Life-threatening vaginal bleeding after starting rivaroxaban treatment.

This is a case report of a 44-year-old premenopausal woman who was admitted to hospital due to uncontrollable and life-threatening vaginal bleeding after starting rivaroxaban treatment for atrial fibrillation. She had a medical history with menorrhagia due to an intrauterine fibroma. She did not respond sufficiently to factor X supplement or other non-surgical medical interventions. The bleeding subsided after bilateral embolization of aa. uterinae.

Causal association between lipid-lowering drugs and female reproductive endocrine diseases: a drug-targeted Mendelian randomization study.

Purpose: The relationship between dyslipidemia and female reproductive endocrine diseases has been increasingly studied. The use of lipid-lowering drugs in treating various related diseases, including coronary heart disease, may affect female reproductive endocrine diseases. Therefore, our study aims to investigate the effects of lipid-lowering drugs on female reproductive endocrine diseases and provide a basis for the appropriate selection of drugs. Methods: In this study, we focused on three drug targets of statins, namely HMG-CoA reductase (HMGCR) inhibitors, proprotein convertase kexin 9 (PCSK9) inhibitors, and Niemann-Pick C1-Like 1 (NPC1L1) inhibitors. To identify potential inhibitors for these targets, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR, PCSK9, and NPC1L1 from published genome-wide association study statistics. Subsequently, we conducted a drug target Mendelian randomization (MR) analysis to investigate the effects of these inhibitors on reproductive endocrine diseases mediated by low-density lipoprotein cholesterol (LDL-C) levels. Alongside coronary heart disease as a positive control, our main outcomes of interest included the risk of polycystic ovary syndrome (PCOS), premature ovarian insufficiency (POI), premenstrual syndrome (PMS), abnormal uterine bleeding (including menorrhagia and oligomenorrhea), and infertility. Results: PCSK9 inhibitors significantly increased the risk of infertility in patients (OR [95%CI] = 1.14 [1.06, 1.23], p<0.05). In contrast, HMGCR inhibitors significantly reduced the risk of menorrhagia in female patients (OR [95%CI] = 0.85 [0.75, 0.97], p<0.05), but had no statistical impact on patients with oligomenorrhea. Conclusion: The findings suggest that PCSK9 inhibitors may significantly increase the risk of infertility in patients. On the other hand, HMGCR inhibitors could potentially offer protection against menorrhagia in women. However, no effects of lipid-lowering drugs have been observed on other reproductive endocrine disorders, such as PCOS, POF, PMS and oligomenorrhea.

A plain language summary of the long-term relugolix combination therapy study for uterine fibroids.

What is this summary about? This is a summary of a research study (known as a clinical trial) called the LIBERTY extension study. The LIBERTY extension study is a long-term study looking at how well a medicine called relugolix combination therapy worked in reducing blood loss during menstrual periods in women with uterine fibroids with heavy menstrual periods. Women were included in the extension study if they finished the 24-week LIBERTY 1 or LIBERTY 2 studies. Heavy menstrual periods were considered to be menstrual blood loss of about one-third of a cup of blood (80 ml) per cycle for two cycles or about two-thirds of a cup of blood (160 ml) during one cycle. The LIBERTY extension study also looked at whether relugolix combination therapy was safe to take for up to 1 year. What were the results? Out of 770 total women with uterine fibroids with heavy menstrual bleeding who took part in the LIBERTY 1 and LIBERTY 2 studies, 476 took part in the LIBERTY extension study. From the start of the LIBERTY 1 and LIBERTY 2 studies through the end of the LIBERTY extension: 163 women took relugolix combination therapy for 52 weeks 149 women took relugolix alone for 12 weeks followed by relugolix combination therapy for 40 weeks 164 women took placebo for 24 weeks followed by relugolix combination therapy for 28 weeks The LIBERTY extension study showed that most women in all three treatment groups responded to relugolix combination therapy by having less bleeding during their menstrual periods, having improved anemia symptoms, and having stable bone mineral loss. Side effects were similar across treatment groups, and the most common side effects were headaches and hot flushes. What do the results mean? Women with uterine fibroids with heavy menstrual bleeding taking relugolix combination therapy may have fewer uterine fibroid bleeding symptoms for up to 1 year of treatment. Clinical Trial Registration: NCT03049735 (ClinicalTrials.gov) (LIBERTY 1) Clinical Trial Registration: NCT03103087 (ClinicalTrials.gov) (LIBERTY 2) Clinical Trial Registration: NCT03412890 (ClinicalTrials.gov) (LIBERTY extension study).

