Women’s Issues With Hepatitis C - Side Effect Management

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Women’s Issues With Hepatitis C - Side Effect Management

Hepatitis C (HCV) affects women differently than men. Women, especially if they were young at the time of acquiring the virus, are less likely than men to progress from acute to chronic HCV. Thus, women have a higher rate of spontaneous viral clearance than men. And, women, especially premenopausal women, appear to progress to cirrhosis less often then men. In fact, studies have shown that women with HCV have only a 5 percent likelihood of progressing to cirrhosis, as compared with a 20-30 percent likelihood for men. In addition, many studies have found that men are as much as four times more likely than women to develop liver cancer due to HCV. Finally, women appear to be better responders to therapy with pegylated interferon plus ribavirin. Thus, women with HCV are cured a greater percentage of the time than men. While these differences between men and women are well documented, many issues pertaining specifically to women undergoing therapy for HCV have not been

extensively studied.

Overall, women on pegylated interferon plus ribavirin experience side effects more frequently than men. Women more frequently suffer from fatigue, headaches, depression, anxiety, irritability and insomnia. However, in this article, I will concentrate on some cosmetic concerns, sexual problems, menstrual irregularities, and bone loss problems that women with HCV may encounter while on antiviral therapy. I will also discuss some helpful ways to diminish these potential side effects or to prevent them from occurring in the first place.

COSMETIC SIDE EFFECTS

There are many cosmetic side effects that may occur while on antiviral therapy. In general, women appear to be more concerned than men about these potential side effects. These issues will now be discussed.

Hair Loss

Interferon can cause hair thinning, hair loss, hair breakage, and can change the texture of hair. However, some women are under the impression that interferon therapy will cause them to lose all their hair. (Well, that’s what Pamela stated as one of her main reasons for not starting therapy!). This is a total misconception. In fact, hair loss while on interferon therapy is infrequent. If it occurs at all, the amount of hair lost is often minimal and usually unnoticeable to others. Women on interferon do not experience hair loss in the way that a cancer patient on chemotherapy does. Hair loss from interferon appears to be most frequent in Caucasians with black hair, and in Orientals. It typically occurs around the third or fourth month of therapy. Hair loss may continue for up to three months after treatment is discontinued. Hair loss is more common among women then it is among men (as well as less socially acceptable).

If hair loss does occur, there are many steps that women can take to minimize this side effect. Women should refrain from dying or bleaching their hair while on interferon therapy, since this may exacerbate hair loss. A mild hair rinse may be used as an alternative to coloring. Avoid permanents and hair straightening procedures while on therapy. Many women have found the vitamin biotin (a B vitamin) to be helpful. It is advisable to take this vitamin daily a few weeks prior to beginning therapy and to continue while on therapy. A mild shampoo and a detangling conditioner are advisable. Nioxin shampoo, Nioxin conditioner and Nioxin hair growth promoter can help keep hair loss to a minimum while on therapy. Nioxin hair loss treatment should be started about a month prior to starting antiviral therapy. Other recommended shampoos include Tricomin, Revivogen and Nizoral. Minoxidil (Rogaine) liquid topical medication may be of some

benefit. It should be applied only to the scalp and not ingested. It may stop hair loss and thicken the remaining hair, but continued use twice daily for at least 4 months is typically required before obvious results are noted.

Other tips for diminishing hair loss include: the use of a wide tooth comb, avoidance of curling irons and rollers, and avoidance of daily shampooing. Avoid cornrowing, tight braids and pulling hair back in a ponytail with tight rubberbands. A short haircut may be in order. If hair loss becomes a major problem, medical insurances will typically cover the cost of a wig or a hairpiece. Often a doctor’s note or prescription along with a receipt of purchase is all that is required for insurance reimbursement.

Fortunately, any hair loss induced by interferon therapy is temporary, and regrowth typically occurs within three to six months from the drug’s discontinuation. The color and texture of hair may differ from the person’s original hair type. In fact, many women have noted that their hair grows back thicker, straighter, and shinier than before!

