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| Hormonal fluctuation during (A) a normal menstrual cycle, (B) while taking an oral contraceptive (OC) containing both estrogen and progesterone, and (C) in the years before and after menopause.
Source publication
Estrogen has a dramatic effect on musculoskeletal function. Beyond the known relationship between estrogen and bone, it directly affects the structure and function of other musculoskeletal tissues such as muscle, tendon, and ligament. In these other musculoskeletal tissues, estrogen improves muscle mass and strength, and increases the collagen cont...
Contexts in source publication
Context 1
... secretion naturally varies in young women, increasing 10-to 100-fold over the menstrual cycle. Beyond estrogen, the menstrual cycle is characterized by significant changes in other important plasma hormones such as follicle stimulating hormone (FSH), luteinizing hormone (LH), and progesterone (Figure 1). 17β-estradiol levels rise from 5 pg/ml at the early follicular phase, to a peak of 200-500 pg/ml just before ovulation. ...
Context 2
... pills typically maintain estradiol levels at ∼25 pg/ml and decrease the ovulatory rise in estrogen ( Mishell et al., 1972). This daily dose of estrogen and or progesterone also eliminates the cyclic rise in LH and FSH ( Figure 1B). In the absence of oral contraceptives, the menstrual cycle will occur from puberty until menopause when menses stop, FSH and LH rise, and plasma estradiol and progesterone concentrations remain constantly low ( Figure 1C). ...
Context 3
... daily dose of estrogen and or progesterone also eliminates the cyclic rise in LH and FSH ( Figure 1B). In the absence of oral contraceptives, the menstrual cycle will occur from puberty until menopause when menses stop, FSH and LH rise, and plasma estradiol and progesterone concentrations remain constantly low ( Figure 1C). ...
Citations
... The exclusive manifestation of this pronounced change in females may possibly generate an impaired equilibrium between neuronal excitation and inhibition in advanced age. Occurring concurrently with an increased risk of osteoporosis (Sözen et al., 2017) and heightened joint stiffness (Chidi-Ogbolu & Baar, 2019;Leblanc et al., 2017), physical function and mobility decrements in females may exceed that of males. ...
Females typically live longer than males but, paradoxically, spend a greater number of later years in poorer health. The neuromuscular system is a critical component of the progression to frailty, and motor unit (MU) characteristics differ by sex in healthy young individuals and may adapt to ageing in a sex‐specific manner due to divergent hormonal profiles. The purpose of this study was to investigate sex differences in vastus lateralis (VL) MU structure and function in early to late elderly humans. Intramuscular electromyography signals from 50 healthy older adults (M/F: 26/24) were collected from VL during standardized submaximal contractions and decomposed to quantify MU characteristics. Muscle size and neuromuscular performance were also measured. Females had higher MU firing rate (FR) than males (P = 0.025), with no difference in MU structure or neuromuscular junction transmission (NMJ) instability. All MU characteristics increased from low‐ to mid‐level contractions (P < 0.05) without sex × level interactions. Females had smaller cross‐sectional area of VL, lower strength and poorer force steadiness (P < 0.05). From early to late elderly, both sexes showed decreased neuromuscular function (P < 0.05) without sex‐specific patterns. Higher VL MUFRs at normalized contraction levels previously observed in young are also apparent in old individuals, with no sex‐based difference of estimates of MU structure or NMJ transmission instability. From early to late elderly, the deterioration of neuromuscular function and MU characteristics did not differ between sexes, yet function was consistently greater in males. These parallel trajectories underscore the lower initial level for older females and may offer insights into identifying critical intervention periods. image
Key points
Females generally exhibit an extended lifespan when compared to males, yet this is accompanied by a poorer healthspan and higher rates of frailty.
In healthy young people, motor unit firing rate (MUFR) at normalized contraction intensities is widely reported to be higher in females than in age‐matched males.
Here we show in 50 people that older females have higher MUFR than older males with little difference in other MU parameters. The trajectory of decline from early to late elderly does not differ between sexes, yet function is consistently lower in females.