A plain language summary of the safety of relugolix combination therapy and improvement in symptoms in women with uterine fibroids from the LIBERTY 1 and LIBERTY 2 studies.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of research studies (known as clinical trials) called LIBERTY 1 and LIBERTY 2. The LIBERTY 1 and LIBERTY 2 studies looked at how well a medication called relugolix combination therapy worked to reduce heavy bleeding at the time of menstruation compared with placebo. The studies also looked at what side effects were reported in women with uterine fibroids and heavy menstrual bleeding. WHAT WERE THE RESULTS?: Researchers looked at 388 adult women in the LIBERTY 1 study and 382 adult women in the LIBERTY 2 study. All women had heavy menstrual bleeding with uterine fibroids before the start of the LIBERTY 1 and LIBERTY 2 studies. The women were given one of three treatments during the studies: relugolix combination therapy or placebo for 24 weeks, or delayed relugolix combination therapy (relugolix alone for the first 12 weeks, then relugolix combination therapy for the last 12 weeks of the studies). More women taking relugolix combination therapy in the LIBERTY 1 study (73%) and LIBERTY 2 study (71%) had menstrual blood loss of less than one-third of a cup (80 mL) and had reduction of at least 50% less blood loss during their last menstrual period after 24 weeks of taking the medicine compared with placebo (LIBERTY 1: 19% and LIBERTY 2: 15%). The women taking relugolix combination therapy also had less pain than those taking placebo. Side effects were similar across treatment groups. Headaches and hot flushes were the most common side effects. WHAT DO THE RESULTS MEAN?: More women with uterine fibroids taking relugolix combination therapy for 24 weeks were likely to have fewer uterine fibroid symptoms than women receiving placebo. Clinical Trial Registration: NCT03049735 (LIBERTY 1); NCT03103087 (LIBERTY 2).

Effects of long-term intermittent pharmacological therapy with ulipristal acetate on reducing the volume of uterine fibroids and relieving symptoms.

BACKGROUND: The aim of this study was to compare the effects of a 12-week course and four repeated 12-week courses of daily 5 mg ulipristal acetate (UPA) on reducing the volume and relieving symptoms of uterine fibroids. METHODS: From 2016 to 2019, 287 female patients with uterine fibroids diagnosed using ultrasonography were recruited. The patients received four 12-week course treatments of daily UPA administration in the first and fourth sessions, respectively. During the first and fourth courses of UPA, we measured the volume of the fibroids using ultrasonography to study the effect on volume reduction. The measured outcomes included symptomatic relief and adverse effects. RESULTS: After the first UPA treatment course, menorrhagia was improved in 82.2% of patients. A total of 59.5% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 160.9 cm3 to 104.6 cm3. After the fourth treatment course, 87.4% of patients reported decreased bleeding. A total of 67.2% of patients were responsive to treatment, and the volume of the three largest fibroids decreased from 171.7 cm3 to 106.5 cm3. In 64 (38.1%) patients in group A and 36 (30.3%) in group B, the fibroid volume increased. Among them, 72% of patients showed improved symptoms. CONCLUSIONS: Uterine bleeding, pain, and reduced fibroid volume were adequately regulated in patients with symptomatic fibroids with four repeated 12-week courses of daily UPA.

Evaluation of oral tranexamic acid as a novel treatment for melasma with a high benefit-risk ratio.

