Treatment of HH may consist of administration of either a GnRH agonist or a gonadotropin formulation in the case of primary HH and treatment of the root cause (e.g., a tumor) of the symptoms in the case of secondary HH. Alternatively, hormone replacement therapy with androgens and estrogens in males and females, respectively, may be employed.

The aim for hormone replacement therapy (HRT) for both men and women is to ensure that the level of circulating hormones (testosterone for men and oestrogen/progesterone for women) is at the normal physiological level for the age of the patient. At first the treatment will produce most of the physical and psychological changes seen at puberty, with the major exception that there will be no testicular development in men and no ovulation in women.

After the optimum physical development has been reached HRT for men will continue to ensure that the normal androgen function is maintained; such as libido, muscle development, energy levels, hair growth, and sexual function. In women, a variety of types of HRT will either give a menstruation cycle or not as preferred by the patient. HRT is very important in both men and women to maintain bone density and to reduce the risk of early onset osteoporosis.

The fertility treatments used for both men and women would still include hormone replacement in their action.

There are a range of different preparations available for HRT for both men and women; a lot of these, especially those for women are the same used for standard HRT protocols used when hormone levels fall in later life or after the menopause.

For males with KS / CHH the types of delivery method available include daily patches, daily gel use, daily capsules, sub cutaneous or intramuscular injections or six monthly implants. Different formulations of testosterone are used to ensure both the anabolic and androgenic effects of testosterone are achieved.

Testosterone undecanoate is commonly used worldwide, though less so in the US, for treating male KS / CHH patients and has proved to be effective in maintaining good testosterone levels with an increased injection period of up to 12 weeks.

The precise treatment method used and interval between injections will vary from patient to patient and may need to be adjusted to maintain a physiological normal level of testosterone over a longer period of time to prevent the mood swings or adverse effects that can occur if testosterone levels are too high or low. Some treatments may work better with some patients than others so it might be a case of personal choice as which one to use.

As an alternative human chorionic gonadotrophin (hCG) can also be used to stimulate natural testosterone production. It acts in the same way as LH; stimulating the Leydig cells in the testes to produce testosterone. hCG can be used as pre-cursor to male fertility treatments but it can be used in isolation just for testosterone production.

There are no specialist HRT treatments available just for women with KS/HH but there are multitude of different HRT products on the market including oral contraceptives and standard post-menopause products. Pills are popular but patches are also available. It may take some trial and error to find the appropriate HRT for the patient depending on how her body reacts to the particular HRT. Specialist medical advice will be required to ensure the correct levels of oestrogen and progesterone are maintained each month, depending on whether the patient requires continuous HRT (no-bleed) or a withdrawal option to create a "menstrual" type bleed. This withdrawal bleed can be monthly or over longer time periods depending on the type of medication used.

Hormone replacement therapy with estrogen may be used to treat symptoms of hypoestrogenism in females with the condition. There are currently no known treatments for the infertility caused by the condition in either sex.

Medications consist mostly of antiandrogens, drugs that block the effects of androgens like testosterone and dihydrotestosterone (DHT) in the body, and include:

- Spironolactone: An antimineralocorticoid with additional antiandrogenic activity at high dosages

- Cyproterone acetate: A dual antiandrogen and progestogen. In addition to single form, it is also available in some formulations of combined oral contraceptives at a low dosage (see below). It has a risk of liver damage.

- Flutamide: A pure antiandrogen. It has been found to possess equivalent or greater effectiveness than spironolactone, cyproterone acetate, and finasteride in the treatment of hirsutism. However, it has a high risk of liver damage and hence is no longer recommended as a first- or second-line treatment.

- Bicalutamide: A pure antiandrogen. It is effective similarly to flutamide but is much safer as well as better-tolerated.

- Birth control pills: Consist of an estrogen, usually ethinylestradiol, and a progestin. They are thought to work by 1) stimulating production of sex hormone-binding globulin in the liver, which decreases free concentrations of testosterone in the blood; and by 2) suppressing luteinizing hormone (LH) secretion from the pituitary gland, which decreases production of testosterone by the gonads. Hence, they are functional antiandrogens. In addition, certain birth control pills contain a progestin that also has antiandrogenic activity. Examples include birth control pills containing cyproterone acetate, chlormadinone acetate, drospirenone, and dienogest.

- Finasteride and dutasteride: 5α-Reductase inhibitors. They inhibit the production of the potent androgen DHT.

- GnRH analogues: Suppress androgen production by the gonads and reduce androgen concentrations to castrate levels.

