Hormonal Influences on Pain Perception across the Menstrual Cycle

The female menstrual cycle comprises dynamic fluctuations in oestrogen and progesterone that profoundly influence both peripheral and central mechanisms of pain modulation. During the follicular phase, rising oestrogen levels enhance endogenous opioid activity and raise pain thresholds, whereas the mid-luteal surge in progesterone may attenuate certain nociceptive pathways but also interact with inflammatory mediators to heighten sensitivity. These hormonal shifts alter ion channel expression, synaptic neurotransmission and descending inhibitory control, giving rise to phase-dependent variability in pressure, ischaemic and thermal pain responses. Clinically, such variation underpins cyclical patterns of migraine, dysmenorrhoea and musculoskeletal discomfort, and informs the timing of analgesic interventions and experimental pain protocols. Understanding the interplay between sex steroids and nociceptive circuits is therefore essential for optimising pain management in women and for designing inclusive clinical trials that account for menstrual-phase effects.

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Hormonal Influences on Pain Perception across the Menstrual Cycle publication trend

The graph below shows the total number of articles in hormonal influences on pain perception across the menstrual cycle across all publications each year (not limited to Nature Index journals).

Technical terms

Nociception: The neural processes of encoding and processing noxious stimuli.

Sensory threshold: The minimal stimulus intensity perceived as painful.

Follicular phase: The menstrual phase from cycle onset to ovulation, characterised by rising oestrogen.

Luteal phase: The post-ovulation phase marked by elevated progesterone and moderate oestrogen.

Δ-Opioid receptor: A subtype of opioid receptor involved in modulating spinal pain transmission.

Ischaemic pain threshold: The pressure or stimulus level at which ischaemia-induced discomfort is first reported.

Progesterone: A steroid hormone secreted by the corpus luteum that influences reproductive tissues and neural circuits.

References

1. Modulação pela progesterona da sensibilidade dolorosa a estímulos mecânicos e isquêmicos em mulheres saudáveis e jovens. Revista Brasileira de Ginecologia e Obstetrícia (2008).
2. The effect of progesteron for expression delta (δ) opioid receptor spinal cord through peripheral nerve injury. Annals of Medicine and Surgery (2022).
3. The Effects of Sex, Women’s Body Composition and Monthly Cycle Phases on the Sensory Threshold of Upper Limb to Transcutaneous Electrical Nerve Stimulation in Healthy Subjects. Applied Sciences (2023).