero or Mendeley:
License
No open license is recorded for this paper. Reuse terms are set by the publisher.
to assess the therapeutic efficacy and safety of oral estriol for the treatment of climacteric symptoms in postmenopausal women.
Methods
68 postmenopausal women with climacteric symptoms received oral estriol, 2 mg/day, daily for 12 months. We evaluated the degree of climacteric complaints with estriol therapy; serum levels of gonadotropins, estradiol (E2) and lipids; biochemical markers of bone metabolism; blood pressure; and side effects both at baseline and during treatment. Climacteric symptoms were assessed according to the menopausal index (MI), a version of the Kupperman index that had been modified for Japanese women.
Results
oral estriol therapy significantly reduced total MI scores. The greatest relief was noted for hot flushes, night sweats, and insomnia. Estriol treatment significantly lowered serum follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentrations but did not affect any of the other parameters (lipids, bone, liver and blood pressure) during the study period. Slightly vaginal bleeding occurred in 14.3% of those who underwent natural menopausal women. Histologic evaluation of the endometrium and ultrasound assessment of the breasts following 12 months of estriol treatment found normal results in all women.
Conclusion
Estriol is a safe and effective alternative for relieving climacteric symptoms in postmenopausal Japanese women.
Bulun SE et al., 2019·Endocr Rev·Free full text on PubMed Central
Pelvic endometriosis is a complex syndrome characterized by an estrogen-dependent chronic inflammatory process that affects primarily pelvic tissues, including the ovaries. It is caused when shed endometrial tissue travels retrograde into the lower abdominal cavity. Endometriosis is the most common cause of chronic pelvic pain in women and is associated with infertility. The underlying pathologic mechanisms in the intracavitary endometrium and extrauterine endometriotic tissue involve defectively programmed endometrial mesenchymal progenitor/stem cells. Although endometriotic stromal cells, which compose the bulk of endometriotic lesions, do not carry somatic mutations, they demonstrate specific epigenetic abnormalities that alter expression of key transcription factors. For example, GATA-binding factor-6 overexpression transforms an endometrial stromal cell to an endometriotic phenotype, and steroidogenic factor-1 overexpression causes excessive production of estrogen, which drives inflammation via pathologically high levels of estrogen receptor-β. Progesterone receptor deficiency causes progesterone resistance. Populations of endometrial and endometriotic epithelial cells also harbor multiple cancer driver mutations, such as KRAS, which may be associated with the establishment of pelvic endometriosis or ovarian cancer. It is not known how interactions between epigenomically defective stromal cells and the mutated genes in epithelial cells contribute to the pathogenesis of endometriosis. Endometriosis-associated pelvic pain is managed by suppression of ovulatory menses and estrogen production, cyclooxygenase inhibitors, and surgical removal of pelvic lesions, and in vitro fertilization is frequently used to overcome infertility. Although novel targeted treatments are becoming available, as endometriosis pathophysiology is better understood, preventive approaches such as long-term ovulation suppression may play a critical role in the future.
Takebayashi A et al., 2014·PLoS One·Free full text on PubMed Central
To evaluate the association between endometriosis and chronic endometritis. Endometrial specimens were obtained from 71 patients, 34 with endometriosis (endometriosis group) and 37 without endometriosis (non-endometriosis group), who underwent hysterectomy, and the specimens were immunostained for the plasmacyte marker CD138. The rate of chronic endometritis was compared between the endometriosis group and the non-endometriosis group. Furthermore, the 71 patients were also divided into two groups, 28 with chronic endometritis (chronic endometritis group) and 43 without chronic endometritis (non-chronic endometritis group). Logistic regression analysis was performed with variables including age, body mass index (BMI), gravidity and parity, and diagnoses of leiomyoma, adenomyosis, and endometriosis on pathology to examine the independent effect of each variable on chronic endometritis. Patients suffering from cervical invasive carcinoma, endometrial carcinoma, and endometrial polyps or treated with gonadotropin-releasing hormone agonists, progestins, or oral contraceptives before surgery were excluded. Chronic endometritis was identified in 52.94% of the endometriosis group and 27.02% of the non-endometriosis group (p<0.05). Logistic regression analysis revealed that endometriosis was associated with chronic endometritis. This result suggests a strong association between endometriosis and chronic endometritis.
MacLennan A et al., 2001·Climacteric : the journal of the International Menopause Society
To examine the effectiveness of oral hormone replacement therapy (HRT) with regard to hot flushes and night sweats, which are vasomotor symptoms commonly experienced by menopausal women. Double-blind, randomized, placebo-controlled trials of oral HRT for at least 3 months' duration and reporting vasomotor outcomes were identified using a search strategy developed by the Menstrual Disorders Group and Subfertility Group of the Cochrane Collaboration. Twenty-one trials meeting the selection criteria were included in the review. Study participants totalled 2511. Trial duration ranged from 3 months to 3 years. There was a significant reduction in the weekly hot flush frequency for HRT compared with placebo (weighted mean difference -17.46, 95% confidence interval (CI) -24.72 to -10.21). This was equivalent to a 77% reduction in frequency (95% CI 58.2-87.5) for HRT relative to placebo. Symptom severity was also significantly reduced compared with placebo (odds ratio (OR) 0.13, 95% CI 0.08-0.22). Withdrawal for lack of efficacy occurred significantly more often with placebo therapy (OR 17.25, 95% CI 8.23-36.15). Withdrawal for adverse events, commonly breast tenderness, edema, joint pain and psychological symptoms, was not significantly increased for HRT (OR 1.38, 95% CI 0.87-2.21). In women who were randomized to placebo treatment, a 50.8% (95% CI 41.7-58.5) reduction in hot flushes was observed between baseline and the end of the study. Oral HRT is highly effective in alleviating hot flushes and night sweats. Owing to the marked effect seen with placebo treatment, it is important to compare therapies purported to alleviate vasomotor symptoms with a placebo or an established therapy.
