Polycystic ovarian syndrome-current pharmacotherapy and clinical implications.

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women is characterized by polycystic ovaries, chronic anovulation and hyperandrogenism. The treatment in PCOS is mainly symptomatic and involves lifestyle interventions and medications such as Metformin, Oral contraceptives and Antiandrogens. However, the management of PCOS is challenging and current interventions are not able to deal with outcomes of this syndrome. This review encompasses latest pharmacotherapeutic and non-pharmacotherapeutic interventions currently in use to tackle various symptomatic contentions in PCOS. Our focus has been mainly on novel therapeutic modalities for treatment/management of PCOS, like use of newer insulin sensitizers viz., Inositols, Glucagon-like peptide-1(GLP-1) agonists, Dipeptidyl pepdidase-4 (DPP-4) inhibitors, and sodium-glucose transport protein 2 (SGLT2) inhibitors. Also, evidence suggesting the use of vitamin D, statins, and Letrozole as emerging therapies in PCOS have been summarized in this review. Additionally, novel cosmetic techniques like electrolysis, laser and use of topically applied eflornithine to tackle the most distressing feature of facial hirsutism associated with PCOS, non-pharmacological therapy like acupuncture and the role of herbal medicine in PCOS management have also been discussed.

Combination of Intense Pulse Light and Topical Eflornithine Therapy versus Intense Pulse Light Therapy alone in the Treatment of Idiopathic Facial Hirsutism: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of combination of Intense Pulse Light and topical eflornithine therapy versus Intense Pulse Light therapy alone in the treatment of idiopathic facial hirsutism. METHODOLOGY: A total of 78 patients were included in the study, and were divided into two groups, having 39 patients each. Patients in group A were subjected to combined treatment i.e., topical eflornithine to be applied twice a day and IPL session to be received by patients once a month. Patients in group B were subjected to receive IPL monthly sessions alone. Treatment was continued for 6 months in both groups. After completion of treatment, average number of terminal hair and percentage hair reduction were calculated to see the efficacy. RESULTS: Out of 78 patients, 39 patients were included in group A, and similar number of patients were included in group B. The age of patients ranged from 22-42 years with mean age of 29.59±5.29. Maximum number of patients were in their third decade of life. Mean age in group A was 29.23±5.44, while in group B it was 29.95±5.19. Efficacy in group A was 39(100%) with mean percentage hair reduction of 90.44%, while efficacy in group B was 19 (48.7%) with mean percentage hair reduction of 59.23%, with statistically significant p-value of 0.00. CONCLUSIONS: The combination of intense pulse light and topical eflornithine therapy is more efficacious than intense pulse light therapy alone in the treatment of idiopathic facial hirsutism.

Difluoromethylornithine in cancer: new advances.

Difluoromethylornithine (DFMO; eflornithine) is an irreversible suicide inhibitor of the enzyme ornithine decarboxylase which is involved in polyamine synthesis. Polyamines are important for cell survival, thus DFMO was studied as an anticancer agent and as a chemoprevention agent. DFMO exhibited mainly cytostatic activity and had single agent efficacy as well as activity in combination with other chemotherapeutic drugs for some cancers and leukemias. Herewith, we summarize the current knowledge of the anticancer and chemopreventive properties of DFMO and assess the status of clinical trials.

Androgen excess: Investigations and management.

Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman-Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5α-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response.

Toxicogenomic Effects in Rat Blood Leukocytes and Chemoprophylaxis of Radiation-Induced Carcinogenesis.

Toxicogenomic parameters were studied in the blood of female rats after exposure to ionizing γ-radiation in a dose of 4 Gy and chemoprophylaxis with α-difluoromethylornithine, eleutherococcus or leuzea extracts, which were used in animals with morphological manifestations of tumor growth under conditions of radiation-induced carcinogenesis. Life-time evaluation of toxicogenomic effects was carried out by express method for measurements of blood nucleotid DNA - fluorescent indication. The level of hyperaneu/polyploidy increased in the blood leukocytes of control rats 30 days after radiation exposure. A significant decrease of genotoxicity as a result of drug treatment in comparison with the number and multiplicity of tumors in irradiated animals was found only in the endocrine and reproductive organs of rats treated by eleutherococcus extract.