Brittle nails

Women often have frequent breaking, cracking and splitting of nails while on interferon. Anemia, thyroid abnormalities, dehydration, weight loss and poor nutrition all of which can occur on interferon, should be eliminated as possible contributing factors, and corrected if discovered. Constant nail biting may be a sign of interferon –induced anxiety. A SSRI may be in order under these circumstances. Gloves should be worn when doing dishes. Nails should be cut short, and nail salons and nail polish remover should be avoided. Petroleum jelly (Vaseline) or olive oil holds the moisture around the nails and decreases breakage. Biotin, zinc and/or glucosamine chondroitin may afford some decrease in breakage, but this has not been proven.

Dermatologic Side Effects

Skin problems (rashes, itching, and dry skin) occur in 10-30 percent of women undergoing combination therapy, and are primarily caused by ribavirin.

Rashes

Rashes may occur anywhere on the body but are most common in sun-exposed areas and at the injection sites. Therefore, it is important to protect the skin from direct sunlight.

Sunbathing should be totally avoided while on therapy, as severe sunburns may occur. Tanning beds should also be avoided. A sunscreen with an SPF of 30 or more must be applied to the face and any other exposed areas prior to going outside during daylight hours. In addition, women should where makeup containing a sunscreen with an SPF of 15 or higher. A hat with a brim is important to wear if going outdoors between 10 AM and 3 PM. Women who are prone to rashes, should take an antihistamine such as benadryl 1/2 hour before taking ribavirin. And, either benadryl lotion or hydrocortisone lotion applied directly to a rash usually provides relief.

Itching

Some women find relief from itching by using gentle anti-itching soaps and lotions made for sensitive skin such as Aveeno, Cetaphil soap, L’Occitane or other brands containing an oatmeal base. Over-the-counter topical hydrocortisone cream or Benadryl lotion may be applied directly to the itchy area. It is important to avoid perfumed soaps and lotions.

Hot baths and showers have been noted to exacerbate itching and should be avoided. Instead, take lukewarm baths and showers. It is important for women suffering with itching to wear loose fitting clothes made of soft, smooth cotton (not wool) material and to keep their skin as moisturized as possible. Drinking up to one gallon of bottled water each day has also found to be helpful. During hot and humid weather, women who suffer from itching are advised to stay indoors in air-conditioned places. Finally, oral antihistamines such as Benadryl or Claritin may be used.

Dry skin

In addition to drinking about one gallon of water per day, women who suffer from dry skin are advised to use a topical moisturizer with low water content such as Lachydrin (ammonium lactate) 12 percent lotion or Aquaphor. Lachydrin tends to keep the skin well hydrated, as it helps the skin hold water. This lotion requires a prescription from the doctor. Aquaphor is an over-the counter ointment, that is helpful to protect particularly dry, chafed skin and lips. Finally, bathing or showering less often, and using warm, rather than hot water, in addition to using a moisturizing or hydrating body lotion will decrease skin dryness.

Dental Problems

Interferon therapy may increase the likelihood of tooth decay and dental cavities due to decreased saliva production. Saliva contains antibacterial agents which kill the bacteria that cause tooth decay. It is therefore important to take steps to increase the flow of saliva in the mouth. This can be achieved by chewing sugarless gum and by drinking fluids consistently throughout the day.

Bloodshot Eyes

Rarely, interferon may cause eye problems. Symptoms may include dry, itchy, bloodshot eyes, burning eyes, decreased vision, blurry vision, poor night vision and blind spots.

All women with high blood pressure or diabetes need to undergo an eye exam prior to beginning interferon therapy. Anyone who develops any visual disturbances while on interferon should report this symptom immediately to their doctor. Dry, itchy, bloodshot eyes may be treated with over-the–counter saline eye drops or Natural Tears. When eye problems are accompanied by decreased vision, evaluation by an ophthalmologist is necessary. In these circumstances, interferon may need to be discontinued, depending upon the severity of symptoms. Typically eye problems resolve once interferon use is stopped.