BACKGROUND: Melasma is an acquired melanogenesis dysfunction resulting in chronic hyperpigmentation commonly affecting the face and other frequently sun-exposed areas of the body. Melasma typically presents in women of reproductive age and can significantly impact self-esteem, negatively affecting one's quality of life. In the United States, melasma is often treated with application of topical agents that interfere with melanin synthesis, lasers, or chemical peels; however, in some East Asian countries, oral tranexamic acid (TXA) is widely administered to alleviate hyperpigmentation during and after childbirth. TXA is currently only FDA-approved to treat hypermenorrhea and reduce blood loss in surgery but may offer women in the United States an additional therapeutic option to treat melasma. AIMS: The aim of this paper is to evaluate the safety and baseline efficacy of oral transmexic acid as a treatment for melasma. METHODS: We retrospectively surveyed 42 patients of Fitzpatrick skin types III-VI that were prescribed 650 mg of TXA ½ tablet to be taken twice daily by mouth. RESULTS: We found majority of patients saw noticeable improvement in their melasma. Of the 42 patients, only seven experienced side effects. The side effects noted were headaches, malaise and nausea, gastrointestinal upset, congestion, numbness in legs, hypomenorrhea, and hypermenorrhea. Patients who experienced unpleasant side effects discontinued taking oral TXA and were relieved of their symptoms. No long-term side effects were discovered, and the side effects experienced may be due to other confounding factors. CONCLUSION: From this data, we concluded oral TXA is a safe and effective treatment option for patients with persistent melasma.

Prolonged use of finasteride-induced gonadal sex steroids alterations, DNA damage and menstrual bleeding in women.

The aim of the present study was to examine the effect of prolonged use of finasteride on serum levels of dihydrotestosterone (DHT), estradiol (E2), progesterone, testosterone and androstenedione in women during the menstrual period. Further, to screen and compare the 5α-reductase activities through the expression of SRD5A1, SRD5A2 and AR gene and to determine the level of VEGF, VKOR and SAA gene expression and DNA damage. A total of 30 Saudi women aged between 25 and 35 years were enrolled in the study. The selected women were divided into two groups. The first group (n = 15) received 5 mg finasteride/day for prolonged period of one year and second group (n = 15) was taken as a healthy control. ELISA technique was used for measuring the serum levels of the targeted hormones, and Comet assay was used for checking the DNA integrity. Our findings revealed significant decrement of DHT, E2, progesterone and androstenedione levels and elevated levels of testosterone in group treated with daily oral doses of 5 mg finasteride/day compared with the control subjects. mRNA expression suggested that finasteride has concrete effects on the gene expression of the selected genes from the treated group in comparison with the control group. In addition, finasteride induced DNA damage, and heavy menstrual bleeding was noted in women treated with finasteride. In conclusion, the present findings revealed that finasteride has adverse health effects in women associated with gonadal sex steroids alterations, DNA damage and heavy menstrual bleeding with no consensus in the treatment of androgenetic alopecia in women.

Management of heavy menstrual bleeding during direct oral anticoagulant therapy for recurrent venous thromboembolism: a case report.

: A high risk of venous thromboembolism (VTE) recurrence requires extended anticoagulation but limits the options to control heavy menstrual bleeding (HMB) in women of reproductive age. We report the management of HMB in a 48-year-old woman with a history of menometrorrhagia, recurrent VTE and multiple VTE risk factors. Due to the occurrence of HMB during extended rivaroxaban treatment, the presence of a uterine fibroid and the contraindication to interrupt anticoagulation for high risk of VTE recurrence, she received hormonal treatment first with a gonadotropin-releasing hormone agonist and then with progestin. This strategy allowed to adequately control HMB, without rivaroxaban discontinuation or dose reduction, and no new thromboembolic and no more bleeding events occurred over a long follow-up period of more than 20 months. In conclusion, the use of hormonal therapy in VTE women requiring long-term anticoagulation may be an option to control HMB, without further increasing the risk of VTE recurrence.

Gynecologic Bleeding Complications in Postmenarchal Female Adolescents Receiving Antithrombotic Medications.

