Management of women with hirsutism in Kosovo

Introduction

Hirsutism is excessive body hair on parts of the woman’s body where hair is normally absent or minimal. Hirsutism can be a sign of other conditions: the polycystic ovary syndrome (PCOS), androgen-secreting tumours, non-classic adrenal hyperplasia (NCAH), or syndromes of severe insulin resistance, rather than an isolated disorder. “Idiopathic hirsutism” (IH) is an exception, because its etiology is unknown [1]. While it is not a life-threatening condition, hirsutism can lead to feelings of self-consciousness and social anxiety. The treatment of women with hirsutism can be done with methods that target the manifestations of hirsutism and pharmacological therapy that treats the causes or diseases that cause hirsutism [2]. When treating clinical manifestations, physical methods of hair removal are used, from the use of razor blades to laser therapy, topical treatment and weight loss [3]. It is important that overweight and obese women are encouraged to lose weight, because in this way the level of sex hormone binding globulin (SHBG) increases and the level of androgens in the serum decreases as well as the level of luteinizing hormone (LH) decreases, but also insulin resistance [4].

Women who have hyperandrogenemia, hyperinsulinism and overweight should be consulted because there is a risk of developing diabetes mellitus and cardiovascular diseases [5].

The use of medicines is important because they treat the cause of hirsutism, while cosmetic treatment is done to make the patient satisfied. Antiandrogens are used to block androgens at multiple levels. Therefore, they are used as combination oral contraceptives (OCP), 5a-reductase inhibitors (finasteride), nonsteroidal antiandrogens (flutamide) and steroid androgens (spironolactone). An antiandrogen and progestin medication (cyproterone acetate) are no longer used. In the etiology of hirsutism with PCOS, insulin sensitisers should be used [6–8].

Combined oral contraceptives containing ethinyl estradiol and a pregestational agent are used for the management of hirsutism (especially facial hirsutism) because they have an antiandrogenic effect [8].

They suppress the secretion of LH and reduce the secretion of androgens because they increase the level of SHBG. Most often they contain 30 µg of ethinyl estradiol, with 2 mg of cyproterone acetate (CPA) or 3 mg of drospirenone (DRSP). A reduction in the rate of hirsutism has also been observed with the use of OCPs containing CPA and DRSP [9].

CPA is a derivative of 17-hydroxyprogesterone acetate that competes with dihydrotestosterone (DHT) to bind to androgen receptors and thus lowers the level of LH, which lowers the level of testosterone and androstenedione. The effect of oral contraceptives is more pronounced after 6 cycles and continues to be even further but to a lower degree [10].

Co-cyprindiol (Dianette) is a combined hormonal preparation containing cyproterone-acetate (2 mg) and is licensed for the treatment of severe acne and higher-grade hirsutism. It is thought that long-term use may increase the risk of thromboembolism, more often with the use of co-cyprindiol than with other oral contraceptives, but in practice they are very well tolerated [11, 12].

Flutamide is a nonsteroidal inhibitor of androgen receptors. It is hepatotoxic. It is used only in women in whom estrogen therapy is contraindicated. It can cause feminization of the male foetus; therefore, women of reproductive age who are treated with flutamide must use effective contraception [13].

5α-reductase inhibitor is a competitive inhibitor of 5α-reductase; therefore, it is effective in the treatment of hirsutism causing relatively few side effects. Response to antiandrogens is slow and may take up to 18 months. The duration of therapy is unclear, but discontinuation of therapy causes regrowth of hair [14].

5α-reductase inhibitor works by this mechanism: 5α-reductase type I and type II are responsible for 1/3 to 2/3 of DHT production in the body. It prevents the conversion of testosterone to DHT by the type II isoenzyme resulting in a 65–70% reduction in DHT levels. Despite blocking both 5α-reductase enzymes that can reduce whole-body DHT levels by more than 99%, 5α-reductase inhibitor cannot completely suppress DHT production because it has significantly less effect on type I 5α-reductase compared to type II [15].

5α-reductase inhibitor causes the following side effects: gastrointestinal disorders, decreased libido, hepatotoxicity and feminization of the male foetus, therefore contraceptive measures should be taken in women of reproductive age [16].

Accompanying diseases should be identified such as: endometrial hyperplasia or carcinoma, dysfunctional uterine bleeding, type 2 diabetes mellitus, and dyslipidemia. They could be treated with insulin sensitisers, lipid-lowering agents and lifestyle modification.