Weight Loss

Weight loss in the range of ten to twenty-five pounds may occur while a person is on pegylated interferon and ribavirin. While some women view weight loss as a beneficial side effect, others find weight loss quite distressing. Weight loss may be due to a variety of antiviral side effects including: loss of appetite, altered taste sensation, nausea, mouth sores, mouth dryness, abdominal discomfort, flatulence, and diarrhea. Weight typically returns to normal soon after therapy is discontinued. When weight loss is due to poor eating habits, women may experience vitamin and other nutritional deficiencies. This may cause or contribute to hair loss dry, thin skin, and brittle nails. In general, eating multiple – approximately six, small meals throughout the day and consuming plenty of water will help maintain a steady weight while on therapy. Large meals should always be avoided. Furthermore, the food consumed should be healthy and low in fat. Using plastic utensils

instead of metallic flatware may decrease the peculiar taste often experienced by people on therapy, and may make food more appetizing.

Nausea is more commonly a side effect of ribavirin therapy, and is typically minimized by taking ribavirin with food. Eat multiple small meals while on therapy, as large meals make nausea worse. Avoid mixing extremely cold and extremely hot foods. Fatty foods, such as red meat, as well as fried, spicy foods should also be avoided. Eat easy- to- digest foods such as crackers, broth, dry toast and jello. Ginger ale minimizes nausea.

Do not lie down after meals. However, it is important to rest after meals- but do so in a sitting or standing position. Excessive activity induces vomiting. (Remember what your mother told you – don’t go swimming on a full stomach!) Anti-nausea medications such as metoclopramide (Reglan) 10mg tablets taken orally one half hour prior to meals, as well as before going to sleep, usually relieves nausea. In situations when a person cannot tolerate anything taken oral an anti-nausea suppository such as trimethobenzamide (Tigan) 200 mg suppository taken rectally may be helpful. When nausea is particularly severe, ondansetron hydrochloride (Zofran) - an anti-nausea medication typically prescribed for cancer patients who are undergoing chemotherapy may be used. If nausea still persists, a dose reduction of ribavirin in the amount of one or two pills per day may become necessary.

Mouth sores are a common cause of decreased interest in food and subsequent weight loss. They may be due to excessive oral dryness or due to oral infections. Some women may experience a painful, burning, excessively dry or ulcerated mouth known as mucositis. Cigarette smoking worsens mucositis - another reason to get rid of this bad habit. Good oral hygiene while on pegylated interferon and ribavirin is especially important. Meticulous, but not excessive, toothbrushing (3-4 times per day) and gentle flossing are essential. If one’s gums are already injured, flossing should be avoided. The mouth should be rinsed with baking soda, rather than a commercial mouthwash, as many of these contain alcohol. It is important that any necessary dental or periodontal procedures (such as implants or dentures) should be performed at least 3-6 months prior to commencement of therapy, or 1-3 months after completion of therapy, as these procedures may worsen mouth irritation due to

antiviral therapy. Mucositis may be diminished by regularly lubricating the lips and the corners of the mouth with petroleum jelly on a regular basis, especially prior to going to sleep. A topical corticosteroid, such as fluocinomide (Lidex) 0.05%, or clobetasol (Temovate) 0.05% may enhance the healing process. A corticosteroid mouth rinse such as dexamethasone elixir may also be helpful. Xylocaine, a local anesthetic, that numbs the mouth may afford some relief. In addition, medications that coat the mouth ulcer, such as sucralfate (Carafate), Orabase – an adhesive paste with a topical anesthetic, or even kaopectate may be applied directly to the sore. This may significantly diminish the pain caused by an oral ulcer.

Mouth infections including those attributable to the herpes virus and fungal infections, such as thrush, may occur in the mouth due to a lowered white blood cell (neutropenia)- a possible side effect of pegylated interferon. Herpes simplex 1 (oral herpes) is different from herpes simplex 2 – also known as genital herpes. Oral herpes causes fever blisters or cold sores. It may be treated with acyclovir taken orally (Zovirax) or topically (Denavir). A numbing mouthwash or spray, such as Hurricane liquid, may help alleviate the pain associated with oral herpes. Oral thrush requires Mycostatin (nystatin), usually taken as a swish and swallow preparation. If this does not eradicate the fungus, Diflucan (fluconazole) tablets taken orally may be necessary.