STUDY OBJECTIVE: The prevalence, clinical features, and management of gynecologic bleeding complications and health care provider awareness of these in postmenarchal adolescents receiving antithrombotic medications has rarely been addressed in the literature. We sought to address these issues in a review of our experience in a pediatric tertiary care center. DESIGN, SETTING, AND PARTICIPANTS: A retrospective chart review was conducted with institutional review board approval from 2004 to 2014, on eligible postmenarchal adolescents receiving antithrombotic medications. Descriptive statistics were used. RESULTS: Sixty-eight adolescents received antithrombotic medications (thromboembolism in 67 of 68; 99%; cardiac causes in 4 of 68; 6%), which included enoxaparin, warfarin, unfractionated heparin, alteplase, fondaparinux, and aspirin. Heavy menstrual bleeding (HMB) screening questions were documented by treating hematologists in 52 of 68 patients (76%; 95% confidence interval, 65%-86%). Adolescent gynecology consult was requested for 25 of 68 patients (37%). After antithrombotic medications were started, 13 of 68 (19%) developed HMB. Anemia was found in 43% of patients tested (18 of 42); 50% (9 of 18) and 78% patients (14 of 18) received packed red blood cell transfusion and iron therapy, respectively. Five patients (5 of 68; 7%) developed hemorrhagic ovarian cysts, 40% (2 of 5) were treated with surgery, 16% (1 of 5) received transfusions, and 100% (5 of 5) received or continued progesterone-only therapy with no recurrence. CONCLUSION: Adolescents receiving antithrombotic medications are at risk of developing gynecologic bleeding complications, which can result in anemia, hospitalization, transfusions, or surgery. Provider awareness/screening of HMB as a bleeding complication of antithrombotic medications is less than optimal. Future prospective studies in adolescents receiving antithrombotic medications are needed to better evaluate provider awareness and the prevalence of gynecologic bleeding complications, which can lead to effective management.

Assessment of urinary cotinine levels in women with gynecological complaints at a tertiary care hospital: A pilot study.

Gynecological effects due to smokeless tobacco exposure are not well studied. This cross-sectional study was undertaken with the objective to evaluate the urinary cotinine levels in women of reproductive age with gynecological complaints. The study was conducted in 2015 at the outpatient clinic of the Department of Obstetrics and Gynecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi. A total of 192 consecutive women presenting with gynecological complaints (pelvic inflammatory disease (PID), infertility, and menstrual abnormality) were recruited. Their demographic details and tobacco exposure were recorded. All of them denied exposure to any form of tobacco. Urinary cotinine level of each participant was measured. The mean urinary cotinine level was 23.60 ± 12.00 ng/ml. PID was the most common gynecological complaint. Women with PID had significantly higher urinary cotinine levels compared to those with menstrual complaints and infertility: 24.9548 (±12.259) ng/ml versus 20.2042 (±10.9248) ng/ml. This study highlights the importance of addressing the issue of secondhand smoke exposure and reproductive morbidities in women.

Management and outcomes of vaginal bleeding and heavy menstrual bleeding in women of reproductive age on direct oral anti-factor Xa inhibitor therapy: a case series.

BACKGROUND: Observational data and results from post-hoc analyses in clinical trials suggest that direct oral factor Xa inhibitors might increase menstrual bleeding intensity in women of reproductive age, but the extent of this effect is unknown. We aimed to investigate the management and outcomes of vaginal bleeding complications during therapy with direct oral factor Xa inhibitors in a case series of women of reproductive age. METHODS: To identify individuals for inclusion in this case series, we searched two sources of prospectively collected data from women of reproductive age treated with direct oral factor Xa inhibitors: the non-interventional Dresden NOAC Registry (NCT01588119), which is based in the administrative district of Dresden (Saxony, Germany), and all locally archived data from phase 3 trials of direct oral factor Xa inhibitors done at University Hospital Carl Gustav Carus Dresden. Vaginal bleeding events were defined as any vaginal bleeding complications as reported by the patient. We collected data on type and dosage of anticoagulation; suspected or confirmed bleeding events, hospital admissions, and mortality; and pattern and management of vaginal bleeding events. For all cases of bleeding identified, we reviewed all available source data to identify examination results suggesting potential underlying anatomical causes of bleeding. FINDINGS: We identified 178 women of reproductive age who received direct oral factor Xa inhibitor therapy, of whom 57 had vaginal bleeding events, including 50 who received rivaroxaban, six who received apixaban, and one who received edoxaban. These 57 women had 72 vaginal bleeding events, including 59 cases of heavy menstrual bleeding and 13 bleeding events unrelated to the menstrual cycle. 51 (86%) of these heavy menstrual bleeding events (two major bleeding events, 17 clinically relevant non-major bleeding events, 32 minor bleeding events) were treated conservatively (eg, change of oral hormone therapy or reduction, temporary interruption, or discontinuation of direct oral factor Xa inhibitor) and the remaining eight (14%) events (three major bleeding events and five clinically relevant non-major bleeding events) required elective surgical or interventional treatment (hysterectomy, curettage, ovary excision, or excision of ovarian cysts). Of the 57 women, 13 (23%) had a second bleeding event and two (4%) had a third event. Nine patients had underlying anatomical abnormalities; compared with patients without abnormalities, these patients had more intense bleeding, more had recurrent bleeding (five [56%] of nine patients with abnormalities vs eight [17%] of 48 patients without abnormalities), and more needed surgical treatment for bleeding (eight [89%] of nine vs zero of 48). INTERPRETATION: Vaginal bleeding, particularly heavy menstrual bleeding, is a common complication in women of reproductive age on direct oral factor Xa inhibitor therapy. Most cases can be treated conservatively, but patients with severe or recurrent vaginal bleeding complications should be assessed for underlying anatomical abnormalities, which might require surgical or interventional treatment. Further data are needed to provide guidance on prevention and treatment of vaginal bleeding complications in this patient population. FUNDING: None.

