The medication reportedly has no birth control effect.It has been suggested that the weak progestogenic activity of spironolactone is responsible for these effects, although this has not been established and spironolactone has been shown to possess insignificant progestogenic and antiprogestogenic activity even at high dosages in women. An alternative proposed cause is inhibition of 17α-hydroxylase and hence sex steroid metabolism by spironolactone and consequent changes in sex hormone levels. Indeed, CYP17A1 genotype is associated with polymenorrhea. Regardless of their mechanism, the menstrual disturbances associated with spironolactone can usually be controlled well by concomitant treatment with a birth control pill, due to the progestin component. Mood changes
Research is mixed on whether antimineralocorticoids like spironolactone have positive or negative effects on mood. In any case, it is possible that spironolactone might have the capacity to increase the risk of depressive symptoms. However, a 2017 hybrid systematic review found that the incidence of depression in women treated with spironolactone for acne was less than 1%. Likewise, a 10-year observational study found that the incidence of depression in 196 transgender women taking high-dose spironolactone in combination with an estrogen was less than 1%. Rare reactions
Aside from hyperkalemia, spironolactone may rarely cause adverse reactions such as anaphylaxis, kidney failure, hepatitis (two reported cases, neither serious), agranulocytosis, DRESS syndrome, Stevens–Johnson syndrome or toxic epidermal necrolysis. Five cases of breast cancer in patients who took spironolactone for prolonged periods of time have been reported. Spironolactone bodies
Long-term administration of spironolactone gives the histologic characteristic of "spironolactone bodies" in the adrenal cortex.
With RA, small joints are mostly affected in an inflammatory, destructive manner. This is not observed in IH. Rheumatoid factor, cyclic citrullinated peptide antibodies and antinuclear antibodies are usually negative in IH. Palindromic rheumatism. Like IH, palindromic rheumatism (PR) is also characterised by relapsing, short-episodes of sudden onset arthritis with no recognisable trigger. However, unlike PR, IH affects the knee almost exclusively and there is a predictable periodic, regularity of attacks, with laboratory tests during attacks being generally unremarkable. PR is also more likely to be associated with development of rheumatoid arthritis. Familial Mediterranean Fever. For some patients with FMF, episodes of knee or joint inflammation may be the only presenting symptom during an acute inflammatory episode. The MEFV gene mutations associated with FMF have been implicated in the pathogenesis of both palindromic rheumatism and IH. Other conditions for consideration (or exclusion) are other periodic arthropathies, crystal arthopathy, prepatellar bursitis (housemaids knee), pigmented villonodular synovitis, trauma and infectious causes. Treatment
No treatment has been found to be routinely effective. NSAIDs and COX-2 inhibitors are not generally helpful other than for general pain relief. They do not seem to help reduce effusions or prevent their occurrence. Low-dose colchicine (and some other ‘anti-rheumatic’ therapies e.g. hydroxychloroquine) have been used with some success. (Use of methotrexate and intramuscular gold have not been reported in the literature).