Metformin is an antidiabetic drug of the biguanide class. It is the drug of first choice in diabetes, overweight and obesity, in people with normal kidney function. Metformin is less effective in reducing hirsutism. Metformin is very effective in inducing ovulation in women with PCOS [17].

Mechanical hair removal methods are used in mild forms of hirsutism, such as hair removal by the patients themselves, using a razor, bleaching with hydrogen peroxide, depilatory cream, and electrolysis, and can be completely sufficient [18].

Root hair extraction with tweezers is mainly practiced in regions that have few hairs such as the face region, but it is painful and takes time. Shaving with a guard razor is used for legs and underarms. It is thought that razor shaving causes the rapid growth of thicker hairs, but it is known that razor shaving does not increase either the diameter or the rate of hair growth, but can cause irritation, folliculitis, pseudofolliculitis and infection [19].

Wax is used to remove the hair by the root, it is a little more expensive than using tweezers, but the serial hair removal is slow and takes several weeks. It can cause pain, burning, irritation, folliculitis, scars, and post-inflammatory dyspigmentation. Different bleaching products are not effective especially on dark hairs and can cause skin irritation [20].

Similar results are obtained with the use of chemical depilatories such as the use of razors, but skin irritation appears more often. Acid preparations of thioglycol are used for this purpose. They are cheap, they do not cause pain but the effect is short and irritant dermatitis may appear [21].

The most effective and permanent method is electrolysis, where the follicle is treated individually with electric current. It can be combined with drug therapy as well as with the use of the laser [21, 22].

There are a variety number of lasers and Intense Pulsed Light (IPL) systems that are effective for long-term hair reduction. They act on the hair shaft, follicular epithelium and hair matrix, emitting light with wavelengths ranging from 600 to 1200 nanometres (nm), which is selectively absorbed by melanin [22, 23].

Material and methods

It is a prospective study, which included 135 women with hirsutism, who were of reproductive age. The research started on 16.09.2011 and was completed on 20.10.2012. Women were checked for hair growth in androgen-sensitive areas, disorders in the menstrual cycle or infertility. Premenarchal, postmenopausal women, those with corticosteroid therapy and oral contraceptives, pregnant women, as well as women who for other reasons did not come to give blood on time, even after the evaluation and detailed collection of data, were excluded from the research.

The questionnaire was completed with detailed data for each patient, history of hirsutism and other diseases, the degree of menstrual disorder, emotional state and psychological changes, the presence of galactorrhea, infertility, acanthosis nigricans, the degree of development of the breasts was also assessed. Body weight and height were measured and BMI was calculated.

The evaluation of hirsutism was done with the Ferriman-Gallwey scale in 11 androgen-sensitive areas, where the scale above 8 is considered hirsutism. Acne was evaluated using standard methods.

To investigate all hormones, blood was taken in the early follicular phase (day 3–5) of the menstrual cycle, for progesterone in the luteal phase (day 21), and for amenorrhoeic women, on an arbitrary day. The blood sample was taken early, at 8 o’clock in the morning, and for cortisol in the evening, at 6 o’clock. The serum was separated by centrifugation and stored in a refrigerator at –20°C. The level of hormones was determined by the RIA method (estradiol, progesterone, 17-OH progesterone, testosterone, free-testosterone, androstenedione, DHEASO4, cortisol, T3, T4, TSH) and with the IRMA method (FSH, LH, prolactin, SHBG, ACTH) using commercial kits from the manufacturer, Immunotech, USA.

Data processing was done with the statistical package InStat 3.

Results

According to the etiology, 43 or 31.9% of women with hirsutism had hyperandrogenemia, 37 or 27.4% had PCOS, 29 or 21.5% had idiopathic hirsutism, while 26 or 19.3% had non-classic congenital adrenal hyperplasia (NC CAH). 5.2% of women with hirsutism had hyperprolactinemia, 4 or 3% had PCOS with a combined etiology with NC-CAH, 2 or 1.5% had HAIR-AN syndrome, hyper or hypothyroidism 2 or 1.5%, while 1 or 0.7% had metabolic syndrome, diabetes type I and diabetes type II (Table 1).

To evaluate hirsutism, we used the Ferriman-Gallwey scoring system in 11 androgen-sensitive areas. According to the standard deviation, the Ferriman-Gallwey scale was changed the most in women with PCOS (26.7 ±7.2), than in those with congenital adrenal hyperplasia, and the least in women with idiopathic hirsutism (20.4 ±4.8).

