Prolactinoma and Ayurveda By: Tesia Love

by

 An Ayurvedic Interpretation and Approach to the Treatment of Prolactin-Secreting Adenoma of the Pituitary Gland

INTRODUCTION

Prolactinoma, a prolactin-secreting benign tumor (adenoma) of the anterior pituitary gland, is the most common type of pituitary tumor existing in 5 to 10 percent of the adult population1 and accounts for 30 to 40 percent of all pituitary adenomas;2, 3 however, symptomatic prolactinomas are fairly uncommon.4 In those diagnosed with symptomatic prolactinomas and consequently hyperprolactinemia (excess levels of the prolactin hormone in the blood) the condition can impact fertility, libido, vision, and neurological health in both women and men, and affect a woman’s bone health.2  Prolactinomas are four to five times more common in women than in men.5 

In a healthy, non-pathological woman prolactin, also known as luteotropic hormone or luteotropin, is responsible for the growth and development of breasts during pregnancy and the initiation and sustained production of breast milk following delivery (provided that a woman nurses).4 In men, the normal role of prolactin is unclear, but it is suspected to play a role in male fertility.6 

ETIOLOGY

Pituitary tumors, including prolactin-secreting adenomas, “develop from one single abnormal cell that multiplies into many abnormal cells, eventually forming a tumor.” 3 The cause for this development is unknown, but prolactinoma has been suspected to be caused by the genetic condition Multiple Endocrine Neoplasmia Type 1 in some patients.2 Most often, prolactinomas are considered sporadic and therefore not genetic.4 In addition, there is animal research to support speculation of the role of estrogen and xenoestrogen bisphenol-A in the development of prolactinomas.7, 8

Once a prolactin-secreting adenoma has formed, it is likely to cause hyperprolactinemia. While other conditions can cause hyperprolactinemia — such as other pituitary tumors that may block the flow of dopamine from the hypothalamus to the pituitary gland (dopamine is responsible for inhibiting prolactin in men and women), liver failure, kidney failure, some medications, stress and hypothyroidism1, 12 — prolactinomas account for about 30 percent of hyperprolactinemia cases.9

SYMPTOMS

Symptoms of prolactinoma vary for men and women and vary depending on whether or not the prolactinoma is of micro size (<10 mm) or macro size (>10 mm). Women may experience the following:2, 7

  • ● Amenorrhea (Secondary) or Oligomenorrhea (absence or irregularity of menses not associated with pregnancy or menopause)
  • ● Galactorrhea (Lactation not associated with pregnancy or recent childbirth)
  • ● Infertility
  • ● Breast Tenderness
  • ● Low Libido
  • ● Headaches, particularly between the eyebrows (More likely with macro-adenoma)
  • ● Vision Changes (More likely with macro-adenoma)

Men may experience the following symptoms as well:2, 7

  • ● Low Libido
  • ● Infertility
  • ● Gynecomastia (Enlargement of breast tissue)
  • ● Impotence
  • ● Headaches (More likely with macro-adenoma)
  • ● Vision Changes (More likely with macro-adenoma)

Normally, hypothalamic dopamine inhibits the secretion of prolactin in a woman who is not pregnant or nursing; however, high levels of prolactin in the blood due to a secreting adenoma or nipple stimulation block the secretion of dopamine and therefore prolactin levels remain elevated. High prolactin levels also inhibit the release of luteinizing hormone releasing hormone (LHRH) from the hypothalamus and therefore inhibit the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH) from the pituitary gland to the ovaries, thereby inhibiting ovulation and the menstrual cycle. Also as a result, low estrogen levels inhibit libido in women. Low LHRH secretion in men results in abnormal testicular function and therefore low testosterone levels, low libido, and decreased fertility.5

Prolactinomas greater than 10 mm in size (macroadenomas) can potentially press upon the optic nerve and/or invade the cavernous or sphenoid sinuses (location of the trigeminal nerve) causing headaches and vision changes.18 Various types of headaches are possible, including cluster headaches or short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT). Headaches are also possible in patients with prolactinoma despite tumor size.11, 19 

DIAGNOSIS

A diagnosis of prolactinoma is made with blood tests showing elevated levels of prolactin on at least two occasions. Normal prolactin levels in both men and women who are not pregnant or nursing is 0 to 20 ng/ml. Micro-adenomas are suspected with the presentation of moderately elevated levels of prolactin at 30 to 200 ng/ml. Macro-adenomas usually present prolactin levels at over 500 ng/ml.1 Diagnosis is confirmed with a magnetic resonance imaging (MRI) scan or computerized tomography (CT) scan to “define the presence of a lesion compatible with a pituitary tumor.” 12