- Metformin: Antihyperglycemic drug used for diabetes mellitus. However, it is also effective in treatment of hirsutism associated with insulin resistance (e.g. polycystic ovary syndrome)

- Eflornithine: Blocks putrescine that is necessary for the growth of hair follicles

In cases of hyperandrogenism specifically due to congenital adrenal hyperplasia, administration of glucocorticoids will return androgen levels to normal.

Males and females may be treated with hormone replacement therapy (i.e., with androgens and estrogens, respectively), which will result in normal sexual development and resolve most symptoms. In the case of 46,XY (genetically male) individuals who are phenotypically female and/or identify as the female gender, they should be treated with estrogens instead. Removal of the undescended testes should be performed in 46,XY females to prevent their malignant degeneration, whereas in 46,XY males surgical correction of the genitals is generally required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well. Namely in genetic females presenting with ovarian cysts, GnRH analogues may be used to control high FSH and LH levels if they are unresponsive to estrogens.

Treatment for KS and other forms of HH can be divided into hormone replacement therapy and fertility treatments.

One possible treatment is with anastrozole. Histrelin acetate (Supprelin LA), triptorelin or leuprolide, any GnRH agonists, may be used. Non-continuous usage of GnRH agonists stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). However, when used regularly, GnRH agonists cause a decreased release of FSH and LH. Prolonged use has a risk of causing osteoporosis. After stopping GnRH agonists, pubertal changes resume within 3 to 12 months.

XX females with lipoid CAH may need estrogen replacement at or after puberty. Active intervention has been used to preserve the possibility of fertility and conception in lipoid CAH females. In a case report in 2009, a woman with late onset lipoid CAH due to StAR deficiency underwent hormone replacement therapy in combination with an assisted fertility technique, intracytoplasmic sperm injection. This led to ovulation and with implantation of the in vitro fertilized egg, a successful birth.

Diagnosis of cortisone reductase deficiency is done through analysis of cortisol to cortisone metabolite levels in blood samples. As of now, there is no treatment for cortisone reductase deficiency. Shots of cortisol are quickly metabolised into cortisone by the dysregulated 11β-HSD1 enzyme; however, symptoms can be treated. Treatment of hyperandroginism can be done through prescription of antiandrogens. They do so by inhibiting the release of gonadotropin and luteinizing hormone, both hormones in the pituitary, responsible for the production of testosterone.

Treatment of HH is usually with hormone replacement therapy, consisting of androgen and estrogen administration in males and females, respectively.

When appropriate (e.g., in women of child-bearing age who require contraception), a standard contraceptive pill is frequently effective in reducing hirsutism. Progestogens such as norgestrel and levonorgestrel should be avoided due to their androgenic effects.

Other drugs with anti-androgen effects include flutamide, and spironolactone, which can give some improvement in hirsutism. Metformin can reduce hirsutism, perhaps by reducing insulin resistance, and is often used if there are other features such as insulin resistance, diabetes, or obesity that should also benefit from metformin. Eflornithine (Vaniqa) is a drug that is applied to the skin in cream form, and acts directly on the hair follicles to inhibit hair growth. It is usually applied to the face. 5-alpha reductase inhibitors (such as finasteride and dutasteride) may also be used; they work by blocking the conversion of testosterone to dihydrotestosterone (the latter of which responsible for most hair growth alterations and androgenic acne).

Although these agents have shown significant efficacy in clinical trials (for oral contraceptives, in 60–100% of individuals), the reduction in hair growth may not be enough to eliminate the social embarrassment of hirsutism, or the inconvenience of plucking or shaving. Individuals vary in their response to different therapies. It is usually worth trying other drug treatments if one does not work, but drug treatments do not work well for all individuals.

A 2017 review concluded that while both myo-inositol and D-chiro-inositols may regulate menstrual cycles and improve ovulation, there is a lack of evidence regarding effects on the probability of pregnancy. A 2012 and 2017 review have found myo-inositol supplementation appears to be effective in improving several of the hormonal disturbances of PCOS. A 2011 review found not enough evidence to conclude any beneficial effect from D-chiro-inositol. There is insufficient evidence to support the use of acupuncture.

Patients with Leydig cell hypoplasia may be treated with hormone replacement therapy (i.e., with androgens), which will result in normal sexual development and the resolution of most symptoms. In the case of 46,XY (genetically "male") individuals who are phenotypically female and/or identify as the female gender, estrogens should be given instead. Surgical correction of the genitals in 46,XY males may be required, and, if necessary, an orchidopexy (relocation of the undescended testes to the scrotum) may be performed as well.