Dermatologic care of the transgender patient.

Literature is limited regarding the medical and cosmetic dermatologic issues pertinent to transgender patients and the reasons why 19 transgender individuals seek care from dermatologists. Clinical management of this population has historically been limited to 20 mental health providers, endocrinologists, and select surgeons with expertise in sex reassignment surgery. The impact of hormonal 21 therapy on transgender skin has been well documented in endocrinology journals, but is underrepresented in dermatology 22 literature. Hormonal therapy leads to drastic skin alterations, impacting sebum production, hair growth, and acne, all of which may 23 become a dermatologic concern for the transgender patient. Dermatologists may also be consulted regarding issues such as 24 permanent hair removal, androgenic alopecia, or scar revision following breast reduction surgery or genital reassignment surgery. 25 The purpose of this review is to provide relevant information for use by all dermatology providers who care for transgender 26 patients or patients undergoing transition.

Hirsutism: an evidence-based treatment update.

BACKGROUND: Hirsutism has a relatively high prevalence among women. Depending upon societal and ethnic norms, it can cause significant psychosocial distress. Importantly, hirsutism may be associated with underlying disorders and co-morbidities. Hirsutism should not simply be looked upon as an issue of cosmesis. Patients require appropriate evaluation so that underlying etiologies and associated sequelae are recognized and managed. Treatment of hirsutism often requires a multidisciplinary approach, and a variety of physical or pharmacologic modalities can be employed. Efficacy of these therapies is varied and depends, among other things, upon patient factors including the underlying etiology, hormonal drive, and local tissue sensitivity to androgens. OBJECTIVE: The objective of this paper is to review and summarize current evidence evaluating the efficacy of various treatment modalities for hirsutism in premenopausal women. METHODS: Online databases were searched to identify all relevant prior systematic reviews and meta-analyses as well as recently published (2012-present) randomized controlled trials (RCTs) on hirsutism treatment. RESULTS: Four recently published RCTs met criteria for inclusion in our review. In addition, one meta-analysis and one systematic review/treatment guideline were identified in the recent literature. Physical modalities and oral contraceptive pills (OCPs) remain first-line treatments. Evidence supports the use of electrolysis for permanent hair removal in localized areas and lasers (particularly alexandrite and diode lasers) for permanent hair reduction. Topical eflornithine can be used as monotherapy for mild hirsutism and as an adjunct therapy with lasers or pharmacotherapy in more severe cases. Combined OCPs as a class are superior to placebo; however, antiandrogenic and low-dose neutral OCPs may be slightly more efficacious in improving hirsutism compared with other types of OCPs. Antiandrogens are indicated for moderate to severe hirsutism, with spironolactone being the first-line antiandrogen and finasteride and cyproterone acetate being second-line antiandrogens. Due to its risk for hepatotoxicity, flutamide is not considered a first-line therapy. If used, the lowest effective dose should be administered with careful monitoring of liver enzymes. Monotherapy with an insulin sensitizer does not significantly improve hirsutism. While insulin sensitizers improve important metabolic and endocrine aberrations in polycystic ovary syndrome, they are not recommended when hirsutism is the sole indication for use. Lifestyle modification counseling is recommended. Gonadotropin-releasing hormone analogs and glucocorticoids are only recommended in specific circumstances. Additional therapies without sufficient supportive evidence of efficacy are ovarian surgery, statins (HMG-CoA reductase inhibitors), and vitamin D supplementation. LIMITATIONS: In general, most therapies garner recommendations that are weak (where the estimates of benefits versus risks of therapy are either closely balanced or uncertain) and are based on low- to moderate-quality evidence. CONCLUSIONS: Risks and benefits of treatment must be carefully considered and discussed with the patient. Expectations for efficacy should be appropriately set. A minimum of 6 months is required to see benefit from pharmacotherapy and lifelong treatment is often necessary for sustained benefit.