These findings highlight distinguishable sex disparities in some MU characteristics and neuromuscular function, and suggest early interventions are needed for females to prevent functional deterioration to reduce the ageing health–sex paradox.
... The predominant theory is that elevated levels of estradiol increase soft tissue laxity and make the ACL more prone to rupture. 6 However, the time of the menstrual cycle when knee joint laxity is greatest does not match the time when ACL injuries are most frequent, 46 suggesting a hormonal influence on injury by factors other than laxity alone. Sex hormones exert pleiotropic effects beyond the reproductive system, 32 which creates the potential for various hormone-mediated injury mechanisms, including altered neural excitability 2,23,45 and specific force of muscle. ...
Background
Anterior cruciate ligament (ACL) injuries often occur when an athlete experiences an unexpected disruption, or perturbation, during sports. ACL injury rates may also be influenced by the menstrual cycle.
Purpose
To determine whether training adaptations to knee control and muscle activity during a perturbed single-leg squatting (SLS) task depend on menstrual cycle phase in female athletes.
Study Design
Controlled laboratory study.
Methods
A total of 21 healthy female collegiate athletes (current or former [<3 years]) who competed in 9 different sports performed an SLS task in which they attempted to match their knee position (user signal) to a target signal. The protocol consisted of a 9-condition pretest, 5 sets of 3 training trials, and a 9-condition posttest. One perturbation was delivered in each condition by altering the resistance of the device. Sagittal knee control (absolute error between the target signal and user signal) was assessed using a potentiometer. Muscle activity during perturbed squat cycles was normalized to maximal activation and to corresponding muscle activity during unperturbed squat cycles (%unperturbed) within the same test condition. Athletes performed the protocol during a distinct menstrual cycle phase (early follicular [EF], late follicular [LF], midluteal [ML]). Two-way mixed analysis of variance was used to determine the effects of the menstrual cycle and training on knee control and muscle activity during task performance. Venous blood was collected for hormonal analysis, and a series of health questionnaires and anthropometric measures were also assessed to determine differences among the menstrual cycle groups.
Results
After training, athletes demonstrated better knee control during the perturbed squat cycles (lower absolute error, P < .001) and greater soleus feedback responses to the perturbation (%unperturbed, P = .035). Better knee control was demonstrated in the ML phase versus the EF phase during unperturbed and perturbed squat cycles ( P < .039 for both). Quadriceps activation was greater in the ML phase compared with the EF and LF phases, both immediately before and after the perturbation ( P < .001 for all).
Conclusion
Athletes learned to improve knee control during the perturbed performance regardless of menstrual cycle phase. The best knee control and greatest quadriceps activation during the perturbed squatting task was found in the ML phase.
Clinical Relevance
These findings may correspond to a lower incidence of ACL injury in the luteal phase and alterations in exercise performance across the menstrual cycle.
... Higher progesterone has also been shown to promote weight gain that is mostly or entirely fat in males and females [15]. Estrogen has been shown to improve muscle mass, strength, and collagen content, yet, in tendons and ligaments, estrogen can decrease stiffness, affecting performance and increasing injury rates [16]. While these hormones clearly influence anabolic pathways and body composition, research examining estrogen and progesterone levels post RET has predominantly been conducted in female cohorts [17,18]. ...
Introduction: Resistance exercise training (RET) can increase muscle mass and strength, and this adaptation is optimized when dietary protein is consumed to enhance muscle protein synthesis. Dairy milk has been endorsed for this purpose; however, allergy and lactose intolerance affect two-thirds of the global population making dairy milk unsuitable for many. Plant-based alternatives such as soy milk have gained popularity and exhibit comparable protein content. However, concerns regarding soy phytoestrogens potentially influencing circulating sex hormones and diminishing the anabolic response to RET have been raised. This study therefore aimed to assess the acute effects of dairy and soy milk consumption on circulating sex hormones (total, free testosterone, free testosterone percentage, total estrogen, progesterone, and sex hormone binding globulin) after RET.