Many women with unwanted hair seek methods of hair removal. However, the causes of the hair growth should be evaluated by a physician, who can conduct blood tests, pinpoint the specific origin of the abnormal hair growth, and advise on the treatment.

Medical treatment of gynecomastia is most effective when done within the first two years after the start of male breast enlargement. Selective estrogen receptor modulators (SERMs) such as tamoxifen, raloxifene, and clomifene may be beneficial in the treatment of gynecomastia but are not approved by the Food and Drug Administration for use in gynecomastia. Clomifene seems to be less effective than tamoxifen or raloxifene. Tamoxifen may be used for painful gynecomastia in adults. Aromatase inhibitors (AIs) such as anastrozole have been used off-label for cases of gynecomastia occurring during puberty but are less effective than SERMs. A few cases of gynecomastia caused by the rare disorders aromatase excess syndrome and Peutz–Jeghers syndrome have responded to treatment with AIs such as anastrozole. Androgens/anabolic steroids may be effective for gynecomastia. Testosterone itself may not be suitable to treat gynecomastia as it can be aromatized into estradiol, but non-aromatizable androgens like topical androstanolone (dihydrotestosterone) can be useful.

Treatment may consist of surgery in the case of tumors, lower doses of estrogen in the case of exogenously-mediated estrogen excess, and estrogen-suppressing medications like gonadotropin-releasing hormone analogues and progestogens. In addition, androgens may be supplemented in the case of males.

If chronic gynecomastia is treated, surgical removal of glandular breast tissue is usually required. Surgical approaches to the treatment of gynecomastia include subcutaneous mastectomy, liposuction-assisted mastectomy, laser-assisted liposuction, and laser-lipolysis without liposuction. Complications of mastectomy may include hematoma, surgical wound infection, breast asymmetry, changes in sensation in the breast, necrosis of the areola or nipple, seroma, noticeable or painful scars, and contour deformities.

Variable success rate with treatment, very few controlled studies, mostly case reports. Treatment success strongly tends to diminish with age and degree of elevation of FSH.

- Donor oocyte. Oocyte donation is the most successful method for producing pregnancy in perimenopausal women. In the UK the use of donor oocytes after natural menopause is controversial. A 1995 study reported that women age fifty or higher experience similar pregnancy rates after oocyte donation as younger women. They are at equal risk for multiple gestation as younger women. In addition, antenatal complications were experienced by the majority of patients, and that high risk obstetric surveillance and care is vital.

- Natural or Mini-IVF, but without the use of hCG to trigger ovulation, instead the GnRH agonist Synarel (nafarelin acetate) in a diluted form is taken as a nasal spray to trigger ovulation. Human chorionic gonadotropin (hCG) has a long half life and may stimulate (luteinize) small follicles prematurely and cause them to become cysts. Whereas nafarelin acetate in a nasal spray induces a short lived LH surge that is high enough to induce ovulation in large follicles, but too short lived to adversely affect small follicles. This increases the likelihood of the small follicles and oocytes therein developing normally for upcoming cycles and also allows the woman to cycle without taking a break and consequently increases the probability of conception in poor ovarian reserve women and advanced reproductive aged women.

- Pretreatment with 50 mcg ethinylestradiol three times a day for two weeks, followed by recombinant FSH 200 IU/day subcutaneously. Ethinylestradiol treatment was maintained during FSH stimulation. When at least one follicle reached 18mm in diameter and serum estradiol was greater or equal to 150 pg/ML ovulation was induced with an intramuscular injection of 10,000 IU of hCG (human chorionic gonadotropin hormone). For luteal phase support 5,000 IU of hCG was administered every 72 hours. Out of 25 patients 8 ovulated and 4 became pregnant. In the control group there were no ovulations. The patients ranged in age between 24 and 39 years with an average age of 32.7. All women had amenorrhea for at least 6 months (average 16.75 months) and FSH levels greater or equal than 40 mIU/mL (average FSH 68 mIU/ML). The researchers believe this protocol would work for women in early post menopause as well.

- Ethinylestradiol or other synthetic estrogens along with luteal phase progesterone (twice daily 200 mg vaginal suppositories) and estradiol support. Ethinylestradiol lowers high FSH levels which then, it is theorized, up regulates FSH receptor sites and restores sensitivity to FSH. Ethinylestradiol also has the advantage that it does not interfere with the measurement of serum levels of endogenous estradiol. During the luteal phase the FSH levels should be kept low for subsequent cycles, thus the phase is supplemented with 4 mg oral estradiol. Since conception may have occurred estradiol is used instead of the synthetic ethinylestradiol.