A comparison of bleeding patterns and cycle control using two transdermal contraceptive systems: a multicenter, open-label, randomized study.

OBJECTIVE(S): To investigate the bleeding pattern and cycle control parameters of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a patch containing 0.6 mg EE and 6 mg norelgestromin (NGMN). STUDY DESIGN: In this phase III, open-label, randomized, parallel-group trial, healthy women aged 18-35 years (smokers aged 18-30 years) received either the EE/GSD patch (n=200) or the EE/NGMN patch (n=198). Treatment consisted of one patch per week for 3 weeks followed by a 7-day, patch-free interval for seven cycles. Bleeding control was assessed in two 90-day reference periods. RESULTS: In reference period 1, mean number of bleeding/spotting days was comparable across treatment groups (p>0.05). However, in reference period 2, there were fewer bleeding/spotting days in the EE/GSD patch group (15.7 versus 18.4; p<0.0001). Mean number of bleeding/spotting episodes was comparable across groups for both reference periods, but bleeding/spotting episodes were shorter for the EE/GSD patch than the EE/NGMN patch during reference period 1 (5.13 days versus 5.53 days, respectively; p<0.05) and reference period 2 (5.07 versus 5.66; p=0.0001). Both treatment groups showed a similar frequency of withdrawal bleeding episodes; however, across all seven cycles, the length of these episodes was consistently shorter with the EE/GSD patch (p<0.01). There were no notable treatment differences in intracyclic bleeding. CONCLUSION(S): Bleeding pattern and cycle control achieved with the EE/GSD patch was similar to that of the EE/NGMN patch. IMPLICATIONS STATEMENT: The paper presents data on the bleeding pattern and cycle control parameters of an investigational transdermal contraceptive patch containing EE and GSD compared with an approved contraceptive patch containing EE and NGMN. This descriptive study found that bleeding patterns associated with the EE/GSD patch were similar to those of an EE/NGMN patch providing higher EE exposure.

Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study.

OBJECTIVE(S): The aim of this study was to investigate the bleeding pattern and cycle control of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a combined oral contraceptive (COC) containing 0.02 mg EE and 0.1 mg levonorgestrel (LNG). STUDY DESIGN: In this phase III, randomized, controlled, double-blind, double-dummy, multicenter trial, healthy women aged 18-45 years (smokers aged 18-35 years) received either the EE/GSD patch and a placebo tablet (n=171), or a placebo patch and the COC (n=175) for seven 28-day cycles. Bleeding control was assessed in two 90-day reference periods. RESULTS: Mean number of bleeding/spotting days was comparable across treatment groups in both reference periods (p>.05). Mean number of bleeding/spotting episodes was also comparable in reference period 1; however, there were fewer bleeding/spotting episodes for COC in reference period 2 (3.4 versus 3.1; p=.01). Mean length of bleeding/spotting episodes was comparable across treatment groups for both reference periods (p>.05). Withdrawal bleeding occurred consistently in both groups over the entire treatment period, but its absence was more common in the COC group in cycles 4 and 6 of reference period 2 (p<.01). Intracyclic bleeding was comparable between groups. CONCLUSION(S): Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC. IMPLICATIONS STATEMENT: The findings suggest that bleeding patterns with the EE/GSD patch are similar to an EE/LNG-containing COC, except for absence of withdrawal bleeding, which was less common in patch users. The EE/GSD patch may constitute an additional contraceptive option for women.