WESTERN TREATMENT

In Western medicine, the first line of approach to treating both symptomatic micro and macro secreting-prolactinomas is dopamine agonist drugs, including bromocriptine, pergolide, quinagolide, and cabergoline. These drugs mimic dopamine, and when given at the appropriate dosage, they normalize prolactin levels. Some patients will experience not only the normalization of prolactin levels, but also tumor shrinkage as a result of the medication. Consequently, such patients may be able to decrease their dosage over time and even cease taking medication after several years of treatment; however, the tumor may grow back.12, 2 Some patients have to take dopamine agonist drugs for life in order to manage the condition. Under proper care, all patients are monitored regularly with blood testing and imaging.2 

Side effects of the listed dopaminergic drugs may include dizziness and nausea.2 In addition, the efficacy of the drugs may decrease with long-term use, so for both reasons, patients are started on low doses with dosage increased as needed. Most patients are able to tolerate these drugs, particularly cabergoline and quinagolide, but there are some people who are unable, and therefore, have to defer to other treatment options.13 Surgery and radiotherapy are the other two treatment options when a patient refuses or fails to respond well to pharmaceuticals.12, 2  Side effects of surgery may include damage to the normal tissue of the pituitary gland resulting in diabetes insipidus or the need for hormone replacement therapy. Other rare side effects of surgery may include post-operative bleeding, spinal fluid leak, stroke, or death.17  

During pregnancy, a woman’s pituitary gland increases in size and prolactin levels naturally rise significantly and progressively as it prepares the breasts for lactation.1, 5 Since the dopamine agonists used to treat prolactinoma and hyperprolactinemia suppress prolactin levels in the blood, special consideration must be given to female patients who become or wish to become pregnant while being treated for both conditions.2 Research shows that dopamine agonists, particularly bromocriptine and cabergoline, do not pose adverse effects to babies born from mothers who were treated with these drugs — even during the first trimester of pregnancy.16 “In women with microadenomas, pregnancy generally has little impact on their adenoma, delivery is normal and breast-feeding is allowed.” 15 However, as soon as pregnancy is suspected, women are taken off of the medication.

AYURVEDIC INTERPRETATION

An Ayurvedic interpretation of the development and treatment of prolactin-secreting adenoma of the pituitary gland can be inferred from the Ayurvedic understanding of anatomy, tissue development, and doshic qualities. Considering first the location of the pituitary gland being in the head, particularly the brain, what is the significance of the head? Chapter 17, verse 12 of the Charaka Samhita states, “the head is the substratum of elan vital and all the sense faculties. So it occupies the first place amongst the vital organs of the body.” 27 This is in alignment with the western, scientific understanding of the the brain as the control center of the body, including the pituitary gland, which is referred to as the master gland.3 

Being a part of the nervous system, Ayurveda considers the brain to be majja dhatu and part of the majjavaha srota. As stated in Principles of Ayurvedic Medicine by Dr. Marc Halpern, “the majja dhatu is commonly translated to mean the nervous system. However, the majja dhatu really relates to anything that fills an empty hollow space.” The pituitary gland is located in the base of the brain in a small, bony cavity (hollow space) of the skull called the sella turcica.3 Other relevant tissues involved in the condition of prolactinoma and majja dhatu include the optic nerve, which may be compressed by a macro-prolactinoma, and the neurotransmitter dopamine (also considered part of the nervous system and thus majja dhatu). 

The Ayurvedic explanation of dhatu formation agrees with the western, scientific understanding of the impact of pituitary gland dysfunction on the reproductive system. As the sixth dhatu, majja dhatu precedes the formation of shukra dhatu (ovaries and testes) and therefore, provides the posaka (unstable) majja to the shukra agni to transform posaka majja into shukra.28 If the formation of majja dhatu and posaka majja is of poor quality or there is faulty shukra agni, then the formation quality, quantity and function of shukra and artava dhatu will be disturbed. Dr. Sarita Shrestha notes that while classical Ayurvedic texts do not refer to hormones, hormones are considered to be dhatu agni.20 This makes sense given the role of hormones as transformational signals and metabolic directors to other sites of the body. Thus, prolactin could be considered shukra dhatu agni or artava dhatu agni. Milk ducts, the stanyavaha srota, originate in the artava dhatu. 