Infertility was present in 19 (14.0%) cases, mainly in women with PCOS and hyperandrogenemia. There was no significant difference between different etiological groups (p = 0.941). In these women, the level of progesterone in the luteal phase was below the normal level. Infertility was present with a higher percentage in women with idiopathic hyperandrogenemia and PCOS, and was the least present in women with idiopathic hirsutism. After receiving the therapy, 11 or 8.1% became pregnant and gave birth to children.

Only 37 women or 27.4% were not prescribed any therapy, combined oral contraceptive (Diane 35) was prescribed to 45 women or 33.3% (in 30 cases, Diane 35 was prescribed only and in 15 cases in combination with other medications). Dexamethasone was prescribed to 41 women or 30.4% (in 9 cases, dexamethasone was prescribed alone and in 32 cases in combination with other medications). Oral diabetes medicine (metformin) was prescribed to 38 women or 28.1% (in 3 cases, metformin was prescribed alone and in 35 cases in combination with other medications). Other therapies were prescribed less frequently (Table 2).

In our experimental group, only one female used 5α-reductase inhibitors and had a significant improvement in hirsutism, acne and menstrual cycle, without side effects.

In 31 women with hirsutism or 23%, laser was applied (Table 3).

Women with hirsutism, for face hair removal, most often used laser in 31 cases or 23%, then tweezers 28 or 20.7%, 21 or 15.6% depilatory cream, while other methods were less represented.

On the body, the most frequent method of depilation was the razor in 45 cases or 33.3%, then wax in 37 cases or 27.4%, the other methods were less represented (Table 4).

After 1 year of therapy, 57 or 42.2% of women with hirsutism had a significant improvement, 29 or 21.5% had a little improvement, and 49 or 36.3% had no improvement. In acne, 12 or 8.9% of women with hirsutism had a significant improvement, 7 or 5.2% had a little improvement and 13 or 9.6% had no improvement in acne. In 11 women or 8.1% the menstrual cycle was made regular, 11 or 8.1% became pregnant or gave birth and only one or 0.7% continued to have amenorrhea. 11 or 8.1% of women experienced weight loss (Table 5).

Discussion

Hirsutism is a medical condition characterized by excessive hair growth in women in areas where typically thicker, darker hair grow, such as the face, chest, and back [24]. Women with hirsutism may feel self-conscious about their appearance. The visible hair growth in areas like the face, chest, or back can lead to negative body image and dissatisfaction with their physical appearance [25]. This can significantly affect self-esteem, with some women feeling less feminine or attractive, which may contribute to low confidence [26]. Persistent concerns about how others perceive them can lead to anxiety and, in some cases, depression. Women with hirsutism may avoid social situations where their hair growth could be exposed [27]. Addressing hirsutism and providing effective treatment is crucial for both the physical and psychological well-being of those affected [28]. Emphasizing the significance of treating this condition requires recognizing the profound impact it can have on a person’s quality of life, and understanding the multiple layers of suffering it can cause [29].

This article explores various treatment options for hirsutism, examining their effectiveness, potential side effects, and suitability for different patients. Treatment can vary depending on the underlying cause and severity.

The primary cause of hirsutism is often an imbalance in androgens [30]. In a condition like PCOS, excess production of these hormones leads to development of male-pattern hair growth in women. Other causes include adrenal disorders, certain medications, and genetic factors [31].

More frequently used medications for hirsutism that reduce the level of androgens are oral contraceptives, because they simultaneously treat hirsutism, acne and menstrual cycle disorders. Oral contraceptives containing low doses of ethinyl estradiol and progestin medication (desogestrel) are effective in controlling hyperandrogenemia and hirsutism and improve the metabolic profile in women with hirsutism, also help improve acne and regulate the menstrual cycle [32]. Oral contraceptives can be combined with antiandrogens to treat hirsutism [33]. Over 75% of women have shown improvement in hirsutism with combination therapy, but the data show that combination therapy is not significantly better than a single drug. Improvement of hirsutism after using oral contraceptives alone or in combination with other medications has given similar results.

Anti-androgens like spironolactone are also effective as they block androgen receptors on hair follicles. By doing this, spironolactone reduces the stimulation that these male hormones would normally give to hair growth, especially in areas sensitive to these hormones [34]. Spironolactone also reduces the production of testosterone from the ovaries and adrenal glands, which contributes to the hormonal imbalance that causes hirsutism [35]. By blocking androgens and lowering testosterone levels, spironolactone makes the hair follicles less sensitive to the hormone, leading to less excessive hair growth [36].