- Cyclical hormone replacement therapy.

- The following protocols have shown promise: high dose gonadoropins, flare up GnRH-a protocol (standard or microdose), stop protocols, short protocol, natural cycle or modified natural cycle and low dose hCG during the beginning of the stimulation protocol.

- Gonadotropin-releasing hormone agonist/antagonist conversion with estrogen priming (AACEP) protocol. Fisch, Keskintepe and Sher report 35% (14 out of 40) ongoing gestation in women with elevated FSH levels (all women had prior IVF and poor quality embryos); among women aged 41–42 the ongoing gestation rate was 19% (5 out of 26).

- DHEA: Recent clinical trial by the Center for Human Reproduction in New York showed significant effectiveness. Leonidas and Eudoxia Mamas report six cases of premature ovarian failure. After two to six months of treatment with DHEA (Two 25 mg capsules daily in five cases and three 25 mg capsules daily in one case.) all women conceived. One delivered via C-section, one aborted at 7 weeks and the remaining four were reported at 11 to 27 weeks gestation. Ages were from 37 to 40. FSH levels were from 30 to 112 mIU/mL. Ammenorhea ranged from 9 to 13 months. In addition, there is strong evidence that continuous micronized DHEA 25 mg TID reduces miscarriage and aneuploidy rates, especially above age 35.

- Glucocorticoid therapy. A recent (2007) randomized double blind study done in Egypt reported a statistically significant theurapeutic effect with dexamethasone pretreatment. Fifty-eight women with idiopathic premature ovarian failure and normal karyotype were divided into two groups of twenty-nine. The control group received placebo for twenty-eight days and then GnRH agonists plus gonadotropin therapy (hMG). The treatment group received dexamethasone for twenty-eight days (6 mg/ day) and then GnRH agonists plus gonadotropin therapy (hMG). (In both groups after the first twenty-eight days, and concurrent with the GnRH agonist treatment, the placebo or dexamethasone was gradually tapered off over ten days.) The treatment group had six ovulations and two pregnancies (p value of .02). The control group had three ovulations and no pregnancies.

- A combined pentoxifylline-tocopherol treatment has been reported effective in improving uterine parameters in women with POF undergoing IVF with donor oocytes (IVF-OD). Three women with uterine hormonoresistance despite high estradiol (E2) plasma levels received treatment with 800 mg pentoxifylline and 1000 IU of vitamin E for at least nine months. Three frozen-thawed embryo transfers (ETs) resulted in two viable pregnancies. Mean endometrial thickness increased from 4.9 mm (with thin uterine crosses) to 7.4 mm with nice uterine crosses. This treatment protocol has also reversed some cases of iatrogenic POF caused by full body radiation treatment.

Management of salt-wasting crises and mineralocorticoid treatment are as for other forms of salt-wasting congenital adrenal hyperplasias: saline and fludrocortisone.

Glucocorticoids can be provided at minimal replacement doses because there is no need for suppression of excessive adrenal androgens or mineralocorticoids. As with other forms of adrenal insufficiency, extra glucocorticoid is needed for stress coverage.

Pre- and post-testicular azoospermia are frequently correctible, while testicular azoospermia is usually permanent. In the former the cause of the azoospermia needs to be considered and it opens up possibilities to manage this situation directly. Thus men with azoospermia due to hyperprolactinemia may resume sperm production after treatment of hyperprolactinemia or men whose sperm production is suppressed by exogenous androgens are expected to produce sperm after cessation of androgen intake. In situations where the testes are normal but unstimulated, gonadotropin therapy can be expected to induce sperm production.

A major advancement in recent years has been the introduction of IVF with ICSI which allows successful fertilization even with immature sperm or sperm obtained directly from testicular tissue. IVF-ICSI allows for pregnancy in couples where the man has irreversible testicular azoospermia as long as it is possible to recover sperm material from the testes. Thus men with non-mosaic Klinefelter's syndrome have fathered children using IVF-ICSI. Pregnancies have been achieved in situations where azoospermia was associated with cryptorchism and sperm where obtained by testicular sperm extraction (TESE).

In men with posttesticular azoospermia a number of approaches are available. For obstructive azoospermia IVF-ICSI or surgery can be used and individual factors need to be considered for the choice of treatment. Medication may be helpful for retrograde ejaculation.

