Bioidentical Oral 17ß-Estradiol and Progesterone for the Treatment of Moderate to Severe Vasomotor Symptoms of Menopause.

OBJECTIVE: To review the efficacy, safety, and available literature regarding the novel combination bioidentical product Bijuva, or 17ß-estradiol/progesterone (17ß-E/P), for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus. DATA SOURCES: Literature searches of both PubMed (1966 to October 2020) and Google Scholar were conducted using search terms including bioidentical, estradiol, progesterone, menopause, E2/P4, TX-001HR, and Bijuva. STUDY SELECTION AND DATA EXTRACTION: All articles with studies conducted in cisgender human females and in the English language were considered for review; 18 publications were included. DATA SYNTHESIS: In 1 phase 3 clinical study, 17ß-E/P was proven to be effective at reducing the frequency and severity of vasomotor symptoms (VMS) at 12 weeks compared with placebo, and no cases of endometrial hyperplasia were observed over the 52-week safety study period. Menopausal women with an intact uterus were included in the study population. RELEVANCE TO PATIENT CARE AND PRACTICE: Concerns over content and safety of compounded bioidentical hormones have been raised by several professional societies. As women experience VMS of menopause, a desire for a Food and Drug Administration-regulated bioidentical combination product for the treatment of moderate to severe menopausal symptoms may be desirable. Given as a once-daily oral capsule at the dose of 1 mg estradiol/100 mg progesterone, 17ß-E/P is approved for the treatment of VMS associated with menopause. CONCLUSIONS: 17ß-E/P is a novel bioidentical product that is the first of its kind in the treatment of moderate to severe menopausal symptoms.

Selective serotonin reuptake inhibitors for the treatment of irritable bowel syndrome.

OBJECTIVE: To evaluate the evidence investigating the use of selective serotonin reuptake inhibitors (SSRIs) for the treatment of irritable bowel syndrome (IBS). DATA SOURCES: A literature search was performed using PubMed (1950 through February 2014) for the MeSH terms serotonin reuptake inhibitor and irritable bowel syndrome; subterms of identified MeSH terms (ie, explosion) were also evaluated. EMBASE (1947 to February 2014) was searched using similar search terms. References from identified articles were checked and an updated Cochrane Database review was performed. STUDY SELECTION AND DATA EXTRACTION: All identified English-language peer-reviewed publications were evaluated. Articles (excluding meeting abstracts) specifically addressing SSRIs for the treatment of IBS were reviewed. The literature review was limited to randomized controlled trials (RCTs) conducted in human subjects. DATA SYNTHESIS: Fluoxetine, citalopram, and paroxetine have been studied for the treatment of IBS symptoms. Fluoxetine significantly improves abdominal pain, bloating, and stool consistency after 12 weeks of therapy, but these data contradict the findings of another 6-week study. Citalopram decreases abdominal discomfort after 6 to 12 weeks of treatment, but multiple studies have not shown an improvement in adequate relief of most IBS symptoms. Overall well-being was improved after 12 weeks of paroxetine use; however, IBS-related symptoms and social/work functioning were not improved. CONCLUSIONS: Available data evaluating the use of SSRIs in the treatment of IBS-related symptoms are conflicting. Additional larger RCTs lasting more than 12 weeks are needed to determine the place in therapy for SSRIs in the treatment of IBS-related symptoms.

Midodrine and octreotide in treatment of cirrhosis-related hemodynamic complications.

OBJECTIVE: To review studies evaluating the use of midodrine and octreotide in hemodynamic complications of cirrhosis, including ascites and hepatorenal syndrome. DATA SOURCES: Searches of MEDLINE (1966-September 2008) and EMBASE (1974-September 2008) were conducted using the terms midodrine, octreotide, hepatorenal syndrome, ascites, cirrhosis, and paracentesis-induced circulatory dysfunction. Literature review was limited to English-language, human studies. STUDY SELECTION AND DATA EXTRACTION: Studies identified from data sources were considered for review. Studies were excluded if primary therapy involved any of the following: transjugular intrahepatic portosystemic shunt procedure, medications other than midodrine or octreotide, or patients included for treatment or prevention of portal hypertension and/or variceal bleeding. Pharmacokinetic/pharmacodynamic studies and studies using retrospective data collection were excluded. Seven studies were included in this review. DATA SYNTHESIS: Midodrine and octreotide in combination or alone have shown conflicting results for systemic and renal hemodynamics and renal function in patients with cirrhosis-related complications. Patients with ascites being treated with midodrine, alone or in combination with octreotide, showed significant changes in systemic hemodynamics, without a correlating change in renal perfusion. Studies comparing the use of midodrine with use of albumin for the prevention of paracentesis-induced circulatory dysfunction (PICD) showed no incidence of PICD in either treatment group. In hepatorenal syndrome, patients using midodrine with octreotide showed significant changes in systemic hemodynamics and improvements in renal perfusion. This regimen's effect on survival is yet to be determined. CONCLUSIONS: Available evidence shows inconsistent results for the effectiveness and safety of midodrine and octreotide use in cirrhotic patients. Because of the contradictory results, longer treatment duration and increased number of study participants are necessary to determine the proper use of midodrine and octreotide in these patients.

Once-yearly administered intravenous zoledronic acid for postmenopausal osteoporosis.