A 5'-reductase inhibitor has been observed to be very effective in the treatment of hirsutism with relatively few side effects. It works by inhibiting an enzyme called 5α-reductase, which converts testosterone into dihydrotestosterone (DHT). DHT is the hormone responsible for many of the symptoms of conditions like hair loss and hirsutism, as it can stimulate the growth of male-pattern hair in areas like the face and body. By lowering the levels of DHT, 5α-reductase inhibitor can help reduce hair growth in areas that are affected by hirsutism, such as the face, chest, and back [37]. The response to the effect of antiandrogens is slow and takes longer than 18 months [38]. The duration of therapy is unclear, but discontinuation of therapy is always followed by regrowth of terminal hair, which has been observed in a number of women.

Insulin-sensitizing drugs like metformin improves insulin sensitivity and reduces testosterone levels in women with PCOS [39]. An improvement in the clinical manifestation of hyperandrogenemia has been observed after the use of metformin for 3 months. Lyndal Harborne’s prospective, randomised trial has shown that metformin is the most effective treatment for moderate to severe hirsutism in women with PCOS [40, 41].

Dexamethasone has mainly been used for the treatment of non-classic congenital adrenal hyperplasia (NC CAH), using low doses of dexamethasone in the evening [42].

Medical treatment for hirsutism is never curative and therefore should be administered for the long term. The PCOS adolescents and women must be counselled that the effect of medical treatment is evident only after several months and therefore requires monitoring by an expert while on treatment [9, 43].

Lifestyle changes, including weight management and regular exercise, can have a significant impact on managing hirsutism, especially in patients with PCOS. Reducing body fat can lower androgen levels, and a healthy diet may help in regulating insulin sensitivity, further improving symptoms [44].

There are various methods of cosmetic treatment of hirsutism, which remove the hair from the surface or remove it by the roots. Different techniques for managing hirsutism include bleaching, waxing with a razor, tweezers, waxing, electrolysis and the use of lasers, but possible complications such as: skin irritation, secondary infections, dermatitis, folliculitis, hyperpigmentation should be taken into account, hypopigmentation, transmission of hepatitis B, herpes simplex, and AIDS may occur if unsterilized electrolysis needles are used [45].

There are different types of lasers: ruby, alexandrite, pulsed diode, Q-switched yttrium-aluminium-garnet (YAG). Pulsed diode laser is cheaper and more reliable [46].

Q-switched YAG lasers work best on dark skin, however these lasers are ineffective for long-term hair removal [47].

In most women hair growth is delayed for 2 to 6 months after the first treatment, while others remove hair permanently after several treatments [48]. Laser treatment is successful when the hair is dark, although hyperpigmentation may develop after treatment [49].

Laser treatment not only reduces dark hair but also improves depression and anxiety in women with hirsutism [50].

In many women, hirsutism can be controlled with laser alone, without using drug therapy. However, they come with higher upfront costs and may require multiple sessions [4, 51].

Surgical treatment, like ovarian drilling is a surgical procedure that involves making small incisions in the ovaries to reduce androgen production. It is generally considered when other treatments have failed, but it carries risks such as ovarian damage and infertility concerns [52].

Considering mental well-being when deciding on the treatment of hirsutism is crucial for several reasons [53]. Many people with hirsutism experience low self-esteem, embarrassment, and social anxiety. These feelings can contribute to mental health conditions like depression and anxiety. Treatment that helps address the physical symptoms can help improve a person’s self-image, leading to better mental well-being [54]. Many treatments for hirsutism, such as oral contraceptives or spironolactone, have potential side effects that can affect mental health [55]. For instance, hormonal treatments may cause mood swings, depression, or anxiety in some individuals [56].

Treating the physical symptoms of hirsutism without addressing the potential mental health consequences can lead to long-term psychological distress [57]. It is important for healthcare providers to discuss both the physical and emotional aspects of the condition to ensure a comprehensive approach to well-being [58].

Conclusions

Treating hirsutism requires a multifaceted approach that takes into account the underlying cause, the severity of the condition, and the patient’s preferences.

While medical and physical treatments can provide relief, a holistic approach that includes lifestyle changes and mental health support is crucial. Early intervention and regular monitoring can prevent progression and provide significant relief. Ongoing research continues to offer hope for more effective, tailored therapies in the future.