The following represent additions to UpToDate since the last version that were considered by the authors and editors to be of particular interest. The new material described below represents a small subset of the updating that has been performed, since approximately 40 percent of the topic reviews are updated during each four-month cycle.

ADRENAL

DHEA for vaginal atrophy — Intravaginal DHEA administration may be a novel therapy for postmenopausal women with atrophic vaginitis and sexual dysfunction. In a trial of postmenopausal women with symptomatic vaginal atrophy, 12 weeks of intravaginal DHEA administration corrected signs and symptoms of atrophy, and, when compared to placebo, appeared to improve some measures of sexual function. No significant increases in serum DHEA or estrogen concentrations were seen. This agent is not commercially available. Further study is necessary to know if this will be a safe and effective therapy. (See "Dehydroepiandrosterone and its sulfate", section on 'Vaginal atrophy'.)

REPRODUCTION

Endocrine treatment of transsexual individuals — The Endocrine Society has published evidence-based clinical practice guidelines, (using the GRADE system) on the diagnosis and treatment of transsexualism in adolescents and adults [1]. The general endocrine approach is to suppress the endogenous hormones of the individual's biologic sex, and then administer exogenous hormones of the desired gender, maintaining hormone levels within the normal range for that gender. This is followed by surgical reassignment in appropriate candidates. (See "Treatment of transsexualism", section on 'Endocrine Society Guidelines'.)

Cytotoxic agents and testicular damage — Ifosfamide-based regimens for childhood cancer appear to result in less testicular damage than cyclophosphamide-based regimens [2]. (See "Effects of cytotoxic agents on gonadal function in adult men".)

DIABETES

DPP-IV inhibitors — Saxagliptin, a new DPP-IV inhibitor that reduces hemoglobin A1C by approximately 0.5 percentage points, can be used as initial pharmacologic therapy for the treatment of type 2 diabetes or as a second agent in those who do not respond to a single agent, such as a sulfonylurea, metformin, or a thiazolidinedione [3,4]. (See "GLP-1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Saxagliptin'.)

There have been 88 postmarketing case reports of acute pancreatitis in patients using sitagliptin [5]. Pancreatitis should be considered in patients with persistent severe abdominal pain (with or without nausea), and sitagliptin (or sitagliptin/metformin) should be discontinued in such patients. (See "GLP-1-based therapies for the treatment of type 2 diabetes mellitus", section on 'DPP-IV inhibitors'.)

Insulin glargine — Data regarding use of insulin analogs and risk of cancer are conflicting for insulin glargine [6-10]. Until more data are available, there is insufficient evidence to make a recommendation against glargine. (See "General principles of insulin therapy in diabetes mellitus", section on 'Human versus analogs'.)

In a five-year trial in over 1000 patients with type 2 diabetes previously treated with oral hypoglycemic agents, insulin, or both, there was no difference in the risk of retinopathy progression (defined as an increase in three steps or more on the early treatment of diabetic retinopathy study [ETDRS] scale) in patients randomly assigned to twice daily NPH versus once daily glargine [11]. (See "General principles of insulin therapy in diabetes mellitus", section on 'Human versus analogs'.)

Mediterranean diet — In a four-year trial of a low carbohydrate Mediterranean-style diet (≤50 percent complex carbohydrates, ≥30 percent mono and polyunsaturated fat) versus a low fat (<30 percent) diet in 215 overweight patients with newly diagnosed type 2 diabetes, patients randomly assigned to the Mediterranean diet were significantly less likely to require antihyperglycemic drugs (44 versus 70 percent) [12]. (See "Nutritional considerations in type 2 diabetes mellitus", section on 'Nutritional content'.)

OSTEOPOROSIS

Vertebroplasty — In two short-term, blinded trials comparing vertebroplasty with a sham procedure in patients with osteoporotic vertebral compression fractures, there was no immediate or delayed benefit of vertebroplasty for the reduction of pain [13,14]. (See "Clinical manifestations and treatment of osteoporotic thoracolumbar vertebral compression fractures", section on 'Vertebroplasty and kyphoplasty'.)

Denosumab — In the FREEDOM trial (7868 postmenopausal women with BMD T-scores between -2.5 and -4.0 at the LS or total hip), denosumab compared with placebo significantly reduced the incidence of new vertebral (2.3 versus 7.2 percent), hip (0.7 versus 1.2 percent), and nonvertebral fractures (6.0 versus 8.5 percent) [15]. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Denosumab'.)

Vitamin K — In a trial of vitamin K (1000 micrograms phylloquinone or 45 mg menatetrenone daily) versus placebo in nonosteoporotic postmenopausal women receiving calcium and vitamin D supplements, vitamin K did not have any effect on BMD [16]. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Vitamin K'.)

THYROID

Treatment guidelines for medullary thyroid cancer — The American Thyroid Association has published Clinical Guidelines for the management of inherited and sporadic medullary thyroid cancer; the document includes 172 recommendations [17]. (See "Treatment of medullary thyroid cancer".)

PTU hepatoxicity — Due to reports of severe PTU-related liver failure, the American Thyroid Association and the US Food and Drug Administration have published new recommendations (in preliminary form) for PTU use [18,19]. We agree with their recommendations and suggest that PTU NOT be prescribed as the first line drug in children or adults. There are three settings where we still suggest PTU over MMI, including:

• Pregnant women during their first trimester (where the risk of methimazole-associated birth defects might outweigh the risks of PTU)
• Patients with life-threatening thyrotoxicosis or thyroid storm (because of PTU's ability to inhibit peripheral conversion of T4 to T3)
• Patients with adverse reactions to MMI (other than agranulocytosis) who are not candidates for radioiodine or surgery.

We suggest that routine monitoring of liver function not be done, but should be performed if patients develop symptoms suggestive of liver disease. (See "Pharmacology and toxicity of thionamides" and "Diagnosis and treatment of hyperthyroidism during pregnancy".)