Traditional Chinese herbal medicine in treating amenorrhea caused by antipsychotic drugs: Meta-analysis and systematic review.

ETHNOPHARMACOLOGICAL RELEVANCE: Amenorrhea caused by antipsychotic drugs is not uncommon in clinical practice, and various treatment strategies are used to treat the condition. Chinese herbal medicine has its own theory for amenorrhea caused by antipsychotic drugs and has developed its own medication methods. AIM OF THE STUDY: To review and conduct meta-analysis of the use of traditional Chinese herbal medicine in treatment of amenorrhea caused by antipsychotic drugs. MATERIALS AND METHODS: A search was conducted across seven Chinese electronic databases (the China National Knowledge Infrastructure (CNKI) database, the China Science and Technology Journal Database, the Wanfang Database, the SinoMed, the Foreign Medical Literature Retrieval Service(FMRS), the Chinese University of Hong Kong Library, the Airiti Library), and the following English databases: MEDLINE, PreMEDLINE, OLD MEDLINE、Publisher Supplied Citation in pubmed; JBI EBP Database, EBM Reviews, Embase, OVID Emcare, Ovid MEDLINE(R), Maternity & Infant Care Database(MIDIRS), APA PsycInfo in OVID, and Cochrane Database of Systematic Reviews (Cochrane Reviews), Database of Abstracts of Reviews of Effects (Other Reviews), Cochrane Central Register of Controlled Trials (Clinical Trials),The Cochrane Methodology Register (Method Studies), Health Technology Assessment Database (Technology Assessments), NHS Economic Evaluation Database (Economic Evaluations) in Cochrane Library; and four databases (Science Direct, ProQuest, Web of Science, and Scopus) in official website using common standards and inclusion/exclusion criteria. The remaining reports were used for preliminary studies. Due to inconsistencies in control groups, randomized controlled trials and articles that combined with other drugs were also excluded. This study is a META analysis of a single rate. RESULTS: Initial screening returned 912 potentially relevant publications in all databases. After subsequent filtering, a total of 18 articles were included in the analysis. The overall effectiveness for treatment amenorrhea caused by antipsychotic drugs using traditional Chinese herbal medicine was 0.91, with 95% confidence interval of 0.89-0.93. Notably in most studies, the time needed to achieve this level of effectiveness was relatively long, usually in excess of three months. Although a satisfactory verification of an improvement in menstrual cycling takes time, the long treatment duration is a downside. Our analysis revealed that the following Chinese herbal remedies were most common: Danggui (Angelica sinensis (Oliv.) Diels), Chuanxiong (Ligusticum striatum DC.), Taoren (Prunus persica (L.) Batsch), Honghua (Carthamus tinctorius L.), Gancao (Glycyrrhiza uralensis Fisch.), Fuling ((Fungus) Poria cocos (Schw.) Wolf), Baizhu (Atractylodes macrocephala Koidz.), Xiangfu (Cyperus rotundus L.), Chaihu (Bupleurum chinense DC.), Shudihuang (Rehmannia glutinosa (Gaertn.) DC.(Processed), Baishao (Cynanchum otophyllum C.K.Schneid.) CONCLUSIONS: Chinese herbal medicine can effectively treat amenorrhea caused by psychiatric drugs, although it takes a long time to achieve satisfactory effectiveness. More research is needed to better understand different aspects of Chinese herbal medicine use in treatment of this particular medical condition.

Real-world anticancer medications for reproductive-age women with breast cancer by using a claims database in Japan.

Aim: To describe real-world breast cancer medications among reproductive-age women. Patients & methods: Using data from a Japanese claims database, anticancer prescriptions were classified into seven categories of amenorrhea risk based on fertility preservation guidelines. Results: We identified 2999 women with records of breast cancer and anticancer prescription from 2005 to 2018. The proportions of prescriptions were as follows: high, 4.1-12.9%; intermediate: 6.0-16.3%; low: 0.4-2.3%; very low/no: 0.3-12.2%; unknown: 33.9-45.5%; unlisted combination: 12.2-23.4%; and unlisted drug: 12.5-26.7%. The common drugs in the unknown category were trastuzumab (n = 1527), docetaxel (n = 1014), and paclitaxel (n = 995). For medications unlisted in the guidelines, various drugs and drug combinations were observed. Conclusion: Numerous anticancer drugs are currently being prescribed with insufficient evidence regarding amenorrhea risk.