Management of uterine bleeding during hematopoietic stem cell transplantation.

BACKGROUND: Hematopoietic stem cell transplant is an effective treatment strategy for a variety of hematologic disorders, but patients are at risk for dysfunctional coagulation and abnormal bleeding. Gynecologists are often consulted before transplant for management of abnormal uterine bleeding, which may be particularly challenging in this context. CASE: A premenopausal woman with MonoMAC (a rare adult-onset immunodeficiency syndrome characterized by monocytopenia and Mycobacterium avium complex infections resulting from mutations in GATA2, a crucial gene in early hematopoiesis) presented with pancytopenia, evolving leukemia, and recent strokes, necessitating anticoagulation. During preparation for hematopoietic stem cell transplant, she experienced prolonged menorrhagia requiring transfusions. Surgical therapy was contraindicated, and medical management was successful only when combined with balloon tamponade. CONCLUSION: Balloon tamponade may be a potentially life-saving adjunct to medical therapy for control of uterine hemorrhage before hematopoietic stem cell transplant.

Management of menorrhagia associated with chemotherapy-induced thrombocytopenia in women with hematologic malignancy.

Abnormal uterine bleeding in women with a blood dyscrasia, such as leukemia, or who experience thrombocytopenia secondary to myelosuppressive chemotherapy is a clinical condition associated with significant morbidity. Consequently, effective management is necessary to prevent adverse outcomes. Prevention of menorrhagia, defined as heavy regular menstrual cycles with more than 80 ml of blood loss/cycle or a cycle duration longer than 7 days, in this patient population is the goal of therapy. Gonadotropin-releasing hormone analogs (e.g., leuprolide) are promising therapies that have been shown to decrease vaginal bleeding during periods of thrombocytopenia and to have minimal adverse effects other than those associated with gonadal inhibition. In patients who experience menorrhagia despite preventive therapies, or in patients who have thrombocytopenia and menorrhagia at diagnosis, treatment is indicated. For these women, treatment options may include platelet transfusions, antifibrinolytic therapy (e.g., tranexamic acid), continuous high-dose oral contraceptives, cyclic progestins, or other therapies for more refractory patients such as danazol, desmopressin, and recombinant factor VIIa. Hormonal therapies are often the mainstay of therapy in women with menorrhagia secondary to thrombocytopenia, but data for these agents are sparse. The most robust data for the treatment of menorrhagia are for tranexamic acid. Most women receiving tranexamic acid in randomized trials experienced meaningful reductions in menstrual bleeding, and this translated into improved quality of life; however, these trials were not performed in patients with cancer. Further clinical trials are warranted to evaluate both preventive and therapeutic agents for menorrhagia in premenopausal women with cancer who are receiving myelosuppressive chemotherapy.

Centchroman: is unsupervised long-term use warranted? Case report.

OBJECTIVES: Centchroman (Ormeloxifene) is a synthetic non-steroidal compound used as an oral and a post-coital contraceptive. It is currently under trial for treatment of breast cancer and postmenopausal osteoporosis. Centchroman has been reported to induce only minimal side effects and no hormonal imbalance. CASE: A young woman who used centchroman for a long time in an unsupervised fashion presented with menorrhagia, which was controlled with norethisterone. Her massively enlarged uterus showed extensive decidual changes in a hyperplastic endometrium, and diffuse microglandular cervical hyperplasia. CONCLUSIONS: The case suggests a prominent oestrogenic effect of centchroman on the uterus. This could be a significant adverse effect related to prolonged therapy. Lengthy intake of centchroman requires medical surveillance and long-term studies are needed.

