Efficacy of progestin-only treatment for the management of menopausal symptoms: a systematic review.

IMPORTANCE: Menopause is associated with bothersome symptoms for many women, including mood changes, hot flushes, sleep problems, and fatigue. Progesterone is commonly prescribed in combination with estrogen therapy. Although monotherapy with progestins has been used as treatment of menopausal symptoms in women with contraindications to estrogens, the optimal route, and dosage of progestin monotherapy has not been established. OBJECTIVE: To assess whether progestin as a standalone treatment is effective for treating vasomotor and mood symptoms associated with menopause. EVIDENCE REVIEW: We conducted a systematic review using PubMed and Embase databases from January 1980 to January 2020. We included randomized controlled trials (RCTs) that investigated different forms of progestin for the treatment of vasomotor or mood symptoms associated with menopause. FINDINGS: A systematic search of 892 studies identified seven RCTs involving a total of 601 patients. The available literature was heterogeneous in terms of formulation and dose of progesterone; administration ranged from 5 to 60 mg of transdermal progesterone, 10 to 20 mg oral medroxyprogesterone acetate, and 300 mg of oral micronized progesterone. Duration of treatment also differed between studies, ranging from 21 days to 12 months (median: 12 wks). Three of seven RCTs reported that progestin therapy led to an improvement of vasomotor symptoms (VMS) in postmenopausal women. The largest study administering oral progestin using 300 mg micronized progesterone reported a 58.9% improvement in VMS (vs 23.5% in placebo group, n = 133), whereas the largest study using transdermal progesterone reported no improvement (n = 230). No study reported an improvement of mood symptoms. Side effects, such as headaches and vaginal bleeding, were significant in five of seven RCTs and led to discontinuation of treatment in 6% to 21% of patients. CONCLUSIONS AND RELEVANCE: A beneficial effect was reported in some trials with the transdermal route at longer duration and with oral treatment at higher doses for VMS for progesterone-only therapy. This report may help to inform future studies of progestin-only therapy for the treatment of menopausal symptoms.

Video Summary:http://links.lww.com/MENO/A671.

Immediate and Short-Term Effects of Short- and Long-Duration Isometric Contractions in Patellar Tendinopathy.

OBJECTIVES: Isometric muscle contractions are used in the management of patellar tendinopathy to manage pain and improve function. Little is known about whether long- or short-duration contractions are optimal to improve pain. This study examined the immediate and short-term (4 weeks) effects of long- and short-duration isometric contraction on patellar tendon pain, and tendon adaptation. DESIGN: Repeated measures within groups. SETTING: Clinical primary care. PATIENTS: Participants (n = 16, males) with patellar tendinopathy. INTERVENTION: Short-duration (24 sets of 10 seconds) or long-duration (6 sets of 40 seconds) isometric knee extension loading (85% maximal voluntary contraction), for 4 weeks. MAIN OUTCOME MEASURE: Immediate change in pain with single-leg decline squat (SLDS) and hop, as well as change in pain and tendon adaptation [within-session anterior-posterior (AP) strain] were assessed over 4 weeks. RESULTS: Pain was significantly reduced after isometric loading on both SLDS (P < 0.01) and hop tests (P < 0.01). Pain and quadriceps function improved over the 4 weeks (P < 0.05). There was significant AP strain at each measurement occasion (P < 0.01). Although transverse strain increased across the training period from ∼14% to 22%, this was not significant (P = 0.08). CONCLUSIONS: This is the first study to show that short-duration isometric contractions are as effective as longer duration contractions for relieving patellar tendon pain when total time under tension is equalized. This finding provides clinicians with greater options in prescription of isometric loading and may be particularly useful among patients who do not tolerate longer duration contractions. The trend for tendon adaptation over the short 4-week study period warrants further investigation.

Heme sensing in Bacillus thuringiensis: a supplementary HssRS-regulated heme resistance system.

Several Gram-positive pathogens scavenge host-derived heme to satisfy their nutritional iron requirement. However, heme is a toxic molecule capable of damaging the bacterial cell. Gram-positive pathogens within the phylum Firmicutes overcome heme toxicity by sensing heme through HssRS, a two-component system that regulates the heme detoxification transporter HrtAB. Here we show that heme sensing by HssRS and heme detoxification by HrtAB occur in the insect pathogen Bacillus thuringiensis We find that in B. thuringiensis, HssRS directly regulates an operon, hrmXY, encoding hypothetical membrane proteins that are not found in other Firmicutes with characterized HssRS and HrtAB systems. This novel HssRS-regulated operon or its orthologs BMB171_c3178 and BMB171_c3330 are required for maximal heme resistance. Furthermore, the activity of HrmXY is not dependent on expression of HrtAB. These results suggest that B. thuringiensis senses heme through HssRS and induces expression of separate membrane-localized systems capable of overcoming different aspects of heme toxicity.