Classical Ayurvedic texts do not specifically discuss pituitary tumors or pituitary hormones; however, volume two of the Sushruta Samhita discusses the development and treatment of tumors (Gulma and Arbuda/Arvuda) and glandular swellings (Granthi).20, 21, 22, 23, 24, 25, 26 More specifically, gulma is understood to refer to hard, palpable masses in the abdomen (abdominal tumors), granthi refers to glandular swellings, benign tumors, or a tumor that is visible from the surface, and arbuda refers to a cancerous malignancy.29 Chapter 11, verses 11 – 12 of the Sushruta Samhita, volume two states, 

  • “the large vegetation of flesh which appears at any part of the body, becomes slightly painful, rounded, immovable and deep-seated, and has its root sunk considerably deep in the affected part, and which is due to the vitiation of the flesh and blood by the deranged and aggravated doshas is called an arbuda (tumor) by the learned physicians. The growth of an Arbuda is often found to be slow, and it seldom supperates [form or discharge pus]. The characteristic symptoms of an Arbuda which owes its origin to the deranged condition of the vayu, pitta, kapha, flesh or fat, are respectively identical with those, which mark the cases of Granthis, brought about by the same deranged principles of the body.” 24

Benign tumors, such as pituitary adenomas, are slow growing.30 Hence, one can infer from Sushruta that a prolactinoma is an arbuda or granthi. 

In considering the subtle body, it is likely that the ajna chakra (6th) may play a role in the pathology and/or treatment of prolactinoma and other pituitary adenomas. The ajna (“third eye”) chakra, “is the command station of the body and mind … contains the subtle qualities of ether … [and] affects the functions of the pituitary gland and hypothalamus.” 28 Increased flow through this chakra correlates to excess function of the pituitary and hypothalamus glands. 

SAMPRAPTI (PATHOLOGY) 

“From an Ayurvedic perspective, tumor formation is a condition of vata/kapha origin. Vata is responsible for the faulty division of cells and kapha for their growth. Hence, vata pushes kapha out of balance resulting in tumor formation. Benign tumors take on a predominantly kapha appearance,” writes Dr. Halpern. He continues, “Kapha plays the predominant role [in the development of granthi – benign tumors] as it enters the affected dhatus.” 29 Considering the potential role of vata, even in the development of a benign tumor, apana vayu accumulates and becomes aggravated in the rasa of the purishavaha srota and overflows to the rasa and rakta dhatus of the rasavaha and raktavaha srotas respectively. Prana vayu (of the head) and vyana vayu (“plays a role in the movement of the nerve energy”28) relocate to the majja dhatu of the majjavaha srota causing cell division (movement).   

Given that kapha (water and earth) is “the force of stability in the body,” is responsible for growth, and plays a lead role in the development of a benign tumor, kledaka kapha accumulates and becomes aggravated in the rasa of the annavaha srota, and overflows to the rasa and rakta dhatus of the rasavaha and raktavaha srotas respectively.28 Kapha then relocates to the majja dhatu of the majjavaha srota resulting in abnormal tissue growth (tumor) of lactotrophs of the anterior pituitary gland (majja). 

According to the Sushruta Samhita, Chapter 11, verse 2,  “the deranged and unusually aggravated vayu, etc. (pitta, kapha), by vitiating the flesh, blood and fat mixed with the kapha (of any part of the organism), give rise to the formation of round, knotty, elevated swellings which are called granthi (glandular inflammation).” In chapter 11, verses 3 – 5 “…the kaphaja granthi is slightly discolored and cold to the touch. It is characterised by a slight pain and excessive itching, and feels hard and compact as a stone. It is slow or tardy in its growth and exudes a secretion of thick white-coloured pus when it bursts.” 26 While Sushruta’s account of granthi formation does not fully explain the development of a pituitary tumor, it does suggest the kaphogenic development of a slow-growing tumor. 

As a result of the benign pituitary tumor and increase in prolactin secretion, symptoms (rupa) follow that result in further kapha and vata vitiation in other dhatus and srotas, including:  

  • ● Non-pregnancy/nursing Related Lactation: Tarpaka and avalambaka kapha relocates to the rasa dhatu of the stanyavaha srota. 
  • ● Irregular/Scanty Menses (Nashta Rakta): Excess shukra dhatu agni (hyperprolactinemia)  “burns up” or depletes shukra dhatu allowing apana vayu to flow into the artavavaha srota resulting in anovulation and a lack of menses. Vata (apana) may then relocate to asthi dhatu of the asthivaha srota resulting in decreased bone health and possible osteoporosis if left untreated.4 Vata may also relocate to the rasa dhatu of the artavavaha srota causing vaginal dryness, a possible side effect of anovulation and reproductive hormonal imbalance.4 
  • ● Headaches (Shiro Roga) and Vision Changes: Tarpaka kapha in the majja of the majjavaha srota (pituitary tumor) obstructs the majja (optical nerve and other cranial structures) resulting in vata pain and deranged alochaka pitta leading to vision changes. 

