Second Chapter
Dr. Álvaro Monterrosa Castro, MD
Hyperkeratinization of the follicular epithelium
Acne is characterized by hyperkeratinization of the follicular epithelium with secondary effects on the sebaceous glands. The anaerobic bacterium Propionebacterium acnes is involved in the conversion of non-inflammatory to inflammatory lesions (120). One in two women is considered to have excessive facial fat production after puberty.
In the United Kingdom, the presence of facial acne has been documented in 54% of women over 25 years of age. Likewise, in a French study it has been observed that in women between 25 and 40 years of age the presence of acne is 41% (120). In turn, the existence of seborrhea can be a precondition for acne.
The skin, hair follicles and sebaceous glands are the target organs of sex hormones, and androgens stimulate oil production by the sebaceous glands. Just as they stimulate the hair follicles, therefore the androgenic or antiandrogenic potency of the progestin may be the generating center of the differences.
If the progestin has an androgenic effect, there is usually aggravation of acne, but if the substance is antiandrogenic, there may be a notable improvement in the health of the skin (56).
The action of combined oral contraceptives in androgenic skin disorders depends largely on the balance of estrogen and progestin.
Acne worsens if there is a marked estrogenic effect, due to the predominance of a progestin with poor antiestrogenic effect or high androgenic properties (120).
Gestodene, Desogestrel and Norgestimate
Combined oral contraceptives containing Gestodene, Desogestrel and especially Norgestimate. They increase the concentration of Sex Hormone Binding Globulin (SHBG) in the serum. Therefore, they reduce free testosterone (54), producing an antiandrogenic effect, which clinically translates into an improvement in acne (50).
Another mechanism by which these oral contraceptives provide improvement in acne is due to the antiestrogenic effect of the aforementioned progestins. Drospirenone, chlormadinone, dienogest and cyproterone have antiandrogenic activity (56). In turn, norgestimate does not have androgenic properties (58).
Androgenic disorders in women’s skin lead to hirsutism, acne and alopecia, all of which are fundamentally caused by excess androgens. The activity of dermal 5 alpha reductase is the factor that most influences the manifestations of androgenic excess in women.
Treatment of androgenic skin disorders
Combined oral contraceptives are helpful in the treatment of androgenic skin disorders. Since they can decrease androgen levels by inhibiting 5 alphareductase and can inhibit activity at the androgen receptor (121).
Rabe and collaborators (121), studying progestins in vitro, found the following order in the ability to block 5 alpha reductase in skin: norgestimate, dienogest, cyproterone and Gestodene. They consider (121) that these progestins, mainly norgestimate, are of great help in the treatment of hyperandrogenism in women.
The antiandrogenic action of Dienogest, a progestin that induces a decrease in the concentration of free testosterone and androstenedione, is well known. With a favorable effect on the hair follicle and sebaceous glands (56). Desogestrel 150 ug/day plus 30 ug/day of ethinyl estradiol is also effective in these aspects, in the opinion of Comporato et al (122).
Oral contraceptives are frequently used in the treatment of acne to modify the excessively androgenic hormonal environment and reduce lesions. Even very low-dose combined oral contraceptives are still beneficial for women who have androgenic conditions such as acne (84,123).
Desogestrel, developed in the mid-1970s, is part of the gonans and is derived from 19-nortestosterone. Escobar-Morreale et al (124) assert that microdose oral contraceptives that include 30 ug/day of ethinyl estradiol and 150 ug/day of desogestrel. They are effective in controlling hyperandrogenism, hirsutism and improve abnormal metabolic profile as well as insulin level and insulin resistance.
Thorneycroft et al (50) have the same opinion and assert that levonorgestrel reduces androgenic levels in the adrenals, ovaries and peripheral tissues. While norethindrone reduces only the adrenals.
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Very low dose combined oral contraceptives
Very low-dose combined oral contraceptives containing 20 ug/day ethinyl estradiol plus 100 ug/day levonorgestrel are very effective in reducing circulating androgens and acne. Without causing weight gain (50).