OBJECTIVE: To review studies that investigated the use of once-yearly administered intravenous zoledronic acid for the treatment of postmenopausal osteoporosis. DATA SOURCES: Searches of MEDLINE (1966-February 2008) and EMBASE (1974-February 2008) were conducted using the terms zoledronic acid, once-yearly, and postmenopausal osteoporosis. Literature review was limited to human studies. STUDY SELECTION AND DATA EXTRACTION: All literature identified from the data sources was evaluated for review inclusion. Studies investigating the use of zoledronic acid in conditions other than postmenopausal osteoporosis, including malignant hypercalcemia, multiple myeloma, and Paget's disease, were excluded. Five randomized controlled studies were included in this review. DATA SYNTHESIS: Oral bisphosphonates represent one of the most commonly prescribed drug classes for the treatment of postmenopausal osteoporosis. However, due to poor gastrointestinal absorption and poor patient adherence to bisphosphonate therapy, once-yearly intravenous zoledronic acid may be a more attractive option for some patients. Once-yearly zoledronic acid has been shown to decrease bone turnover markers such as serum C-telopeptide by 49-52%, decrease the vertebral fracture rate by approximately 70%, and significantly increase bone mineral density at total hip, femoral neck, and lumbar spine by 6.02%, 5.06%, and 6.71%, respectively. Furthermore, some women may prefer the convenience of once-yearly intravenous zoledronic acid to daily or weekly oral bisphosphonates. In clinical trials that compared once-yearly zoledronic acid infusion with weekly oral alendronate, participants preferred zoledronic acid and found its adverse effect profile to be more favorable. CONCLUSIONS: Based on available evidence, once-yearly zoledronic acid is an efficacious treatment option for postmenopausal women with osteoporosis. However, lack of head-to-head studies with oral bisphosphonates is a limitation in evaluating its clinical utility. Additional studies investigating zoledronic acid against oral bisphosphonates, specifically looking at rates and types of fractures, are needed to fully determine its place in postmenopausal osteoporosis treatment.

A review of osteoporosis management in younger premenopausal women.

The purpose of this review is to describe the available evidence for osteoporosis treatments in young and premenopausal women. A review of articles evaluating the treatment or prevention of osteoporosis in young (age less than 50 years) or premenopausal women was conducted. Several trials evaluating the treatment of anorexia nervosa and use of hormone therapy in those women, the use of bisphosphonates in women undergoing chemotherapy for breast cancer and the use of bisphosphonates, teriparatide and vitamin D in women with glucocorticoid-induced osteoporosis are described. Limited data were found to support the treatment of osteoporosis in women with idiopathic osteoporosis or cystic fibrosis, or after kidney transplant. The evidence for treatment of osteoporosis in premenopausal women is not nearly as robust as that for postmenopausal osteoporosis. Although fracture risk in the premenopausal population is low, women with secondary osteoporosis may benefit from treatment with various agents, depending upon the condition.

Ospemifene for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women.

Vulvovaginal atrophy (VVA) and dyspareunia are common problems experienced by postmenopausal women, although few seek treatment. Symptom-based therapies include nonhormonal vaginal lubricants, vaginal moisturizers, low-dose vaginal estrogen, and systemic estrogen. The 2013 United States Food and Drug Administration approval of ospemifene, an estrogen agonist/antagonist for the treatment of moderate-to-severe dyspareunia associated with VVA, increased options available to women. Several studies have evaluated the effects of ospemifene on VVA and dyspareunia and indicate an improvement in subjective findings. Objective findings such as a decrease in pH and recovery of a premenopausal vaginal maturation index have been reported. Beneficial effects have also been demonstrated in bone. Evaluations of breast health support the safety of ospemifene, although data are limited to 1 year. Short-term risks appear to be limited and include the development of hot flushes. Until additional comparative studies of ospemifene and estrogens have been performed, ospemifene should be recommended for women with symptoms of VVA and dyspareunia who are unable to tolerate or unwilling to take local or systemic estrogens. In this review, current evidence for the safety and efficacy of ospemifene in the treatment of moderate-to-severe VVA and dyspareunia are evaluated.

Testosterone supplementation for hypoactive sexual desire disorder in women.

Over 50% of women are believed to be affected by female sexual dysfunction (FSD). When particularly distressful, FSD is known as hypoactive sexual desire disorder (HSDD). In contrast to male sexual dysfunction that has been extensively researched, there is less evidence addressing the treatment of HSDD in women, particularly with regard to the use of androgen therapy. A variety of testosterone products, including oral, injectable, and transdermal preparations, has been prescribed for the treatment of HSDD in premenopausal women, as well as in those with naturally occurring or surgically induced menopause. Although studies have shown some benefit with testosterone supplementation in women with HSDD, conflicting evidence and debate regarding the clinical efficacy of testosterone remain. Because of concern over potential adverse events, additional studies with longer follow-up periods are necessary before use of testosterone in women with HSDD becomes widespread. Initiation of testosterone therapy must be considered on an individual basis after a thorough discussion with the patient about risks and benefits.

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.

Hormone therapy for the management of menopausal symptoms: pharmacotherapy update.

Nearly 50 million women each year are projected to reach menopause by 2030. Many of these women will experience vasomotor symptoms such as night sweats and hot flashes as they enter the menopausal transition. Up until the release of the findings of the Women's Health Initiative (WHI) studies, women were frequently prescribed hormone therapy (HT) to alleviate bothersome and sometimes debilitating menopausal symptoms as well as to prevent osteoporosis and coronary heart disease (CHD). Although the WHI studies were the first large, randomized, controlled trials that contradicted what was historically believed about the benefits of HT in postmenopausal women, important limitations including baseline demographics of WHI participants and investigation of only one HT strength/dosage form exist. HT may be a reasonable pharmacotherapy option for the management of menopausal symptoms following complete patient evaluation by experienced clinicians. Updated recommendations addressing management of menopausal symptoms, a new HT product containing the spironolactone-analogue drospirenone (DRSP), and discontinuation methods of HT are also discussed in this review.