Materials and methods: Six male participants were recruited for a double-blinded, randomized crossover study with either dairy or soy milk provided post RET. Venous samples were collected before and after milk consumption across seven timepoints (0-120 minutes) where circulating sex hormones were analyzed. Two-way ANOVA analyses were applied for repeated measures for each hormone. The area under the curve (AUC) was also calculated between dairy and soy milk. Significance was set at p<0.05.
Results: No significant differences were observed in acute circulating serum for free (p=0.95), % free (p=0.56), and total testosterone (p=0.88), progesterone (p=0.67), or estrogen (p=0.21) between milk conditions. Likewise, no significant differences in AUC were observed between any hormones.
Conclusion: These findings suggest that consumption of dairy milk and soy milk have comparable acute effects on circulating sex hormones following RET. Further investigations with expanded sample sizes are needed to strengthen and broaden these initial findings.
... A late first menstruation delays the production of relaxin and thereby may increase collagenous cross-linking in ligaments and reduce its growth potential. Estrogen, as a last example, increases collagen turnover and decreases the stiffness of tendons and ligaments by inhibiting lysyl oxidase and decreasing cross-linking [90,91]. A lack of estrogen, as a result of late menarche, thus enhances cross-linking and reduces growth potential of tendons and ligaments. ...
Purpose
To describe the physiology of spinal growth in patients with adolescent idiopathic scoliosis (AIS).
Methods
Narrative review of the literature with a focus on mechanisms of growth.
Results
In his landmark publication On Growth and Form, D’Arcy Thompson wrote that the anatomy of an organism reflects the forces it is subjected to. This means that mechanical forces underlie the shape of tissues, organs and organisms, whether healthy or diseased. AIS is called idiopathic because the underlying cause of the deformation is unknown, although many factors are associated. Eventually, however, any deformity is due to mechanical forces. It has long been shown that the typical curvature and rotation of the scoliotic spine could result from vertebrae and intervertebral discs growing faster than the ligaments attached to them. This raises the question why in AIS the ligaments do not keep up with the speed of spinal growth. The spine of an AIS patient deviates from healthy spines in various ways. Growth is later but faster, resulting in higher vertebrae and intervertebral discs. Vertebral bone density is lower, which suggests less spinal compression. This also preserves the notochordal cells and the swelling pressure in the nucleus pulposus. Less spinal compression is due to limited muscular activity, and low muscle mass indeed underlies the lower body mass index (BMI) in AIS patients. Thus, AIS spines grow faster because there is less spinal compression that counteracts the force of growth (Hueter–Volkmann Law). Ligaments consist of collagen fibres that grow by tension, fibrillar sliding and the remodelling of cross-links. Growth and remodelling are enhanced by dynamic loading and by hormones like estrogen. However, they are opposed by static loading.
Conclusion
Increased spinal elongation and reduced ligamental growth result in differential strain and a vicious circle of scoliotic deformation. Recognising the physical and biological cues that contribute to differential growth allows earlier diagnosis of AIS and prevention in children at risk.
... Prevalence of knee osteoarthritis is higher in women as compared to men. Evidence suggests that women's susceptibility to osteoarthritis may be related to increased hormone levels during certain stages of the menstrual cycle which may increase joint laxity, which is associated with joint instability and injury (Chidi-Ogbolu & Baar, 2019;Jin et al., 2017;Shultz et al., 2005). Both joint instability and injury contributes to the development of osteoarthritis. ...