Drug discovery and human African trypanosomiasis: a disease less neglected?

Human African trypanosomiasis (HAT) has been neglected for a long time. The most recent drug to treat this disease, eflornithine, was approved by the US FDA in 2000. Current treatments exhibit numerous problematic side effects and are often ineffective against the debilitating CNS resident stage of the disease. Fortunately, several partnerships and initiatives have been formed over the last 20 years in an effort to eradicate HAT, along with a number of other neglected diseases. This has led to an increasing number of foundations and research institutions that are currently working on the development of new drugs for HAT and tools with which to diagnose and treat patients. New biochemical pathways as therapeutic targets are emerging, accompanied by increasing numbers of new antitrypanosomal compound classes. The future looks promising that this collaborative approach will facilitate eagerly awaited breakthroughs in the treatment of HAT.

[Pharmaco and diet based prostate cancer prevention]. / Pharmaco-prévention et nutri-prévention des cancers de la prostate.

In 2010, in France, 8,790 men died from prostate cancer despite a low and decreasing mortality rate. The individual risk/benefit ratio of prostate cancer screening is the focus of controversy and currently not in favor of a systematic screening program. Therefore, only prevention could reduce incidence, side effects of treatment and related mortality. Interestingly, prostate cancer prevention is also a field of controversy mainly about 5-alpha-reductase inhibitors. However, it could be expected that pharmaco- or diet-based prevention will be a huge tool for cancer control, even more for prostate cancer burden. This review comprehensively analyses which molecules or compounds could be used in preventive trials. With regard to pharmaco-prevention, three different kinds of drugs could be identified. First drugs, which aim at mainly or even solely reduce prostate cancer risk such as 5-alpha-reductase inhibitors and selective estrogen receptor modulators. Drugs, which aim at wider preventive impact such as: nonsteroidal anti-inflammatory drugs or difluoromethylornithine. Lastly, drugs for which reducing prostate cancer incidence is merely a side effect such as statins, metformin or histones desacetylase inhibitors. With regard to diet-based prevention, two main approaches could be identified: aliments and nutriments, on one hand, and vitamin and minerals, on the other. Interestingly if compounds reach experimental plausibility, natural foods or even global diet seem to have a higher impact. Lastly, besides assessment of efficacy, effectiveness required the critical step of compliance, which might actually be the weakest link of the prevention chain.

[Pseudofolliculitis barbae]. / Pseudofoliculitis de la barba.

Pseudofolliculitis barbae is a chronic, irritating, and potentially disfiguring condition that develops as a result of attempts to eliminate hair from the beard area, usually by shaving. It is difficult to determine the incidence of the disorder, but some studies report that it affects up to 1 of every 5 caucasian individuals and that it is much more common in black persons. Clinically it is characterized by the appearance of inflammatory papules and pustules. Once pseudofolliculitis has become established, treatment consists of avoiding shaving and the use of medical treatment similar to that used in acne. However, the long-term result is much more dependent on prevention through a correct shaving technique. In severe cases or when a definitive solution is sought, the treatment of choice is photodepilation.

Nutrition and colon cancer prevention.

PURPOSE OF REVIEW: In spite of improvements in care of colon cancer patients, prevention may enable potential patients to avoid cancer therapy. Although screening is direct and effective, dietary modification or low-risk chemopreventive agents might prevent colon cancer development. In this article, we review recent developments in colon cancer prevention, emphasizing nutrition. RECENT FINDINGS: Epidemiologic findings continue to suggest that diet is related to colon cancer risk. These findings, although, are inconsistent enough to render dietary recommendations premature. An exciting recent discovery is that the combination of diflouromethylornithine and sulindac substantially decreases adenomatous polyp recurrence. Reliance upon clinical trials continues to grow as a means of testing prevention strategies. SUMMARY: Prevention remains an important goal for reducing the burden of colon cancer. Screening has an important role, although it will probably not eliminate all colon cancer. Nutritional modification remains potentially valuable, although research has not yet identified the objects of nutritional intervention. NSAIDs hold promise as chemopreventive agents.