Flatulence and diarrhea may be lessened by adhering to a lactose-free (dairy-free) diet and by avoiding raw vegetables and fruits. Vegetables may be eaten if well- cooked and fruits may be eaten provided that they are peeled first. Fiber supplements that act as bulking agents, such as Metamucil or Citrucel, may help decrease the incidence of loose stools. It is important to avoid fiber supplements containing senna, as there have been reports that some cases of toxic hepatitis have been caused by senna. Over-the-counter antidiarrheals, such as Imodium AD, may be used, but it is important to discuss any medications with your doctor prior to taking them.

Exercise in general– whether it be swimming, playing tennis, walking or weight-bearing exercises, is important while on antiviral therapy and helps stimulate one’s appetite.

If weight loss becomes severe appetite stimulants may be taken. Reglan (metoclopramide), a medication typically used in the treatment of nausea, taken 1/2 hour prior to meals may help increase the desire for food. Megace (megestrol acetate) is an appetite stimulant used to treat excessive weight loss in patients being treated with chemotherapy for cancer as well as in patients with HIV (human immunodeficiency virus – the virus that causes AIDS). Megace is similar to progesterone – a female hormone. Most weight gain associated with Megace is in the form of fat. Therefore a drawback to Megace is that it may cause nonalcoholic fatty liver disease (NAFLD) and as such, may diminish the response to antiviral treatment. Marinol, (dronabinol), also referred to as medical marijuana, has been used to stimulate appetite and to reduce the nausea and vomiting associated with chemotherapy, as well as to increase weight in people with

HIV. Studies have not been conducted on people with HCV who are on antiviral therapy. Many antidepressant/antianxiety medications such as the SSRIs (selective serotonin reuptake inhibitors) such as Paxil, Celexa, and Zoloft, as well as Ritalin have been associated with weight gain. The medications may provide a dual benefit to those on pegylated interferon and ribavirin who suffer from both depression and weight loss.

DECREASED LIBIDO

The female sex drive (libido) is a complicated combination of physical and psychological factors. Pegylated interferon plus ribavirin therapy may make women feel tired, depressed, and irritable. As a result, for many women on antiviral, sex is the last thing on their minds. Vaginal dryness can occur while on interferon. This may lead to vaginal itching, sensitivity, irritation and discomfort. Continued dryness leads to yeast infections and vaginitis- an inflamed vagina. This causes pain during sexual intercourse. Psychologically, women may feel as if they are not as attractive while on therapy. Hair may become thinner and facial skin may become drier giving the appearance of more wrinkles. All of the above results in decreased libido.

Vaginal dryness may be alleviated by using a vaginal lubricant such as K-Y Jelly or any other water-soluble lubricant that contains glycerin. Avoid using petroleum-based lubricants such as Vaseline, as they may increase the likelihood of vaginal infections. Furthermore, petroleum-based lubricants may erode and damage latex, decreasing the effectiveness of condoms. The use of vaginal gels that contains both progesterone and estrogen may need to be prescribed by one’s gynecologist. Kegel exercises (contracting the pelvic muscles) are important to do twice a day to strengthen the pelvic muscles and to increase the blood flow to the vagina (thereby naturally increasing vaginal lubrication). Vaginal fungal infections may be eradicated with mycostatin creams which are available over-the-counter.

MENSTRUAL IRREGULARITIES

Women with HCV on antiviral therapy treatment often report a variety of menstrual irregularities. And, menstrual irregularities are more common in women with cirrhosis than in women with less advanced disease Some menstrual changes that have been noted include: premature or delayed menses, decreased and prolonged menses, clotting and spotting during menstruation, and an increased incidence and intensity of premenstrual syndrome (PMS) symptoms. Menstruation typically returns to normal within 6 month of discontinuation of antiviral therapy.

It is also important to mention that since HCV can be present in menstrual blood, sanitary napkins or tampons should be placed in a leak-proof sealed bag and promptly disposed of. Also extra precautions (the use of dental dams and condoms) should be considered during and just after menstruation to decrease the chance of transmission, particularly if the sexual partner has open cuts or wounds.