Objective:The alignment of spine-pelvis-lower extremity axis is significantly influenced by knee osteoarthritis. Joint alignment is the main bio-mechanical risk factor for progression of knee osteoarthritis. The purpose of this study was to find out the effect of spinal and lower limb realignment protocol on bilateral medial compartment knee osteoarthritis in postmenopausal women and to compare it with the conventional method of treatment for osteoarthritis of knee.Method: A study sample of 98 post-menopausal subjects having bilateral knee osteoarthritis with medial compartment involvement were selected and equally divided into two groups as the control group and the experimental group. Assessment of pain, knee range of motion, quadriceps and hip abductor strength, and posture for spinal and lower limb malalignment was taken before and after giving the treatment regime to both the groups. Comparison was carried out between the results of the two groups. Results:The results showed how significantly the mal-aligned structures were re-aligned after giving 8 weeks of realignment protocol and how significantly this resulted in better reduction of pain intensity and improvement in knee range of motion and strength of quadriceps and hip abductor muscles in experimental group as compared to the control group. Conclusion:Re-aligning the spinal and lower limb malalignment present in postmenopausal women with bilateral medial compartment knee osteoarthritis results in pain reduction associated with knee joint and improved knee range of motion and strength of quadriceps and hip abductor muscles in these individuals as compared to the ones receiving conventional physiotherapy.
... Although it is not clear that one specific phase may be associated with general injury incidence, evidence suggests a higher probability of certain types of injury in either the ovulatory or luteal phases compared to the menstruation and mid-follicular phase, with variable findings depending on the type and cause of injury (Martínez-Fortuny et al., 2023;Martin et al., 2021). For example, a particularly higher prevalence of non-contact muscle injuries (Barlow et al., 2024) and concussions (La Fountaine et al., 2019) have been reported in the luteal phase; while ACL injuries are reportedly least common in the luteal phase (Herzberg et al., 2017) and most common in the late follicular or ovulatory phases instead (Martin et al., 2021;Chidi-Ogbolu and Baar, 2019). Such effects have been reported in the general population (Balachandar et al., 2017), in mixed recreational and professional contact sports (Martínez-Fortuny et al., 2023) and in professional footballers specifically (Martin et al., 2021), suggesting that competitive level and sporting expertise might not be a protective, nor detrimental, factor. ...
... In sport medicine literature, the most researched injury type in this context are anterior cruciate ligament (ACL) injuries. Some authors have hypothesised that changes in joint laxity and poorer neuromuscular control during ovulation could be driving the observed increase in ACL injuries in this phase (Chidi-Ogbolu and Baar, 2019;Balachandar et al., 2017;Herzberg et al., 2017). However, while knee joint laxity has been substantiated as a significant risk factor for ACL injuries in the general population (Zsidai et al., 2023;Sundemo et al., 2019) and in female athletes (Myer et al., 2008), a direct link between possible cycle-related changes in laxity and injury prevalence has not yet been established (Raj et al., 2023;Dos' Santos et al., 2023;Martínez-Fortuny et al., 2023). ...
... It is therefore likely that the larger baseline musculature of males is subject to experiencing greater absolute hypertrophy than that of females, despite females having a similar potential to induce muscle hypertrophy as males when considering relative increases from baseline muscle size. Supportive of our findings is research highlighting i) the anabolic properties of estradiol that may contribute to muscle hypertrophy [48][49][50], ii) the positive association between androgen receptor content with muscle hypertrophy [51], and iii) similarities in post-exercise protein synthesis and molecular signalling between sexes that triggers muscle hypertrophy [52,53]. Taken as a whole, our data suggest RT is likely to induce greater absolute increases in muscle size for males versus females, while similar percentage increases in muscle size from baseline suggest comparable muscle hypertrophic potential between males and females following RT. ...