A randomized bilateral vehicle-controlled study of eflornithine cream combined with laser treatment versus laser treatment alone for facial hirsutism in women.

BACKGROUND AND OBJECTIVE: Although there are a multitude of therapeutic modalities for removing unwanted facial hair in women, there is very little information on using the newer medical treatment approaches in combination. This study was designed to determine whether topical eflornithine can enhance the efficacy of laser hair removal. DESIGN: This was a randomized, double-blind, placebo-controlled, right-left comparison study of eflornithine cream combined with laser treatment versus laser alone for treating unwanted hair on the upper lip in women. All subjects underwent treatment to the entire upper lip with a long pulse alexandrite laser (10-40 ms pulse duration) at fluences of 7 to 40 J/cm(2). Laser treatments were performed every 4 weeks for up to 6 sessions. Each patient also applied either eflornithine or placebo cream twice daily to each side of the upper lip in a double-blinded manner. Subjects were evaluated for safety by recording adverse events and for efficacy via (1) investigator global scoring, (2) patient self assessment, and (3) hair count analysis. RESULTS: Both treatment modalities were well tolerated by the 31 evaluable patients. All 3 outcome measures showed significantly better results in favor of eflornithine plus laser versus laser treatment alone. At the end of the study, complete or almost complete hair removal was achieved in 29 of 31 (93.5%) of the eflornithine-laser-treated sites versus 21 of 31 (67.9%) for the placebo cream-laser-treated sites (P = .021, McNemar test). Statistically significant differences in favor of eflornithine were likewise demonstrated at the final assessment through blinded patient grading (13/31 patients [41.9%] thought that the eflornithine was superior to placebo, P = .029, Poisson regression) and hair count analysis (P < .01, paired t test). LIMITATIONS: This is a single-center study that did not determine whether the differences noted above last beyond 6 months. CONCLUSIONS: On the basis of both investigator and patient assessments and hair count analysis, we have demonstrated that the addition of eflornithine to laser hair removal results in a more rapid and complete reduction of unwanted facial hair in women when the combination is used for up to 6 months.

Eflornithine cream combined with laser therapy in the management of unwanted facial hair growth in women: a randomized trial.

BACKGROUND: Eflornithine cream is approved for the reduction of unwanted facial hair in women. The mechanism of action for eflornithine is reduction in follicular cell growth rate, while laser photoepilation heats hair and adjacent tissues to suspend growth. OBJECTIVE: The objective was to assess the efficacy and safety of eflornithine or vehicle with laser therapy in the treatment of unwanted facial hair in women. METHODS: Subjects were randomized to treatment with eflornithine on one side of the face and vehicle on the contralateral side for 34 weeks. Subjects received Nd:YAG or alexandrite laser therapy to both sides of the face at Weeks 2 and 10. Blinded evaluations included left to right comparisons and appearance relative to baseline. RESULTS: Fifty-four women completed the trial. From Weeks 6 through 22, eflornithine-treated sides showed significant reduction in hair growth. By Week 34, no significant differences were seen. Subject grading showed significant and persistent hair reduction through Week 34 for eflornithine-treated sides. The safety profile for combination therapy is similar to eflornithine alone. CONCLUSION: Eflornithine is safely used in conjunction with laser hair removal treatments and promotes more rapid hair removal when combined with laser treatment. Patients demonstrate a clear preference for treatment with laser and eflornithine.

New dimensions in Hirsutism.