Menorrhagia and severe menstrual pain related to the use of adalimumab in a psoriatic.

The case is reported of a 32-year-old morbidly obese white woman who used adalimumab 40 mg every other week for 4 months for psoriatic arthritis, psoriasis vulgaris and inverse psoriasis with total clearance of her psoriasis who developed menorrhagia (at least twice the number of pads used daily for 4-6 days as opposed to 3-5 days previously) and severe menstrual pain. Treatment with Aviane (ethinyl estradiol and levonorgestrel) abated some of these menstrual symptoms. The symptoms resolved altogether when the adalimumab was discontinued. Menstrual disorders are listed as possible side effects from the use of infliximab and adalimumab in their respective package inserts and also for adalimumab and etanercept in the United Kingdom's Medicines and Healthcare products Regulatory Agency's drug side-effect database, but few case reports of menstrual side effects exist from including tumor necrosis alpha (TNFalpha) blockers. Physicians should be aware of the menstrual side effects of adalimumab and the role of oral contraceptive pills in treating such menstrual side effects.

A novel estrogen-free oral contraceptive pill for women: multicentre, double-blind, randomized controlled trial of mifepristone and progestogen-only pill (levonorgestrel).

BACKGROUND: The acceptability and continuation rate of oral contraceptive steroids are limited by unpredictable bleeding and the fear of long-term risks such as breast cancer. By inhibiting ovulation and by altering the receptivity of the endometrium, antagonists of progesterone, such as mifepristone, could be developed as estrogen-free novel contraceptives. METHODS: Multicentre, double-blind, randomized controlled trial comparing frequency of amenorrhoea (primary outcome), bleeding patterns, side effects and efficacy in women taking daily 5 mg mifepristone (n = 73) or 0.03 mg levonorgestrel (progestogen-only pill; POP, n = 23) for 24 weeks. RESULTS: More women were amenorrhoeic while taking mifepristone than POP (49 versus 0% P < 0.001), and fewer women bled or spotted for >5 days per month (4 versus 39% P < 0.001). Forty-eight percent of women who took mifepristone for 6 months had cystic glandular dilatation of the endometrium but none showed hyperplasia or atypia. There were no pregnancies in 356 months of exposure in women who used only mifepristone for contraception. Two pregnancies occurred in women taking mifepristone who were also using condoms for dual protection. CONCLUSIONS: Daily mifepristone (5 mg) is an effective oral contraceptive pill which has a better pattern of menstrual bleeding than an existing POP (levonorgestrel).

Menometrorrhagia and tachyarrhythmia after using oral and topical ginseng.

Widespread and uncontrolled use of ginseng has raised the question of its side effects and drug interactions. A 39-year-old female patient experienced menometrorrhagia. Her complaints had started 5 months earlier. The laboratory tests revealed follicle-stimulating hormone (FSH) and estradiol levels to be 10 mIU and 90 mIU, respectively. Endometrial biopsy was planned for the diagnosis of abnormal uterine bleeding. During the preoperative evaluation, the patient stated that she had been using both oral and topical ginseng for cosmetic reasons. The ECG revealed sinus tachycardia with occasional atrial premature beats. The procedure was postponed for 2 weeks so that the patient would stop taking ginseng, smoking, and drinking coffee. Arrhythmia stopped 10 days later. Tachycardia continued during the procedure but did not require treatment, as it did not cause any hemodynamic instability. An endometrial biopsy specimen showed a disordered proliferative pattern. The patient was advised to stop using oral and topical ginseng. During a follow-up visit, she had no sign of menometrorrhagia or tachyarrhythmia and her hemoglobin levels were in the normal range. Smoking and coffee consumption, along with ginseng use, can be responsible for arrhythmogenic effects. Abnormal uterine bleeding can cause tachycardia secondary to anemia. The clinical progress of this patient is consistent with our hypothesis that ginseng is responsible for menometrorrhagia, although this could be coincidental. Patients should always be asked prior to surgery if they use herbal medications, food supplements, or cosmetics as well as prescription drugs. This is of great importance for both diagnosis and avoidance of drug interactions and side effects during anesthesia.