Muscle hypertrophy may be influenced by biological differences between males and females. This systematic review with meta-analysis investigated absolute and relative changes in muscle size following resistance training (RT) between males and females and whether key variables (i.e., assessment of muscle size, individual characteristics, and RT characteristics) moderate the results. Studies were included if male and female participants were apparently healthy (18-50 years old) adults of any RT experience that completed the same RT intervention, and a valid measure of pre- to post-intervention changes in muscle size was included. Out of 2199 retrieved studies, a total of 27 studies were included in the statistical analysis. Bayesian methods were used to estimate an effect size (ES) and probability of direction (pd) for each outcome. Superior increases in absolute muscle size were estimated in males versus females [ES = 0.35 (95% HDI: 0.20 to 0.49); pd = 100%], however, relative increases in muscle size were similar between sexes [ES = 0.05 (95% HDI: –0.07 to 0.16); pd = 80%]. Sub-group analyses found that the balance of probability favoured relative type I muscle fibre hypertrophy in males versus females [ES = 0.57 (95% HDI: –0.02 to 1.16) pd = 97%] and relative type II muscle fibre hypertrophy in females versus males [ES = –0.36 (95% HDI: –0.97 to 0.23) pd = 89%]. Other variables assessed (i.e., body region, measurement, RT experience, set volume, relative load) did not have a meaningful impact on sex differences in relative muscle hypertrophy.
... In addition to their role in reproductive function, hormones can also influence the mechanical properties of reproductive tissues. For instance, there is evidence suggesting that female sex hormones may affect the structure and mechanical properties of the musculoskeletal system, potentially altering injury risk during certain phases of the menstrual cycle or during pregnancy 16 . From a tissue engineering perspective, it is essential to consider these dynamic mechanical properties while designing biomimetic reproductive tissues. ...
Understanding the mechanical properties and porosity of reproductive tissues is vital for regenerative medicine and tissue engineering. This study investigated the changes in Young's modulus (YM), storage modulus (E′), loss modulus (Eʺ), and porosity of native and decellularized bovine reproductive tissues during the estrous cycle. Testis tunica albuginea had significantly higher YM, E′, and Eʺ than the inner testis, indicating greater stiffness and viscoelasticity. Endometrium showed no distinct differences in YM, E′, or Eʺ across the estrous cycle or between horns. Ovaries exhibited significant variations in YM, E′, Eʺ, and porosity, with higher YM and E′ in the ipsilateral cortex and medulla during the luteal phase. Decellularized ovarian tissues displayed increased porosity. The oviduct displayed no significant differences in YM or E′ in the isthmus, but the contralateral ampulla had reduced YM and E′ in the luteal phase. These findings offer valuable insights into the dynamic mechanical properties and porosity of reproductive tissues, facilitating the development of biomimetic scaffolds for tissue engineering applications.
... First, we assessed the joint passive stiffness, while more information would come from an examination of the passive stiffness in each individual muscle. Second, we recruited a male sample, while it is known that women have a more compliant muscle-tendon unit than men [44] and different hormone levels that can change the outcomes of the stretching protocol on the connective muscle tissue [45]. Therefore, the present results cannot be extended to different populations. ...
This study investigated the synergistic difference in the effect of stretching on electromechanical delay (EMD) and its components, using a simultaneous recording of electromyographic, mechanomyographic, and force signals. Twenty-six healthy men underwent plantar flexors passive stretching. Before and after stretching, the electrochemical and mechanical components of the EMD and the relaxation EMD (R-EMD) were calculated in gastrocnemius medialis (GM), lateralis (GL) and soleus (SOL) during a supramaximal motor point stimulation. Additionally, joint passive stiffness was assessed. At baseline, the mechanical components of EMD and R-EMD were longer in GM and GL than SOL (Cohen’s d from 1.78 to 3.67). Stretching decreased joint passive stiffness [-22(8)%, d = -1.96] while overall lengthened the electrochemical and mechanical EMD. The mechanical R-EMD components were affected more in GM [21(2)%] and GL [22(2)%] than SOL [12(1)%], with d ranging from 0.63 to 1.81. Negative correlations between joint passive stiffness with EMD and R-EMD mechanical components were found before and after stretching in all muscles ( r from -0.477 to -0.926; P from 0.007 to <0.001). These results suggest that stretching plantar flexors affected GM and GL more than SOL. Future research should calculate EMD and R-EMD to further investigate the mechanical adaptations induced by passive stretching in synergistic muscles.