NIDANA (CAUSES)

Referring to kaphogenic diseases of the head, chapter 17, verses 24 – 25 of the Charaka Samhita states, “by sedentary habits, sleep during the daytime (when it is not desirable), excessive intake of heavy and unctuous food, the kapha of the head gets vitiated and causes head-disease.” 31 Considering the samprapti, the nidana of a benign tumor (arbuda/granthi) of the majja dhatu in the majjavaha srota includes:

Possible Vata Nidana

  • ● Vata-aggravating diet
  • ● Excess intake of cold, dry and light foods 
  • ● Irregular routines

Likely Kapha Nidana

  • ● Kapha-aggravating diet
  • ● Excess intake of heavy, unctuous, cold food
  • ● Sedentary habits
  • ● Sleep during the daytime

SADHYASYATA (PROGNOSIS)

An arbuda/granthi of the majja dhatu in the majjavaha srota (benign, prolactin-secreting tumor of the pituitary gland) is difficult to cure, not only from a western medical perspective, but also from an Ayurvedic perspective. Prolactinoma potentially involves the vitiation of two doshas in the sixth dhatu layer (majja).28 According to Sushruta, a benign pituitary tumor is incurable. The Sushruta Samhita, Chapter 11, verses 17 – 18, volume two states,

  • “… the following types of arbuda (tumors) should be likewise regarded as incurable, those which appear in the cavity of a srota channel or an artery, or any vulnerable point of the body and are characterised by any sort of secretion and also immovable, should be deemed incurable. … An arbuda of whatsoever type, never suppurates owing to the exuberance of the deranged kapha and fat as well as in consequence of the immobility, condensation and compactness of the deranged doshas.”

As stated earlier, the pituitary gland resides in the cavity of the sella turcica.3 Indeed, some patients require lifelong, western pharmaceutical treatment in order to manage their prolactinoma.32

CHIKITSA (TREATMENT)

Despite the prognosis of ‘difficult to treat or cure’, and even potentially ‘incurable’, Ayurveda provides possibilities for cure, including approaches to tumor reduction and the management of prolactinemia. Sushruta (volume two, chapter 18, verses 28 – 40) presents an array of possibilities for the treatment of arbuda; however, all of the treatments presented call for external applications directly to the tumor.26 This approach is not applicable in the case of pituitary tumors. 

As with any Ayurvedic treatment, the first step is to clear ama (toxicity) and regulate agni (digestive fire). If the patient is strong enough, the patient should undergo panchakarma (langhana chikitsa) to clear ama and alleviate excess kapha and vata doshas from the body. Following purvakarma, an emphasis of vamana, niruha and anuvasana basti, and nasya therapies should be considered. Nasya is likely to be a very effective therapy in order to remove vitiated doshas from the head. If a patient is not strong enough, a palliative approach to clear ama and regulate agni should be taken (shamana chikitsa).28 

Following shodhana chikitsa (langhana or shamana chikitsa) and samsarjana krama, a variety of kapha-pacifying dietary, lifestyle, herbal and body therapies should be considered in the Ayurvedic treatment of prolactinoma. Care must also be taken to prevent vata vitiation. 

In addition to directing treatment to emphasize tumor reduction (kapha pacification), the management of prolactin levels with dopaminergic herbs should also be a part of treatment if a patient is not managing prolactin with an integrative approach that includes western, dopaminergic drugs. 

Diet, Lifestyle and Sensory Therapies in the Treatment of Prolactinoma  

In order to reverse the nidana, a kapha-pacifying diet should be followed and include an emphasis on bitter and pungent tastes. A lifestyle including stable routines (to manage vata), no oversleeping, and exercise (including kapha-pacifying yoga asana) should be followed. Appropriate body therapies in addition to nasya may include medicated shiro basti and shirodhara using light oils, such as safflower. Abhyanga, along with anuvasana basti, will also be important for managing vata.