Lay abstract The ability to have children for breast cancer patients is one of the key issues of cancer survivorship, especially because recent progress in anticancer treatments has enabled patients to achieve longer survival. The fertility preservation guidelines of the American Society of Clinical Oncology (2006) introduce some anticancer treatments that carry potential risks to future fertility. In this study, the anticancer prescriptions of 2999 patients with breast cancer aged between 15 and 49 years were examined. Results showed that several medications are prescribed despite the lack of information on the risk of infertility. This suggests that further research is required to fill the evidence gap, and that decision aid through adequate counseling should be undertaken.

Long-Acting Reversible Contraception: Specific Issues for Adolescents.

Long-acting reversible contraceptives are the most effective methods to prevent pregnancy and also offer noncontraceptive benefits such as reducing menstrual blood flow and dysmenorrhea. The safety and efficacy of long-acting reversible contraception are well established for adolescents, but the rate of use remains low for this population. The pediatrician can play a key role in increasing access to long-acting reversible contraception for adolescents by providing accurate patient-centered contraception counseling and by understanding and addressing the barriers to use.

No. 313-Menstrual Suppression in Special Circumstances.

OBJECTIVE: To provide a Canadian consensus document for health care providers with recommendations for menstrual suppression in patients with physical and/or cognitive challenges or those who are undergoing cancer treatment in whom menstruation may have a deleterious effect on their health. OPTIONS: This document reviews the options available for menstrual suppression, its specific indications, contraindications, and side effects, both immediate and long-term, and the investigations and monitoring necessary throughout suppression. OUTCOMES: Clinicians will be better informed about the options and indications for menstrual suppression in patients with cognitive and/or physical disabilities and patients undergoing chemotherapy, radiation, or other treatments for cancer. EVIDENCE: Published literature was retrieved through searches of Medline, EMBASE, OVID, and the Cochrane Library using appropriate controlled vocabulary and key words (heavy menstrual bleeding, menstrual suppression, chemotherapy/radiation, cognitive disability, physical disability, learning disability). Results were restricted to systematic reviews, randomized controlled trials, observation studies, and pilot studies. There were no language or date restrictions. Searches were updated on a regular basis and new material was incorporated into the guideline until September 2013. Grey (unpublished) literature was identified through searching websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES: The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS: There is a need for specific guidelines on menstrual suppression in at-risk populations for health care providers.

Assessment of ovarian function after chemotherapy in women with early and locally advanced breast cancer from Serbia.

PURPOSE: Among harmful effects of chemotherapy is the reduction of ovarian function. The aim was to determine the serum levels of FSH, LH, estradiol and AMH after chemotherapy followed by endocrine therapy in breast cancer patients. METHODS: The study included 40 premenopausal hormone receptor-positive breast cancer patients aged 33-50 years. Anthracycline-based chemotherapy received 14/40 while anthracycline-taxane combination received 26/40 of patients, followed by tamoxifen (30/40) or tamoxifen plus goserelin (10/40). All of them experienced chemotherapy-induced secondary amenorrhea. Hormone levels were determined by ELISA. Statistics included Spearman's test, Mann-Whitney test and multiple linear regression analysis. RESULTS: Undetectable AMH levels were observed in 62.5 and 33.3% of patients with time period < 2 and ≥ 2 years from completion of chemotherapy to sample collection. Median levels of hormones for patients treated with anthracycline-based compared to anthracycline-taxane therapy were: 15.5 vs. 22.3 IU/L for FSH; 10.9 vs. 13.6 IU/L for LH; 55.5 vs. 39.5 pg/mL for estradiol; 0.11 vs. 0.11 ng/mL for AMH. The multiple linear regression showed that: women who received goserelin had significantly lower FSH; those with shorter time from completion of chemotherapy to sample collection had significantly higher LH and lower estradiol; younger women had higher AMH levels. CONCLUSIONS: The ovarian function was recovered from chemotherapy-induced secondary amenorrhea with time elapsed since the completion of adjuvant chemotherapy. It may be less disrupted in patients who received anthracycline-based chemotherapy and goserelin plus tamoxifen, as well.