Rozmus-Warcholińska W et al., 2004·Wiadomosci lekarskie (Warsaw, Poland : 1960)
About 30% of female population in Poland is already in the perimenopausal age. The North American Menopausal Society has defined the menopause as the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. Perimenopausal period is often connected with vasomotor symptoms in women. In recent years, there has been a growing recognition among clinicians of the importance of learning more about how patients cope with the symptoms of their condition. The aim of the study was to evaluate the effect of hormone replacement therapy on vasomotor symptoms in perimenopausal women with the use of Kupperman Index. In a six-month (6 treatment periods, 28 days each) randomized study, 75 healthy postmenopausal women were assigned to receive 50 micrograms/day of continuous transdermal estradiol with sequential transdermal norethisterone acetate (NETA) in daily doses of 170 micrograms in a single transdermal patch. The average number of vasomotor symptoms per day measured with Kupperman Menopausal Index decreased from prestudy by over 90%. The substantial improvement in vasomotor symptoms assessed across time was apparent by week 12 of the treatment.
Rotem C et al., 2007·Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology
To determine the efficacy and safety of the herbal formula Phyto-Female Complex (SupHerb, Netanya, Israel; ingredients: standardized extracts of black cohosh, dong quai, milk thistle, red clover, American ginseng, chaste-tree berry) for the relief of menopausal symptoms. A randomized, double-blind, placebo-controlled trial in 50 healthy pre and postmenopausal women, aged 44-65 years, to whom oral Phyto-Female Complex or matched placebo was prescribed twice daily for 3 months. A structured questionnaire on the frequency and intensity of menopausal symptoms was administered weekly from one week before throughout the 3-month treatment period, followed by biochemical tests, breast check, and transvaginal ultrasonography. The women receiving Phyto-Female Complex reported a significantly superior mean reduction in menopausal symptoms than the placebo group. The effect of treatment improvements in menopausal symptoms increased over time; by 3 months there was a 73% decrease in hot flushes and a 69% reduction of night sweats, accompanied by a decrease in their intensity and a significant benefit in terms of sleep quality. Hot flushes ceased completely in 47% of women in the study group compared with only 19% in the placebo group. There were no changes in findings on vaginal ultrasonography or levels of relevant hormones (estradiol, follicle-stimulating hormone), liver enzymes or thyroid-stimulating hormone in either group. Phyto-Female Complex is safe and effective for the relief of hot flushes and sleep disturbances in pre- and postmenopausal women, at least for 3 months' use.
This review's purpose is to highlight evidence that oral micronized progesterone (progesterone) is effective for hot flushes and night sweats (vasomotor symptoms, VMS), improves sleep and is likely safe in menopausal women (who are more than 1 year since last menstruation). Methods include randomized controlled clinical trials (RCT) supplemented with basic science, population and observational data as needed. The barrier to use of progesterone is lack of awareness that safety concerns with estrogen-including 'menopausal hormone therapy' (MHT) are not applicable to progesterone. In a single 3-month RCT, progesterone (300 mg at bedtime) was effective treatment of VMS in 133 healthy menopausal women. It caused an overall 55% VMS decrease, no withdrawal-related VMS rebound and a greater VMS decrease in 46 women with ≥50 moderate-intense VMS/week. Progesterone is equally or more effective than estradiol in improving cardiovascular endothelial function and caused no cardiovascular safety concerns in a 3-month RCT. An 8-year prospective cohort study (E3N) in more than 80 000 menopausal women showed progesterone prevented breast cancer in estrogen-treated women. Multiple RCTs confirm that progesterone (300 mg daily at bedtime) does not cause depression and improves deep sleep. In conclusion, progesterone effectively treats VMS, improves sleep and may be the only therapy that symptomatic women, who are menopausal at a normal age and without osteoporosis, need.
PMID 10714912 10714912 DOI 10.1016/s0378-5122(99)00108-5 10.1016/s0378-5122(99)00108-5 Takahashi et al. 2000, Takahashi 2000
Cite this article
Takahashi, K., Manabe, A., Okada, M., Kurioka, H., Kanasaki, H., & Miyazaki, K. (2000). Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas, 34(2), 169-177. https://doi.org/10.1016/s0378-5122(99)00108-5
Takahashi K, Manabe A, Okada M, Kurioka H, Kanasaki H, Miyazaki K. Efficacy and safety of oral estriol for managing postmenopausal symptoms. Maturitas. 2000;34(2):169-177. doi:10.1016/s0378-5122(99)00108-5
Takahashi, Kentaro, et al. "Efficacy and safety of oral estriol for managing postmenopausal symptoms." Maturitas, vol. 34, no. 2, 2000, pp. 169-177.