Drospirenone has a significantly beneficial effect against acne plus the antiandrogenic effect by blocking androgen receptors. This reduces excess sebum secretion. Bacterial colonization of the ducts is reduced and inflammation is reduced.
Mármol et al (120) refer to the multicenter, randomized clinical trial. Compared with placebo, Katz’s double-blind study evaluated the efficacy of a triphasic combined oral contraceptive that includes ethinyl estradiol plus desogestrel (Laurina) in 41 women, with follow-up for six cycles. Where it is observed that the relative reduction in sebaceous fat production by the pill is 61% in the cheeks, 30% in the forehead and 15% in the chin with the use of the pill.
Likewise, in another study it had been observed that the combination ethinyl estradiol plus desogestrel offered a significant decrease in the production of facial seborrhea after one to three cycles of treatment. When compared with placebo (120).
The combination of 30 ug/day of ethinyl estradiol plus 3 mg/day of the new progestin drospirenone has recently been introduced and two clinical trials have already been published.
A comparative study has been carried out to measure the impact on acne and seborrhea, using 30 ug/day of ethinyl estradiol plus 3 mg/day of drospirenone versus 35 ug/day of ethinyl estradiol plus 2 mg/day of cyproterone acetate.
After nine cycles of use, both combinations effectively reduced facial lesions, inflammation, sebum production and hair growth.
The marked reduction in fat production could be determined from the initial treatment cycle. At the end of the nine months the reduction in mean production with the pill that included drospirenone was 25.1% compared to 39.3% with the pill that included cyproterone.
The drospirenone pill induced a 56% reduction in testosterone concentration while the reduction induced by cyproterone was 66%. Both combinations also favorably reduce Dehydroepiandrostenedione sulfate and androstenedione sulfate.
The antiandrogenic potency of drospirenone is generally considered to be approximately one-third that of cyproterone (56).
In the other trial, a reduction in the incidence of seborrhea between 3% and 12% was observed after thirteen cycles of use of a pill containing drospirenone. Similar results to those obtained with pills containing desogestrel (120).
Chlormadinone acetate, a new antiandrogenic progestin derived from hydroxyprogesterone, has also recently been used. Which is available in a combined contraceptive preparation at a rate of 2 mg/day plus 30 ug/day of ethinyl estradiol.
In an open phase III study, improvement in seborrhea was observed in 68% of women who used this pill for twelve treatment cycles. 58% of the women who participated were completely cured of seborrhea.
In the German multicenter study, a significant benefit of ethinyl estradiol plus chlormadinone versus ethinyl estradiol plus levonorgestrel was observed in women with mild or moderate acne.
59% of women who received the first pill responded with more than 50% improvement in papules and pustules after twelve treatment cycles compared to 46% who received the second pill.
Acne deterioration was observed in 11% of women using the levonorgestrel pill and in none of those taking the chlormadinone pill.
In another study, comparing the drospirenone pill with a 30 ug/day ethinyl estradiol pill plus 150 mg/day levonorgestrel. Resolution of seborrhea was observed in 80% of the women who received the first and in 76% of those who received the second, after twelve cycles of treatment (120).
For its part, cyproterone acetate is an antiandrogenic progestin that blocks the androgen receptor. It has a powerful progestational action and is available within the contraceptive pill at a rate of 2 mg/tablet plus 35 ug/tablet of ethinyl estradiol.
This pill is indicated only for women who require antiandrogen therapy due to acne, alopecia and hirsutism. Its effectiveness being very well documented. Demonstrating marked improvement in the count of injuries and their severity.
Therapy with oral contraceptives is one of the therapeutic options to be applied to women with acne.
The pill of 35 ug/day of ethinyl estradiol plus 2 mg/day of cyproterone is considered the “gold standard” for the use of oral contraceptives in acne and is the only combination that has shown evident efficacy in severe acne. Condition in which desogestrel, drospirenone and chlormadinone also have a cavity.
All modern oral contraceptives that include new generations of progestins are generally beneficial for moderate acne and seborrhea (120).