Table 3.
Study ID | Prospective? | What was reported | Age range, years | Primary diagnosis | Secondary diagnoses | Diagnoses excluded | Dose of spironolactone | Duration of therapy, months | Concomitant medications |
---|---|---|---|---|---|---|---|---|---|
Azizlerli et al. [40] | Yes (clarified by email) | Efficacy and safety | 18–33 | Acne | Hirsutism 9, menstrual irregularities 7 | NR | Starting at 200 mg and reducing to 100 or 50 mg/day over 5 months | 1–18 (mean 9) | Levonorgestrel/EE 12 |
Beksac et al. [41] | Unclear | Efficacy and safety | 18–27 | Idiopathic hirsutism | Therapy resistant acne 7, menstrual irregularities 6 | Obesity, major abnormalities in serum androgens | 50 mg bid (n = 16); 50 mg/day (n = 6) from days 5 to 26 of the menstrual cycle | 9 | NR |
Bravo Garcia et al. [42] | Unclear | Efficacy and safety | 12–37 | Acne | Polycystic ovaries 35, idiopathic hyperandrogenemia 18, hirsutism and/or irregular menses 23 | Hyperthyroidism, hyperprolactinemia, congenital adrenal hyperplasia, Cushing’s syndrome, ovarian and adrenal tumors |
50 mg bid from days 5 to 21 of the menstrual cycle | 6 | None permitted |
Burke and Cunliffe [43] | Unclear (probably retrospective) | Efficacy | NR | Acne 8, hirsutism 12, alopecia 7 | Primary diagnoses were mutually exclusive | NR | 200 mg/day | 6 | NR |
Cortez de Castro et al. [44] | Unclear | Efficacy and safety | 18–44 | Persistent recalcitrant acne | None reported Patients were otherwise healthy | No evidence of endocrinopathies, no menstrual irregularities | 2 × 25 mg bid (12 h apart) from start of menstruation for 15 days | 1–11 | NR |
Hana et al. [45] | Unclear | Efficacy and safety | 24–34 | Hirsutism | Seborrhea 6, Abnormal menses 5, PCOS 4, adrenal carcinoma 1, acromegaly 1 |
NR | 75 mg/day | 24–34 | NR |
Hughes and Cunliffe [46] | No | Efficacy (not properly reported) and safety | 21–51 | Hirsutism 24, acne 21, acne and hirsutism 8, seborrhea 1 | NR | NR | 200 mg/day initially, reduced in 8 patients as not tolerated | 1–45 | Unspecified oral contraceptive in 23 patients |
Krunic et al. [47] | Yes | Efficacy and safety (latter not properly reported) | 18–43 | Severe papulo-pustular or nodulo-cystic acne that had failed to respond to at least one standard treatment | None reported | Pre-existing hyperkalemia, liver or kidney disease, diabetes mellitus | 100 mg od in the morning | Up to 6 | Drospirenone/EE. Previously prescribed topical acne treatments continued |
Lessner et al. [48] | No | Efficacy and safety | 19–57 | Cyclical late-onset acne vulgaris (i.e. acne worsening premenstrually, with lesions predominantly on the lower face and neck) |
NR | Receiving oral or topical antibiotics or treated with PDT | Initial dose 50 mg/day, escalated to 200 mg/day as and when necessary in 25 mg increments every 3 months. 11 patients were increased to 75 mg, and 4 were increased from 75 to 100 mg | 2–102 | Majority also treated with topical tretinoin Or Adapalene™ at bedtime. Most had been receiving the topical retinoid prior to starting spironolactone |
Lubbos et al. [49] | Unclear | Efficacy and safety | 14–38 | Idiopathic acne | Oligomenorrhea 13 | NR | 50 mg bid on days 5–21 of the menstrual cycle | 2–49 Therapy continued unless ‘significant’ adverse effects occurred |
NR |
Masahashi et al. [50] | Unclear | Efficacy and safety | 21–36 | Hyperandrogenism | Oligomenorrhea 8, amenorrhea 9, acne and oily skin 5, oily skin 1, hirsutism 1, hirsutism 9, oily skin 1 | NR | 100–150 mg/day from day 5 of the menstrual cycle, then continuously | 2–11 (mean 4.4) | None 7, clomiphene (100 mg/day for 5 days from week 4) 10, plus bromocriptine (1.5–2.5 mg/day from week 8) in 3 patients |