Ovarian reserve in breast cancer: assessment with anti-Müllerian hormone.

Anti-Müllerian hormone (AMH) levels fall during chemotherapy. Treatment-induced amenorrhoea is a reversible phenomenon, but few data are available on long-term AMH changes in breast cancer. The aim of the study was to describe serum AMH levels before, during and in the long term after chemotherapy, and to show a potential AMH recovery. Between May 2010 and June 2011, we selected 134 women aged 18-43 years at the time of breast cancer diagnosis who received chemotherapy between 2005 and 2011, and had not undergone an oophorectomy or had previous cytotoxic treatment. The AMH levels were assessed before, during and 4 months to 5.5 years after the end of chemotherapy. During chemotherapy, AMH was undetectable in 69% of women. After chemotherapy, a significant increase in AMH was found, with an average magnitude of +1.2% per month (95% credibility interval: 0.7 to 1.6). Older age and 12 months of amenorrhoea were found to be associated with a lower AMH recovery rate, whereas baseline AMH and number of chemotherapy cycles were not. The process of AMH changes during and after chemotherapy is dynamic, and shows recovery after ovarian injury. Caution should be exercised in interpreting individual AMH assessment in this context.

Menstrual history and quality-of-life outcomes in women with node-positive breast cancer treated with adjuvant therapy on the NSABP B-30 trial.

PURPOSE: Premenopausal women with breast cancer receiving adjuvant chemotherapy are at risk for amenorrhea. The National Surgical Adjuvant Breast and Bowel Project B-30 trial included menstrual history (MH) and quality-of-life (QOL) studies to compare treatments on these outcomes. PATIENTS AND METHODS: Patients were randomly assigned to sequential doxorubicin (A) and cyclophosphamide (C) followed by docetaxel (T; AC→T), concurrent TAC, or AT, which varied in duration (24, 12, 12 weeks, respectively), and use of C. Endocrine therapy was prescribed for women with hormone receptor-positive tumors. MH and QOL were assessed with standardized questionnaires at baseline; cycle 4, day 1; and every 6 months through 24 months. Prespecified analyses examined rates of amenorrhea by treatment arm, the relationship between amenorrhea and QOL, and QOL by treatment arm. RESULTS: Amenorrhea 12 months after random assignment was significantly different between treatment groups: 69.8% for AC→T, 57.7% for TAC, and 37.9% for AT (P < .001). The AT group without tamoxifen had the lowest rate of amenorrhea. QOL was poorer for patients receiving AC→T at 6 months but similar to others by 12 months. Post-treatment symptoms were increased above baseline for all treatments. Multivariable repeated measures modeling demonstrated that treatment arm, time point, age, and tamoxifen use were significantly associated with symptom severity (all P values < .002). CONCLUSION: Amenorrhea rates differed significantly by treatment arm, with the AT arm having the lowest rate. Patients treated with longer duration therapy (AC→T) had greater symptom severity and poorer QOL at 6 months, but did not differ from shorter duration treatments at 12 months.

Menstrual nirvana: amenorrhea through the use of continuous oral contraceptives.

Medically induced amenorrhea has been used successfully in women who have medical conditions that worsen during menstruation. Menstrual suppression through the use of continuous oral contraceptives has been proven to be safe, effective, and extremely acceptable to women. Women without medical indications for menstrual suppression may find medically induced amenorrhea to be a significant improvement in their quality of life. Greater satisfaction with use of oral contraception may encourage compliance and increase the prevalence of pill-related health benefits.

Program- and method-related determinants of first DMPA use duration in rural Bangladesh.

This article examines the determinants of first-time use durations of the injectable contraceptive Depo Medroxy Progesterone Acetate (DMPA) for rural Bangladeshi women. The method's side effects were defined by 200 first-time users in Matlab district during lengthy, open-ended interviews. Women with many children used the method longer than did women of low parity. Those who experienced side effects had shorter use durations than those who did not, and those who cited heavy bleeding as their main problem discontinued use soonest. Women whose husbands approved of family planning had significantly longer use durations than those whose husbands disapproved. Respondents who adopted DMPA because of perceived positive aspects of the drug used it longer than those who chose it for other reasons. Results of the study underscore the importance of viewing side effects in a specific social and cultural context. Expanded side-effects counseling for women and their husbands is needed.