Most people develop symptoms of estrogen deficiency, including vasomotor flushes and vaginal dryness, both of which respond to hormone replacement therapy. There are several contraindications of estrogen supplement, including smokers over 35 years of age, uncontrolled hypertension, uncontrolled diabetes mellitus, or history of thromboemboli events.

Women younger than 40 year with primary ovarian insufficiency benefit from physiologic replacement of hormones. Most authorities recommend that this hormone replacement continue until age 50 years, the normal age of menopause. The leading hormone replacement regimen recommended involves the administration of estradiol daily by either skin patch or vaginal ring. This approach reduces the risk of pulmonary embolism and deep venous thrombosis by avoiding the first pass effect on the liver that is induced by oral estrogen therapy. To avoid the development of endometrial cancer young women taking estradiol replacement need also to take a progestin in a regular cyclic fashion. The most evidence supports the use of medroxyprogesterone acetate per day for days one through 12 of each calendar month. This will induce regular and predictable menstrual cycles. It is important that women taking this regimen keep a menstrual calendar. If the next expected menses is late it is important to get a pregnancy test. It this is positive, the woman should stop taking the hormone replacement. Approximately 5 to 10% of women with confirmed primary ovarian insufficiency conceive a pregnancy after the diagnosis without medical intervention.

The transdermal estradiol patch is commonly recommended due to several advantages. It provides the replacement by steady infusion rather than by bolus when taking daily pills. It also avoids the first-pass effect in the liver.

Testosterone has been used to successfully treat undervirilization in some but not all men with PAIS, despite having supraphysiological levels of testosterone to start with. Treatment options include transdermal gels or patches, oral or injectable testosterone undecanoate, other injectable testosterone esters, testosterone pellets, or buccal testosterone systems. Supraphysiological doses may be required to achieve the desired physiological effect, which may be difficult to achieve using non-injectable testosterone preparations. Exogenous testosterone supplementation in unaffected men can produce various unwanted side effects, including prostatic hypertrophy, polycythemia, gynecomastia, hair loss, acne, and the suppression of the hypothalamic-pituitary-gonadal axis, resulting in the reduction of gonadotropins (i.e., luteinizing hormone and follicle-stimulating hormone) and spermatogenic defect. These effects may not manifest at all in men with AIS, or might only manifest at a much higher concentration of testosterone, depending on the degree of androgen insensitivity. Those undergoing high dose androgen therapy should be monitored for safety and efficacy of treatment, possibly including regular breast and prostate examinations. Some individuals with PAIS have a sufficiently high sperm count to father children; at least one case report has been published that describes fertile men who fit the criteria for grade 2 PAIS (micropenis, penile hypospadias, and gynecomastia). Several publications have indicated that testosterone treatment can correct low sperm counts in men with MAIS. At least one case report has been published that documents the efficacy of treating a low sperm-count with tamoxifen in an individual with PAIS.

Finasteride is a medication of the 5α-reductase inhibitors (5-ARIs) class. By inhibiting type II 5-ARI, finasteride prevents the conversion of testosterone to dihydrotestosterone in various tissues including the scalp. Increased hair on the scalp can be seen within three months of starting finasteride treatment and longer-term studies have demonstrated increased hair on the scalp at 24 and 48 months with continued use. Treatment with finasteride more effectively treats male-pattern hair loss at the vertex than male-pattern hair loss at the front of the head and temples.

Dutasteride is a medication in the same class as finasteride but inhibits both type I and type II 5-alpha reductase. Dutasteride is approved for the treatment of male-pattern hair loss in Korea and Japan, but not in the United States. However, it is commonly used off-label to treat male-pattern hair loss.

Several treatments have been found to be effective in managing AES, including aromatase inhibitors and gonadotropin-releasing hormone analogues in both sexes, androgen replacement therapy with non-aromatizable androgens such as DHT in males, and progestogens (which, by virtue of their antigonadotropic properties at high doses, suppress estrogen levels) in females. In addition, male patients often seek bilateral mastectomy, whereas females may opt for breast reduction if warranted.

Medical treatment of AES is not absolutely necessary, but it is recommended as the condition, if left untreated, may lead to excessively large breasts (which may necessitate surgical reduction), problems with fertility, and an increased risk of endometriosis and estrogen-dependent cancers such as breast and endometrial cancers later in life. At least one case of male breast cancer has been reported.

Hair loss can be slowed or reversed in its early stages with medication. Medications approved by the United States' Food and Drug Administration (FDA) to treat male-pattern hair loss include minoxidil and finasteride.