OSTEOPOROSIS

Osteoporosis is a condition characterized by decreased bone mass and decreased bone density. This leads to a weakening of bones, thereby increasing the risk of bone pain and bone fractures. Some liver experts believe that ribavirin may cause or worsen osteoporosis.

Women are at higher risk for the development of osteoporosis than men. Post-menopausal women are particularly susceptible to osteoporosis because, as estrogen production stops, bone loss accelerates. In addition, women naturally have a lower percentage of muscle and bone mass than men. This further increases their risk of developing osteoporosis.

Finally, lack of activity resulting from excessive fatigue as well as poor nutritional habits while on therapy further puts women at risk for osteoporosis

All women with HCV especially postmenopausal women, and women with cirrhosis should undergo bone-mineral-density testing in order to determine whether they have osteoporosis. Blood tests, by themselves, are an insufficient means of measuring bone density and calcium requirements.

There are some steps that can be taken to reduce the likelihood of osteoporosis. Women should supplement their diets with calcium (1,000 to 2,000 milligrams per day) and vitamin D (400 to 800 IU per day). Also, an exercise routine, including weight-bearing exercises, must be incorporated into one’s lifestyle. Weight-bearing exercises not only increase muscle size, but they increase underlying bone mass, thus decreasing the likelihood of osteoporosis. Smoking, alcohol, and excessive caffeine should be avoided as these factors may worsen osteoporosis

Estrogen-hormonal therapy has been demonstrated to increase bone mass. However, oral estrogen replacement should generally be avoided in women with HCV, as it may cause additional liver problems, such as worsening of cholestasis. Furthermore, estrogen supplementation may cause certain benign liver tumors, such as hemangiomas and/or hepatic adenomas, which are more common in women to enlarge. Estrogen patches are generally a safer choice. Implantable estrogen, a recent development, is probably safe, but long-term studies as to its effect on liver disease have not been done. Soy estrogen, originally thought to be a safe alternative, should be avoided, as recent reports have suggested that it may cause drug-induced hepatitis.

Biphosphonates are phosphate derivatives that bind to the surface of the bone, thereby blocking bone removal and decreasing bone loss. Currently, there are three biphosphonates - alendronate [Fosamax], etidronate [Didronal]) and risedronate [Actonel], that have been approved by the FDA for the prevention and treatment of osteoporosis. These medications have been shown to increase bone mass, prevent bone loss, and to decrease the incidence of bone fractures. Fosamax and Actonal have the advantage of a once-a-week administration, as opposed to the alternative of daily administration. Biphosphonates should be taken on an empty stomach, along with at least 8 ounces of water. The patient should swallow the tablet while in an upright position and not lie down for 30 minutes after taking this drug. Calcium should not be taken at the same time. Women at high risk for osteoporosis with HCV with may benefit from starting biphosphonate therapy before they

develop osteoporosis. Any woman who already has osteoporosis should begin biphosphonate therapy promptly. However, women with esophageal varices should probably avoid these medications because of the drug’s capability to cause ulcers in the esophagus, which may precipitate esophageal variceal hemorrhage. Calcitonin (Miacalcin) is a hormone produced by the thyroid gland that decreases the release of calcium from the bones. Calcitonin has been shown to reduce the incidence of bone fractures and bone loss in postmenopausal women with osteoporosis. Synthetic calcitonin, known as miacalcin, is FDA approved for the treatment of osteoporosis. When sprayed into the nose, miacalcin is quickly absorbed into the blood stream. It may be also be taken as a subcutaneous injection. Miacalcin has also been shown to decrease bone pain associated with bone fractures caused by osteoporosis. In addition, it appears to be quite beneficial in preventing bone loss after liver

transplantation. Thus, miacalcin can be an effective alternative for women who do not wish to take, or are unable to take, biphosphonates.

For additional information on HCV-related women’s issues, or on managing the side effects of antiviral therapy, you may wish to consult the just-published revised edition of my book "Dr. Palmer's Guide To Hepatitis and Liver Disease". As always, continue to keep up the fight for a healthy liver.

Copyright Palmer, MD 2004 copyright ©.

[Guest guest]

Great article Liz for all women with HCV - Thank You.

Love and Hugs.

Deb