The following is a review of a satellite symposium held at the British Medical Laser Association Meeting, in November 2005. Prof. V.A. Randall gave a comprehensive overview of hormones and hair growth, followed by an in-depth discussion of hirsutism, the therapeutic options, treatment and trends, by Dr. S. Lanigan. Dr. I. Hamzavi concluded the symposium with a presentation of the latest work on eflornithine in combination with laser hair removal. Data were reproduced with the speakers' permission.

Excess salt and pepper hair treated with a combination of laser hair removal and topical eflornithine HCl.

A common problem among aging women, salt and pepper facial hair poses a significant psychosocial impact as well as a challenge for treatment. Various laser therapies or topical eflornithine HCl 13.9% cream are commonly used to reduce the rate of hair growth. We report a case of a woman with salt and pepper hair in the beard distribution. A combination of laser hair removal with concurrent use of topical eflornithine was used in the treatment.

Treatment of hirsutism and acne in hyperandrogenism.

Hirsutism and acne are common and highly distressing complaints in women with polycystic ovary syndrome (PCOS). Drugs are only partially effective on terminalized hairs, and removal of these hairs is usually required. Therefore, management of hirsutism is generally based upon a dual approach: a pharmacological therapy to reduce androgen secretion and/or androgen action, and removal of terminal hair already present. Ovarian suppression of androgen secretion with oral contraceptives is widely used in these women, but its efficacy appears limited. The most effective medical therapy for hirsutism is by anti-androgen drugs. Electrolysis and laser photothermolysis are considered the most effective cosmetic procedures, although the effects of these methods should not be considered permanent. Acne may be treated with different tools, according to the severity of the condition and other characteristics of the patient. These tools include topical and systemic retinoids and antibiotics, topical antibacterial agents, androgen suppression by oral contraceptives, and anti-androgen drugs.

Colorectal cancer prevention: is an ounce of prevention worth a pound of cure?

Colorectal cancer (CRC) is among the most common human malignancies and remains a leading cause of cancer-related morbidity and mortality. Colorectal carcinogenesis is a multistep process characterized by molecular and cellular alterations that result in an identifiable precursor lesion, ie, the adenomatous polyp. The transition from normal mucosa to adenoma and its subsequent progression to carcinoma are protracted events that offer opportunities for preventive interventions. Suppression or reversal of the carcinogenic process in the colorectum with nonpharmacologic or pharmacologic agents, ie, chemoprevention, is an area of considerable research interest and activity. Interest in this field derives from multiple epidemiologic studies showing that regular and continued use of nonsteroidal anti-inflammatory drugs (NSAIDs), predominantly aspirin, is associated with significant reductions in both colorectal adenoma and carcinoma incidence. NSAIDs were first shown to be effective in patients with familial adenomatous polyposis (FAP). Subsequent randomized trials in FAP demonstrated that sulindac and the selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, can significantly regress existing adenomas, and resulted in Food and Drug Administration (FDA) approval of celecoxib for adjunctive management of these patients. Based on the aforementioned data, aspirin and coxibs have been or are currently being evaluated for the prevention of sporadic adenoma recurrence in high-risk patient populations. Evidence indicates that aspirin can reduce adenoma recurrence rates in patients with prior colorectal neoplasia; however, questions remain, including the optimal dosage, timing of initiation and duration of treatment, and clinical benefit versus potential harm to patients. These same issues apply to the nonpharmacologic agents such as calcium, folic acid, and selenium given as dietary supplements. Apart from aspirin, calcium carbonate is the only other agent that has been shown to modestly reduce sporadic adenoma recurrence rates in a randomized trial. Folate and selenium are being actively studied based on provocative preclinical data. In addition to demonstrating efficacy, chemopreventive agents must also be safe for long-term use, be well accepted by patients, and be cost-effective. In this review, the current status of CRC chemoprevention will be discussed, including the available evidence for selected pharmacologic and nonpharmacologic agents, particularly among high-risk populations.