Messina et al. [51] | No | Efficacy (not properly reported) and safety | 19–33 | Hirsutism without any other sign of virilization | Acne (unknown number), seborrhea (unknown number), PCOS 1 All but the PCOS case had regular menses |
Hirsutism associated with congenital adrenal hyperplasia or androgen-secreting tumor | Group A (n = 10): 400 mg/day for first 10 days then 200–300 mg. Group B (n = 8): 200 mg/day continuously Therapy started on the fifth day of the menstrual cycle in both groups |
Up to 8.3 | NR |
Pugeat et al. [52] | Unclear | Efficacy and safety | 16–42 | Hirsutism | Amenorrhea 8 | ‘Associated pathologies’ | 75 mg/day from the start of menstruation Demegestone 0.5 mg on days 14–24 of the cycle added from month 7 | 12 | None permitted |
Plovanich et al. [53] | No | Safety (serum electrolyte data only) | 18–45 | Acne | Endocrine disorders including PCOS, hirsutism, alopecia, and hyperandrogenism 298 | Heart failure, renal failure, renal disease | 50–200 mg/day (personal communication) | NR | NR |
Saint-Jean et al. [54] | Unclear | Efficacy and safety | >20 | Recalcitrant acne | One patient had PCOS, 5 had irregular menses, 4 reported a premenstrual flare | NR | 75–150 mg/day | Mean 17 months | A topical acne treatment (not specified) |
Sato et al. [55] | Yes | Efficacy and safety | 15–46, both genders | Acne | NR | NR | 200 mg/day for first 8 weeks, then reduced by 50 mg every 4 weeks | 5 months | NR |
Shaw [56] | No | Safety (serum electrolyte data only) | NR | Acne | NR | NR | 50–150 mg/day | NR | NR |
Shaw [57] | No | Efficacy and safety | 18 –52 | Inflammatory papular or nodular acne in 51/85 cases of adult onset; recalcitrant in 76 cases | Hormonal influence 68, hirsutism 16, menstrual flare 23, history of ovarian cysts 4 | NR | 50–100 mg/day | 2–24 (mean 10) | Oral antibiotics, COC (norethindrone/EE), or both. 17 patients (20%) were treated with spironolactone alone; 46 (54%) were treated with a combination of spironolactone and systemic antibiotics; 10 (12%) received spironolactone plus oral contraceptives; 12 (14%) received spironolactone plus antibiotics and oral contraceptives |
Shaw and White [58] | No | Safety | 18–52 | Adult acne | NR | NR | 50–100 mg/day | 0.5–122 (mean 28.5) | Topical therapies, systemic antibiotics or oral contraceptives |
Turowksi and James [59] | No | Efficacy and safety | 18–59 | Recalcitrant acne | NR | NR | 50–100 mg, decreasing according to response. One patient receiving 200 mg/day | Mean 19.5 | Trimethoprim 2, cotrimoxazole 3 or amoxicillin 2 initiated at the same time as spironolactone. Concomitant topical medications (started earlier) included topical retinoid 22, azelaic acid 4 and benzoyl peroxide 11. 14 or 15 women were already taking a COC, 2 were using a depot hormonal contraceptive, and 4 were started on a COC |
Yemisci et al. [60] | Yes | Efficacy and safety | 18–31 | Acne in adult females | NR | Pregnant women, women using oral contraceptives or other drugs with possible effects on hormone levels, and women with irregular menstruation or hirsutism were excluded | 50 mg bid on days 5–21 of the cycle | 3 | Not permitted |
od once daily, bid twice daily, COC combined oral contraceptive, EE ethinyl estradiol, PCOS polycystic ovarian syndrome, PDT photodynamic therapy, NR not reported