Patient case (clinical description): A 66-year-old woman comes to the office due to joint pain in the hands and periodic morning stiffness that lasts less than 15 minutes.  The pain is moderately severe and worsens with daily activity. The patient used Tylenol with minimal relief.  Past medical history is notable for hypertension and hypercholesteremia.  Physical examination shows firm nodules over the distal interphalangeal joints, bilaterally. The patient has pain in her knees as well. The knees are stiff in the morning for less than 30 minutes and become worse with climbing stairs. She has some sensation of bone friction during activity. X-ray shows narrowing of the joint space, subchondral bone sclerosis and osteophyte formation along the joints.

Patient's own account: I'm a 66-year-old woman and I went to my doctor's office because of a bloody joint pain in my hands that has been lasting for a while. The pain comes and go in the morning usually. I feel like a stiffness that last less than 15 minutes. The pain is moderately severe but it gets worse when I'm using my hands. I used Tylenol which helped a little. Apart from that, I suffer from hypertension and high cholesterol. The doctor made me notice that I have bumps around both of my hand joints. I also suffer from my knees and they are also stiff in the morning for around 30 min. It's even worse when I climb up the stairs! I also feel like my bones are rubbing against each other when I'm moving. The X-ray showed that I have narrow joint space, I have sclerosis, and abnormal growths of bone along my joints.

Clinical trial: Can we Use Estrogen-containing Therapy to Improve Pain in Women After Menopause With Hand Osteoarthritis?

Eligibility criteria:
Inclusion Criteria:

          -  Able to give informed written consent

          -  Female, aged 40-65 years old

          -  In those with an intact uterus: At least 12 months of spontaneous amenorrhea (without
             any menstrual bleeding in last 12 months) and last menstrual period not more than 10
             years ago

          -  In those who have undergone hysterectomy or are/were using an intrauterine
             contraceptive device with progesterone local therapy (such as Mirena): Follicle
             stimulating hormone (FSH) ≥30 milli-International Units per millilitre (mIU/ml) on
             screening blood test AND a history of menopausal symptoms in the last 1 to 10 years,
             in keeping with appropriate timing of menopausal status

          -  Hand pain, aching or stiffness on most days in the last 3 months

          -  At least 2, painful hand joints of any type (interphalangeal joints (IPJ) or base of
             thumbs)

          -  Fulfils American College of Rheumatology clinical diagnostic criteria for hand OA (3
             or more of following):

               1. Hard tissue enlargement of 2 or more of the following joints: 2nd or 3rd distal
                  interphalangeal joints (DIPJ), 2nd or 3rd proximal interphalangeal joints (PIPJ),
                  first carpometacarpal joints (CMCJ)

               2. Hard tissue enlargement of 2 or more of the DIPJs

               3. Less than 3 swollen metacarpophalangeal joints (MCPJ)

               4. Deformity of at least one of the joints listed in first point

        OR, for those with base of thumb osteoarthritis only not fulfilling these criteria, has
        clinical symptoms and examination findings consistent with base of thumb osteoarthritis.

          -  Hand pain has not responded adequately to National Institute for Health and Care
             Excellence core guidance for management of OA, including the use of paracetamol or
             non-steroidal anti-inflammatory drug (NSAID) gel, except where there is
             contraindication or intolerance

          -  Average hand pain is reported as typically more than 4 out of 10 in severity, or
             average hand pain in the last 7 days of 4/10 or more on a visual analogue scale

          -  In the Investigator's opinion, is able and willing to comply with all study
             requirements

        Exclusion criteria

          -  Other cause of hand pain, including inflammatory arthritis, connective tissue
             disorder, chronic pain or alternative clinical diagnosis such as tenosynovitis or
             carpal tunnel syndrome

          -  Pregnancy or breast feeding, or risk of this during study

          -  Use of one or more prohibited treatments within specified timeframe, or not willing to
             avoid treatment for the duration of the study:

               -  Oral contraceptive pill, or systemic HRT within the last 6 months (Use of an
                  intrauterine contraceptive device with progesterone local therapy (Mirena) or
                  vaginal topical estrogen use (known low systemic absorption) are not exclusions
                  to participation)

               -  Anti-estrogen medication within the last 6 months

               -  Oral, intramuscular or intraarticular steroid within the last 3 months

               -  Intraarticular hyaluronan to a hand joint within the last 6 months

               -  Initiation of new oral analgesia within the last 4 weeks

               -  Initiation of glucosamine, chondroitin, hand exercises or other relevant non-
                  pharmacological therapy within the last 6 weeks

               -  Hand surgery within the last 6 months, or planned within the next 6 months

               -  Medications likely to increase hepatic metabolism of study medication, including:

               -  St. John's Wort

               -  Anti-convulsants (phenobarbital, phenytoin, carbamazepine, lamotrigine)

               -  Some anti-infectives (rifampicin, rifabutin, nevirapine, efavirenz, ritonavir and
                  nelfinavir)

          -  Presence of one or more medical contraindications to the use of systemic hormonal
             replacement therapy:

               -  In those aged 40-45 years, FSH <30 mIU/ml on screening blood test, i.e. non-
                  confirmatory of menopausal status

               -  Any history of breast, endometrial, ovarian or skin cancer

               -  Any other history of other cancer within 5 years (except treated Basal Cell
                  Carcinoma, BCC)

               -  Relevant breast issue on routine national breast screening in prior 3 years

               -  Undiagnosed genital bleeding, or untreated endometrial hyperplasia, active
                  uterine fibroids or endometriosis

               -  Active or past history of venous thromboembolism (VTE) (including deep venous
                  thrombosis, pulmonary embolism and retinal vein thrombosis), or at high risk of
                  VTE (such as known thrombophilic disorders (such as Protein C, S or anti-thrombin
                  deficiency) or presence of a strong family history of VTE). Women with a first
                  degree relative with a history of VTE, or other strong family history of VTE at
                  the Investigators' discretion.

               -  Active or past history of arterial thrombo-embolic disease (such as myocardial
                  infarction, angina or stroke) or strong family history of stroke)

               -  Clinically significant immobility

               -  Migraine or active epilepsy

               -  Uncontrolled hypertension (or diastolic pressure greater than 90 mmHg or systolic
                  pressure greater than 145 mmHg at screening visit)

               -  Uncontrolled diabetes mellitus or uncontrolled hypertriglyceridaemia

               -  Body Mass Index (BMI) greater than 30

               -  Active malabsorption syndrome or clinically significant small bowel disease

               -  Acute liver disease, clinically significant abnormal liver function, active
                  gallbladder disease or porphyria

               -  Clinically significant renal impairment

               -  Intolerance to lactose, fructose or glucose (including galactose intolerance,
                  lactase deficiency, fructose intolerance, glucose-galactose malabsorption or
                  sucrase- isomaltase insufficiency)

               -  Known sensitivity to either conjugated equine estrogens, bazedoxifene or the
                  combination

          -  Any other significant or uncontrolled disease or disorder which, in the opinion of the
             Investigator, may either put the participants at risk because of participation in the
             study, or may influence the result of the study, or the participant's ability to
             participate in the study

          -  Participants who have participated in another research trial involving an
             investigational product in the past 8 weeks
Female
No healthy subjects accepted to join the trial.
Subject must be at least 40 Years old.
Subject must be at most 65 Years

Eligibility (NLI label): Contradiction