PIP: During March-May 1990, in-depth interviews were conducted with 200 women who first accepted the injectable contraceptive depo-medroxyprogesterone acetate (DMPA) between July and August 1988 from the Maternal and Child Health and Family Planning program of the International Centre for Diarrhoeal Disease Research, Bangladesh in the rural Matlab district. The researchers analyzed the data to examine the determinants of first-time use durations of DMPA. 90% of the women chose DMPA because of negative experiences or fears of such experiences with other methods. Women who reported bleeding and nonbleeding side effects were more likely to have shorter use durations than those who reported no side effects (rate ratio [RR] = 1.83 and 3.07, respectively). Women who had heavy bleeding had the shortest use duration (median, 9 vs. 20 months for no problems). Amenorrhea was rarely considered to be the most significant problem linked to DMPA use. Women who chose DMPA because of its perceived positive aspects were more likely to have longer use duration than those who did not choose it for its positive aspects (RR = 0.38). Women who chose DMPA based on the community health worker's advise were more likely to have shorter use durations than those who did not choose it based on their advice (RR = 2.48). Women whose husbands approved of family planning were more likely to have longer use duration than those whose husbands did not approve (RR = 0.72). Multiparous women used DMPA longer than did those with less than 3 children (RR = 0.56 for 3-5 children and 0.36 for =or 6 children). These findings emphasize the importance of considering side effects in a social and cultural context to determine why they are important to women and which side effects are perceived as problematic and which are not. They also show the need to improve pre-use counseling and side effect management and to seek the support of husbands towards family planning.

The induction of amenorrhoea.

A survey has shown that many women favour eliminating menstruation and it has been suggested that therapeutic induction of amenorrhoea might be an advantage in female personnel mobilised for war. The traditional method has been to take the oral contraceptive pill continuously. This produces weight gain and other side-effects; spotting and breakthrough bleeding can be a problem initially. The method is however cheap. The Gonadotrophin Releasing Hormone (GnRH) analogue, goserelin, is extremely effective, produces less side-effects, but it is very expensive. Two synthetic steroids, danazol and gestrinone, are moderately effective, have a variety of prominent side-effects and are also quite expensive. With all these drugs normal menstruation resumes in the cycle after they are discontinued. Although goserelin has many advantages over the continuously taken contraceptive pill, its cost precludes it from consideration as a means of eliminating menstruation.

PIP: The Royal Army Medical Corps (RAMC) of the UK is considering offering women in the Army the option of inducing amenorrhea especially those in war. Logistics problems of supplying sufficient sanitary protection makes inducing amenorrhea in these women an advantage. It is important that the Royal Army not force servicewomen ready for war to agree to chemical induction of amenorrhea, however. A survey of civilian women shows that 80% liked the notion of eliminating menstruation. continuous combined oral contraceptive (COC) therapy induces amenorrhea, but it poses some side effects including bleeding and spotting, 2 kg weight gain, breast tenderness, depression, and headaches. 12 weeks of COC therapy costs range form 2 to 6 pounds. The synthetic androgen used to treat endometriosis, danazol, may also induce amenorrhea at daily doses of 800 mg. It causes various side effects including reduced breast size, flushing, sweating, loss of libido, acne, weight gain, edema, hirsutism, and voice change. 12-week danazol therapy costs about 200 pounds. Another drug with androgenic, antigonadotrophic, antiestrogenic, and antiprogestogenic properties which is also used to treat endometriosis, gestrinone, in another possible amenorrhea inducer at 2 doses of 2.5-5 mg/week. Side effects are similar to those of danazol. In 1 study, all 20 patients developed acne and seborrhea. Its 12 week costs are considerably more than danazol and COC therapy (450 pounds). Intermittent administration of 2 gonadotropin releasing hormone (GnRH) analogues, buserelin and goserelin, suppresses production of gonadotropins. Health workers need to inject 3.6 mg goserelin every 28 days while they administer buserelin subcutaneously or intranasally. the leading side effect on both GnRH analogues is not flushes. 12-week therapy is about 375 pounds. Fertility is restored after discontinuation of all the aforementioned therapies. The GnRH analogue goserelin is the most effective therapy, but the cost factor causes the Royal Army to favor COCs.

The McCormick Family Planning Program in Chiang Mai, Thailand.

