The future of frozen-thawed embryo transfer in hormone replacement therapy cycles.

PURPOSE OF REVIEW: This review focuses on the efficacy of letrozole stimulated frozen-thawed embryo transfer (FET) compared to hormone replacement therapy (HRT) FET in women with polycystic ovarian syndrome (PCOS) and/or oligo-anovulation. Further, obstetric and perinatal risks in HRT FET are summarized. RECENT FINDINGS: The presence of a corpus luteum seems to reduce the risk of pregnancy-related hypertension and preeclampsia after FET. As a natural cycle (NC) FET is not an option for women with oligo-/amenorrhea these women may benefit from FET with mild stimulation compared to HRT FET. The intention of mild stimulation in anovulatory women is to induce (mono) ovulation to mimic the endocrine profiles of the natural cycle and the early pregnancy after natural conception. Mild stimulation by letrozole is patient friendly and cheap compared to gonadotropin stimulated FET and has been increasingly used in recent years. Although the quality of evidence is low, the pregnancy outcomes after letrozole FET seems similar or even better compared to HRT FET in women with PCOS and/or oligo-anovulation. SUMMARY: Natural and modified NC FET should be used whenever possible to mitigate adverse obstetric and perinatal outcomes after HRT FET. For anovulatory women, whenever ovulation can be induced, we advocate the use of mild stimulation FET to create a corpus luteum awaiting results from RCTs limited to oligo-anovulatory women.

Effects of transdermal estrogen therapy on satellite cell number and molecular markers for muscle hypertrophy in response to resistance training in early postmenopausal women.

PURPOSE: To investigate the effects of resistance training with or without transdermal estrogen therapy (ET) on satellite cell (SC) number and molecular markers for muscle hypertrophy in early postmenopausal women. METHODS: Using a double-blinded randomized controlled design, we allocated healthy, untrained postmenopausal women to perform 12 weeks of resistance training with placebo (PLC, n = 16) or ET (n = 15). Muscle biopsies obtained before and after the intervention, and two hours after the last training session were analyzed for fiber type, SC number and molecular markers for muscle hypertrophy and degradation (real-time PCR, western blotting). RESULTS: The analysis of SCs per Type I fiber showed a time x treatment interaction caused by a 47% decrease in PLC, and a 26% increase after ET after the training period. Also, SCs per Type II fiber area was lower after the intervention driven by a 57% decrease in PLC. Most molecular markers changed similarly in the two groups. CONCLUSION: A decline in SC per muscle fiber was observed after the 12-week training period in postmenopausal women, which was counteracted when combined with use of transdermal ET. CLINICAL TRIAL REGISTRATION NUMBER: nct03020953.

Muscle Performance during the Menstrual Cycle Correlates with Psychological Well-Being, but Not Fluctuations in Sex Hormones.

PURPOSE: We aimed to study variations in strength and power performance during the menstrual cycle (MC) in eumenorrheic young women and during the pill cycle in oral contraceptives (OC) users. METHODS: Forty healthy, normal-weight women between 18 and 35 yr (n = 30 eumenorrheic women; n = 10 OC users) completed this prospective cohort study. Seven to nine times during the MC/pill-cycle, the participants completed a physical performance test series, a questionnaire about psychological well-being, blood sampling, and determination of body mass. The physical tests included isometric handgrip strength, elbow flexor strength, countermovement jump (CMJ) height, and a 10-s Wingate bike test. RESULTS: No direct correlation was observed between the variations in sex hormones and physical performance parameters. However, positive correlations were observed between physical performance outcomes and self-reported motivation, perception of own physical performance level, pleasure level, and arousal level. CMJ was 6% lower in the late luteal phase (LL) compared with the midluteal phase (ML) (P = 0.04). Wingate peak power was 3% lower in early follicular (EF) compared with the ML (P = 0.04). Furthermore, Wingate average power was 2%-5% lower in LL compared with all other MC phases. In line with these observations, physical pain was higher in EF and LL, and the pleasure level was lower in EF compared with the other MC phases. In OC users, we observed no variation in performance and self-reported parameters between the placebo-pill phase and the OC-pill phase. CONCLUSIONS: Impairments in CMJ and Wingate performance were observed at the end and start of MC compared with other MC phases, which were associated with lower psychological well-being, but not the sex hormone fluctuations.

Women With Turner Syndrome Are Both Estrogen and Androgen Deficient: The Impact of Hormone Replacement Therapy.

CONTEXT: Women with Turner syndrome (TS) suffer from hypergonadotropic hypogonadism, causing a deficit in gonadal hormone secretion. As a consequence, these women are treated with estrogen from the age of 12 years, and later in combination with progesterone. However, androgens have been given less attention. OBJECTIVE: To assess sex hormone levels in women with TS, both those treated and those nontreated with hormone replacement therapy (HRT), and investigate the impact of HRT on sex hormone levels. METHODS: At Aarhus University Hospital, 99 women with TS were followed 3 times from August 2003 to February 2010. Seventeen were lost during follow-up. Control group 1 consisted of 68 healthy age-matched control women seen once during this period. Control group 2 consisted of 28 young, eumenorrheic women sampled 9 times throughout the same menstrual cycle. Serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17ß-estradiol, estrone sulfate, DHEAS, testosterone, free androgen index, androstenedione, 17-OH progesterone, and sex hormone-binding globulin (SHBG) were analyzed. RESULTS: All androgens, 17-OH progesterone, and sex hormone-binding globulin (SHBG) were 30% to 50% lower in TS compared with controls (P < 0.01). FSH, LH, and estrone sulfate were more than doubled in women with TS compared with controls (P < 0.02). Using principal component analysis, we describe a positive correlation between women with TS receiving HRT, elevated levels of SHBG, and decreased levels of androgens. CONCLUSION: The sex hormone profile in TS reveals a picture of androgen deficiency, aggravated further by HRT. Conventional HRT does not normalize estradiol levels in TS.