... Although previous measures of fatigue-induced reduction of whole-muscle stiffness included exclusively (Siracusa et al., 2019;Chalchat et al., 2020) or predominantly (Andonian et al., 2016) male participants, muscle stiffness appears to be influenced by biological sex, with women exhibiting reduced muscle stiffness compared to men (Kubo et al., 2003;Morse, 2011). These divergent mechanical properties have been attributed to the effects of sex hormones on whole-muscle (Chidi-Ogbolu & Baar, 2019;Ham et al., 2020) and tendon (Hansen & Kjaer, 2016) stiffness. In muscle, estrogen appears to support the maintenance of mass and strength, metabolic function, and connective tissue collagen turnover and incorporation (Chidi-Ogbolu & Baar, 2019). ...
... These divergent mechanical properties have been attributed to the effects of sex hormones on whole-muscle (Chidi-Ogbolu & Baar, 2019;Ham et al., 2020) and tendon (Hansen & Kjaer, 2016) stiffness. In muscle, estrogen appears to support the maintenance of mass and strength, metabolic function, and connective tissue collagen turnover and incorporation (Chidi-Ogbolu & Baar, 2019). Estrogen also renders ligaments and tendons more compliant in females compared to males (Hansen & Kjaer, 2016). ...
Previous studies demonstrated that acute, exercise-induced fatigue transiently reduces whole-muscle stiffness. Because reduced muscle stiffness at fatigue may contribute to increased injury risk and impaired contractile performance, the present study seeks to elucidate potential intracellular mechanisms underlying these reductions. To that end, cellular passive Young’s Modulus was measured in single, permeabilized muscle fibers from healthy, recreationally-active males and females. Eight volunteers (4 male, 4 female) completed unilateral, repeated maximal voluntary knee extensions until fatigue, after which percutaneous needle biopsies were performed on the fatigued (F) and non-fatigued (NF) Vastus Lateralis muscles. Muscle samples were processed for mechanical assessment and separately for imaging and phosphoproteomics. Single fibers were passively (pCa 8.0), incrementally stretched to 156% of the initial sarcomere length to assess Young’s Modulus, calculated as the slope of the resulting stress-strain curve at short (strain = 1.00-1.24 %Lo) and long (strain = 1.32-1.56 %Lo) fiber lengths. Titin phosphorylation was assessed by liquid chromatography followed by high-resolution mass spectrometry (LC-MS). Passive modulus was significantly reduced by fatigue at short and long lengths in male, but not female, participants. Fatigue increased phosphorylation of four serine residues located within the elastic region of titin and reduced phosphorylation at one serine residue but did not impact active tension nor sarcomere ultrastructure. Collectively, these results suggest muscle fatigue reduces cellular passive modulus in young males, but not females, concurrent with altered titin phosphorylation. These results provide mechanistic insight contributing to the understanding of sex-based differences in soft tissue injury and falls risk.
Key Points Summary
Previous studies have shown that skeletal muscle stiffness is reduced following a single bout of fatiguing exercise.
Lower muscle stiffness at fatigue may increase risk for soft-tissue injury, however, the underlying mechanisms of this change are unclear.
Our findings show that fatiguing exercise reduces passive Young’s modulus in skeletal muscle cells from males but not females, suggesting that intracellular proteins contribute to reduced muscle stiffness with fatigue in a sex-dependent manner.
The phosphorylation status of the intracellular protein titin is modified by fatiguing exercise in a way that may contribute to altered muscle stiffness after fatiguing exercise.
These results provide important mechanistic insight that may help explain why biological sex impacts risk for soft tissue injury in with repeated or high intensity mechanical loading in athletes and falls risk in older adults.
New and Noteworthy
Muscle fatigue has previously been shown to reduce musculotendinous stiffness, but the underlying mechanisms remain unclear. Our study presents novel evidence of fatigue-induced reductions in passive cellular Young’s Modulus in skeletal muscle from males, but not females, in conjunction with fatigue-induced alterations in titin phosphorylation. Collectively, these results suggest that intracellular mechanisms including titin phosphorylation may contribute to altered skeletal muscle stiffness following fatiguing exercise, and that this response is mediated by biological sex.