The McCormick Family Planning Program is a private, single-purpose program that has been offering contraceptive services to women in largely rural Chiang Mai province in Northern Thailand since 1963. In addition to two clinics in Chiang Mai city, the program operates a mobile unit, which visits service points throughout the province. An injectable contraceptive, DMPA, has been selected by about two-thirds of program acceptors since 1965, despite its prevalent side effect of amenorrhea. The service generates sufficient revenues, from relatively low fees for sterilization and contraception, to cover most operating costs. The program is seen as successful in providing rural women with contraceptives services. Aspects of the program--particularly the use of DMPA and the mobile service unit--are considered replicable in other settings.

Efficacy and acceptability of injectable medroxyprogesterone. A comparison of 3-monthly and 6-monthly regimens.

Five hundred Black Rhodesian women given injections of 150 mg Depo-Provera every 3 months (group A) and 500 women given an injection of 450 mg Depo-Provera every 6 months (group B) were reviewed after 6 months. Group B had a significantly lower rate of defaulters. There was no significant difference between the groups with regard to weight gain, systolic and diastolic blood pressure increase, overall abnormal bleeding patterns and complaints of side-effects. Among those women who reported abnormal bleeding patterns, significantly more in group B had amenorrhoea. There was no significant increase of prolonged bleeding in group B. Among those women who complained of side-effects, significantly more in group B complained of headaches and a bloated abdomen. No pregnancies occurred in either group. The increased annual cost of the 450 mg injections, which was the main reason for women not accepting this regimen, is outweighed by convenience and reduced travel costs. Depo-Provera 450 mg given by 6-monthly injection is well tolerated and effective, and appears to be even more satisfactory as regards continued acceptance than 150 mg given every 3 months.

Perspectives in evaluating the safety and effectiveness of steroidal contraceptives in different parts of the world.

While differences in acceptability of steroidal contraceptives from nation to nation are generally recognized, variations in safety and effectiveness have been given little attention. Cardiovascular hazards such as thromboembolic disease, myocardial infarction, and stroke, which create such concern in developed countries, may be insignificant problems in other parts of the world where these diseases are rare in women of reproductive age. On the other hand, the influence of nutritional deficiencies, anemia, intestinal parasitism, malaria, and other widespread health problems on the effects and/or metabolism of steroids, which may be of major concern in developing countries, is just coming under study. Side effects also vary greatly among religiously and ethnically different populations, and significant differences in pregnancy protection and bleeding patterns among different populations have been reported-even with injectables. It is, therefore, important to examine and define intergroup differences and especially to recognize that safety concerns in one geographic setting cannot be automatically assumed to apply equally in other areas.

Clinical assessment of a low-dose oestrogen, low-dose progestogen combined oral contraceptive.

PIP: The efficacy, safety, and patient acceptance of an oral contraceptive containing 150 mcg d-norgestrel and 30 mcg ethinyl estradiol (150/30) were studied in 99 women who completed 754 cycles of medication between late 1971 and October 1973. 1 pregnancy occurred giving a pregnancy rate of 1.6 per 100 woman-years. This woman's previous history indicated unreliability in pill taking. The mean pretreatment length of menses was 4.9 days and during treatment, 4 days. Although intermenstrual bleeding and amenorrhea were noted in early cycles, there was a decrease in the usual incidence of headaches, nausea, vomiting, and depression. Results of the study and patients' acceptance suggest that the 150/30 combination may be used as the oral contraceptive of first choice.^ieng

Endocrine assessment of post-pill amenorrhoea.

PIP: 24 cases of postpill amenorrhea are presented. The patients were 17-34 years of age and the length of amenorrhea was 6-60 months with a mean of 13.4 months. There was no relationship between the type of contraceptive pill, length of usage, and the incidence of amenorrhea which suggests that the mechanism of action is general rather than due to a specific combination of steroid hormones. The basal endocrine status of the thyroid and adrenal was normal. 14 of the patients had low estrogen and gonadotropins and of these only 4 had a positive clomiphene pituitary reserve test. These 4 patients subsequently restarted normal cycles and luteinizing hormone/follicle stimulating hormone-releasing hormone tests showed normal pituitary function, indicating that the others probably had some derangement of hypothalamic pituitary function.^ieng