Fluctuations in Metabolites and Bone Markers Across the Menstrual Cycle in Eumenorrheic Women and Oral Contraceptive Users.

CONTEXT: Little is known about changes in circulating metabolites during the menstrual cycle and how use of oral contraceptives (OCs) affects these changes. OBJECTIVES: To study fluctuations in circulating metabolite and bone marker levels during the menstrual/pill cycle in eumenorrheic women and OC users. METHODS: Plasma samples were collected from 28 eumenorrheic women and 10 OC users at 7 to 9 time points across a menstrual/pill cycle. Longitudinal and cross-sectional analyses were performed to examine the cycle- and OC-induced variations in the plasma metabolite and bone turnover marker levels. RESULTS: In eumenorrheic women, plasma levels of alanine, glutamine, threonine, and tyrosine varied significantly across the menstrual cycle, and all dropped to the lowest level around day 21 of the menstrual cycle. These amino acid concentrations were negatively correlated with fluctuations in progesterone and/or estrogen levels. A between-group analysis showed that plasma levels of alanine, glutamine, glycine, proline, and tyrosine were lower in OC users than in nonusers. Concomitantly, plasma C-terminal telopeptide of type I collagen (CTX) and N-terminal propeptide of type I procollagen (PINP) levels were lower in OC users. Intriguingly, when all data were pooled, variations in CTX and PINP levels were positively correlated with fluctuations in proline and glycine concentrations (r > 0.5 or 0.3 < r < 0.5, P < 0.05). CONCLUSIONS: The menstrual cycle and the use of OCs alter plasma levels of metabolites and bone turnover markers in young women. While the impact of these findings remains to be established, the lower glycine level among OC users and the accompanying lower CTX level supports that the use of OCs lowers collagen turnover in young women and may thereby have long-term implications for bone health among OC users.

Estrogen modulates metabolic risk profile after resistance training in early postmenopausal women: a randomized controlled trial.

OBJECTIVE: Women experience an unhealthy change in metabolic risk profile at menopause. The purpose of the present study was to determine effects of resistance training with or without transdermal estrogen therapy (ET) on adipose tissue mass and metabolic risk profile in early postmenopausal women. METHODS: A double-blinded randomized controlled trial, where healthy, untrained postmenopausal women were allocated to supervised resistance training with placebo (PLC, n = 16) or transdermal ET (n = 15) for 12 weeks. Endpoints with prespecified hypotheses were the change in total fat mass (FM) (main endpoint) and the change in visceral FM (secondary endpoint) from before to after the intervention. Additionally, prespecified endpoints of body composition, metabolic health-related blood markers, fat%, fat cell size, and lipogenic markers in subcutaneous adipose tissue (SAT) from abdominal and femoral region were explored. RESULTS: Compared with the ET group, the PLC group experienced a greater reduction (time × treatment interaction P < 0.05) in total FM (PLC vs ET: -5.6% vs -1.1%) and visceral FM (-18.6% vs -6.8%), and femoral SAT (-5.6% vs 1.0%), but not abdominal SAT mass (-8.5% vs -2.8%, P = 0.15).The ET group improved their metabolic blood profile by reduced low-density lipoprotein, glucose and hemoglobin A1c compared with PLC (time × treatment interaction P < 0.05). The intervention induced changes in lipolytic markers of abdominal SAT, whereas no changes were detected in femoral SAT. CONCLUSION: Use of transdermal ET reduced adipose tissue loss, but improved metabolic blood markers when combined with 12 weeks of progressive resistance training in early postmenopausal women.

Transdermal Estrogen Therapy Improves Gains in Skeletal Muscle Mass After 12 Weeks of Resistance Training in Early Postmenopausal Women.

CONTEXT: Women show an accelerated loss of muscle mass around menopause, possibly related to the decline in estrogen. Furthermore, the anabolic response to resistance exercise seems to be hampered in postmenopausal women. OBJECTIVE: We aimed to test the hypothesis that transdermal estrogen therapy (ET) amplifies the skeletal muscle response to resistance training in early postmenopausal women. DESIGN: A double-blinded randomized controlled study. SETTING: Department of Public Health, Aarhus University, Denmark. PARTICIPANTS: Thirty-one healthy, untrained postmenopausal women no more than 5 years past menopause. INTERVENTIONS: Supervised resistance training with placebo (PLC, n = 16) or transdermal ET (n = 15) for 12 weeks. MAIN OUTCOME MEASURES: The primary outcome parameter was a cross-sectional area of quadriceps femoris measured by magnetic resonance imaging, and secondary parameters were fat-free mass (dual-energy X-ray absorptiometry), muscle strength, and functional tests. RESULTS: The increase in muscle cross-sectional area was significantly greater in the ET group (7.9%) compared with the PLC group (3.9%) (p < 0.05). Similarly, the increase in whole-body fat-free mass was greater in the ET group (5.5%) than in the PLC group (2.9%) (p < 0.05). Handgrip strength increased in ET (p < 0.05) but did not change in the PLC group. Muscle strength parameters, jumping height, and finger strength were all improved after the training period with no difference between groups. CONCLUSION: The use of transdermal ET enhanced the increase in muscle mass in response to 12 weeks of progressive resistance training in early postmenopausal women.