Aroma therapies may include the use of frankincense, which has been shown (boswellia sacra) to have anti-tumor properties.34 Other kapha-pacifying essential oils to consider include, myrrh, basil, wintergreen and cinnamon. Chromotherapies may include exposure to the kapha-vata reducing colors of yellow and green as well as the balancing effects of the color gold.28  

Given Ayurveda’s comprehensive approach to treatment that addresses mind, body and spirit, other subtle therapies to be considered include daily meditation, visualization of a healthy pituitary gland and tumor shrinkage, alternate-nostril breathing for balancing nadi flow, and the chanting of all seven bija mantras (if the patient’s ojas is strong). The chanting of kshum (6th chakra bija mantra) to balance the ajna chakra may also be helpful due to the chakra’s connection to the hypothalamus and pituitary gland.28

Therapeutic Herbs in the Treatment of Prolactinoma and Hyperprolactinemia

Dr. David Frawley explains in Ayurvedic Healing that the herbal treatment for cancer should include all of the following categories of action: alteratives, circulatory stimulants, immune strengthening tonics, expectorants, and strong bitter or pungent herbs with fat-reducing and toxin-destroying properties.33 While prolactinoma is not regarded as cancerous,4 an herbal, anti-cancer approach should prove beneficial in efforts to reduce tumor size or growth. All of the herbal categories Frawley mentions have anti-tumor properties.36 Dr. A. A. Mundewadi is Chief Ayurvedic Physician at Mundewadi Ayurvedic Clinic based at Thane, Maharashtra, India. He states, “pituitary gland tumors (which secrete excess prolactin) may be treated with Kanchnaar Guggulu, Panch Tikta Ghruta Guggulu, Guduchi (Tinospora cordifolia), Amalaki (Emblica officinalis), Mogra (Jasminum sambac) and Musta (Cyperus rotundus).” 38 Given that symptoms of prolactinoma, such as amenorrhea, galactorrhea, and impotence are the result of the secreting pituitary adenoma, the focus of herbal treatment for prolactinoma should be placed on tumor reduction and managing prolactin levels. This is likely to be best achieved with micro-adenoms. Macro-adenoms may require western medical treatment depending on the severity of symptoms, such as headaches and vision changes from nerve compression. 

In addition to a variety of kapha-pacifying, reducing herbs, the following herbs should be especially considered for tumor reduction:35, 36 

Guggulu
  • Rasa: Bitter, Pungent, Astringent
  • Virya: Warming
  • Vipaka: Pungent (Reducing)
  • Guna: Light, Penetrating, Dry
  • Doshic:         VPK- (P+ in excess)
  • Dhatus:         All tissues
  • Srotas: Circulatory, Digestive, Nervous, Respiratory
  • Actions:         Anti-inflammatory, antiplatelet, anti-cholesterolaemic, astringent, antiseptic, immune 
  •                         stimulant, emmenagogue, 
  • Uses: Clears ama, Penetrates deeply into the tissues, menstrual irregularities, tumors 
  • Contraindication: Pregnancy, Breast-feeding

Kanchanar

  • Rasa: Bitter, Astringent
  • Virya: Cold
  • Vipaka: Pungent
  • Guna: Dry, Light
  • Doshic: K, P -, V+
  • Dhatus: Blood, Muscle, Fat, Bone, Reproductive
  • Srotas: Female Reproductive
  • Actions:         Lymphatic, alterative, astringent, haemostatic, vulnerary, uterine tonic, antispasmodic, emetic, expectorant, anti-inflammatory 
  • Uses:         Tumors and Glandular Swellings(All forms of swellings, lumps, growths), Fibroids, Endometriosis, Cysts 
  • Contraindications: Pregnancy, Constipation

Kanchanar Guggulu Formula

  • Rasa: Bitter, Astringent, Sweet, Pungent
  • Virya: Heating
  • Vipaka: Pungent
  • Guna: Dry, Light
  • Doshic: K-, VPK=
  • Dhatus: Plasma, Blood, Fat, Bone, Reproductive
  • Srotas: Circulatory, lymphatic, eliminator
  • Actions:         Anti-inflammatory, lymphatic, antitumour, antiplatelet, diuretic, reduces cholesterol, alterative, decongestant 
  • Uses: Destroys ama, tumors, growths and cancers, 
  • Formula Includes: Kanchanar, Triphala (amalaki, haritaki, bibhitaki), Trikatu (black pepper, long pepper, ginger), Varuna, Cardamom, Guggulu, Cinnamon

“Growths: Kañcanara guggulu is a specific for clearing all growths and fluid-based accumulations in the body. It specifically reduces swellings and lumps(soft/hard/palpable/fixed/moveable)by drying the excess kapha. It is a favoured formula used in cancer caused by excess kapha. Also consider it in anal fistulas,abscesses and chronic skin lesions.”  – Sebastian Pole 35

The following herbs should be especially considered for inhibiting prolactin:35, 37, 39, 40, 41 

Vitex (Chasteberry) (Agnus Castus)

  • