Why Knee Pain Increases in Women After Menopause — Dr. Moriwaki Organizes the Relationship Between Estrogen Decline and Knee Osteoarthritis, and the Option of Stem Cell Conditioned Media Injection into the Joint2026.07.19

“After entering my fifties, I began to feel discomfort in my knee and pain when going down stairs that I had never felt before.” Consultations like this from women are far from rare. It is known that the abrupt drop in estrogen that accompanies menopause exerts multifaceted effects on articular cartilage, the synovium, and bone metabolism, and raises the risk of onset and progression of knee osteoarthritis. In this column, Dr. Moriwaki of AVAN TOKYO Ginza sincerely organizes the medical background behind why knee pain increases in women after menopause, the position of conservative treatment, and how the option of stem cell conditioned media injection into the joint fits in. Because effects vary among individuals and appropriateness differs by disease stage, the first step is to obtain an accurate diagnosis.

Key Points of This Article

・Knee osteoarthritis surges in postmenopausal women, and estrogen decline pushes up onset risk through cartilage metabolism, synovial inflammation, and bone metabolism.

・Diagnosis is based on interview, physical examination, and weight-bearing plain X-rays, with MRI added when soft tissue evaluation is needed.

・The foundation of treatment is weight control, exercise therapy, and orthotic therapy — these must not be skipped.

・Stem cell conditioned media injection into the joint is one conservative option that aims to correct the inflammatory environment and prepare the tissue-repair environment; it is not a treatment that creates cartilage from zero.

・For end-stage joint destruction, total knee arthroplasty is the more realistic and reliable choice.

The Medical Background Behind the Sharp Rise in Knee Pain After Menopause

Between the late forties and the fifties, consultations for knee joint pain in women visibly increase. Epidemiological data indicate that women have roughly twice the prevalence of knee osteoarthritis compared with men of the same generation, and it is thought that the abrupt drop in estrogen during menopause is involved in that background.

The Protective Role Estrogen Played in Joint Tissue

Estrogen is not only involved in reproduction; it acts broadly on joint tissues as well. Chondrocytes express estrogen receptors and are involved in the maintenance of cartilage matrix synthesis and the suppression of inflammatory cytokines such as IL-1β and TNF-α. In the synovium, it works in the direction of restraining runaway inflammation, and in the subchondral bone it has the action of moderating bone resorption. When estrogen is rapidly lost through menopause, these protective actions all weaken at once, and a state emerges in which cartilage wear, chronic synovial inflammation, and abnormal remodeling of subchondral bone tend to advance simultaneously.

Subjective Symptoms That Appear in the Knee After Menopause

Specifically, stiffness of the knee at the first step in the morning, wobble and pain when going down stairs, difficulty standing up from a formal Japanese seiza position, and pain when pressing on the medial side of the knee all increase. These are typical symptoms of early- to mid-stage knee osteoarthritis, and if left untreated they progress to X-ray changes such as narrowing of the joint space and osteophyte formation. In addition, muscle mass tends to decrease after menopause, and atrophy of the quadriceps weakens shock absorption at the knee, creating a vicious cycle of pain and functional decline.

Diagnosis and Conservative Care as the Unshakable Foundation

Rather than deciding on your own that “it can’t be helped because it’s menopause,” it is important first to receive a diagnosis at an orthopedic clinic. Information on joint diseases from the Japanese Orthopaedic Association is also a useful reference.

The Roles of Interview, Examination, and Imaging

Diagnosis is based on the interview and physical findings — the location of pain (medial-type is most common), range of motion, swelling, and presence of joint effusion. A weight-bearing plain X-ray is used to assess narrowing of the joint space, osteophytes, and subchondral bone sclerosis, and the Kellgren-Lawrence classification grades the disease. MRI is added when differential diagnosis is needed for other pain sources such as meniscus tears, bone marrow edema, or pes anserinus bursitis.

The Pillars of Conservative Care — Exercise, Weight Control, and Orthotics

The first things to work on are weight control, strength training centered on the quadriceps, and stretching to preserve range of motion. It has been reported that a 1 kg reduction in body weight lightens the load on the knee during walking by 3–4 kg, so patient weight reduction connects directly to pain. Knee supporters, foot insoles, and, when needed, the use of a cane are effective means of buffering impact on the joint. Only when this foundation of conservative treatment is in place do injection therapies and regenerative-medicine approaches take on real meaning.

Stem Cell Conditioned Media Injection into the Joint as an Option for Knee Osteoarthritis

For patients with moderate knee osteoarthritis whose pain cannot be sufficiently controlled by conservative care and medication, or who feel they have hit a ceiling with hyaluronic acid injections, stem cell conditioned media injection into the joint is considered as one conservative option. For details, please also see our page on stem cell conditioned media joint injection.

How the Action Is Understood and the Range That Can Be Expected

Stem cell conditioned media contains growth factors such as TGF-β, IGF-1, FGF, and VEGF, as well as anti-inflammatory cytokines and exosomes. Injecting it into the joint space is thought to work in the direction of correcting chronic synovial inflammation and preparing the repair environment of cartilage, subchondral bone, and ligaments. However, it is not “an injection that regenerates cartilage from zero”; rather, it acts on the intra-articular inflammation and repair environment to aim at improvement of pain and function. Effects vary among individuals, and the expected value declines as the KL grade advances. For cases in which end-stage joint destruction has progressed, total knee arthroplasty is the more realistic and reliable option.

Distinguishing It from Hyaluronic Acid and Steroid Injections

Hyaluronic acid injection is a physical approach that supplements joint-fluid lubrication and viscoelasticity, and steroid injection is a pharmacological approach that suppresses acute-phase pain with strong anti-inflammatory action. Stem cell conditioned media joint injection has a different axis of action from these; it is a biological approach aimed at correcting the inflammatory environment and preparing the tissue-repair environment. There is no need to see the three as mutually exclusive — a realistic way of thinking is to use them differently, or combine them, according to disease state and timing.

Frequently Asked Questions

Q. Can menopausal knee pain be prevented with hormone replacement therapy (HRT)?

There are observational studies suggesting HRT may suppress progression of knee OA, but clear evidence for preventive use has not been established. When HRT is indicated as treatment for menopausal symptoms, a secondary positive effect on the knee may be expected, but starting HRT solely to prevent knee pain is not recommended. Please consult with both gynecology and orthopedics and judge comprehensively.

Q. How many times should stem cell conditioned media knee-joint injections be received?

A common protocol is multiple sessions at 2–3 week intervals in the induction phase, then switching to maintenance-phase intervals depending on progress and symptoms. The number and interval should be individually designed based on disease state and response, so please decide in consultation with your treating physician.

Q. I have already been recommended joint replacement surgery. Can conditioned media injection help me avoid it?

When end-stage joint destruction is causing major impact on daily life, total knee arthroplasty is the option that will more reliably restore quality of life. Choosing conditioned media injection with the sole aim of avoiding surgery is not recommended. Please consider it at the moderate stage or earlier, as an option combined with conservative treatment.

Q. If I lose weight, will injections become unnecessary?

Weight management is one of the most powerful conservative measures, but once changes have already occurred in cartilage or synovium, weight loss alone may not fully relieve pain. A realistic approach is to build on a foundation of weight loss and exercise therapy and add injection treatment as needed.

Q. Is there a risk of intra-articular infection?

Even with strict aseptic technique, intra-articular infection is not zero-risk. In backgrounds such as poorly controlled diabetes, active infection, or ongoing use of immunosuppressants, careful judgment is required. Please share any concerns in advance without hesitation.

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【Medical Supervisor】Shin Moriwaki (Supervising Physician)

Member, Japan Society of Aesthetic Surgery (JSAS) / Member, American Academy of Aesthetic Medicine

ECFMG Certificate (U.S. Medical Licensing Qualification)

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📍AVAN TOKYO Ginza Regenerative Medicine

AVAN TOKYO Ginza Regenerative Medicine

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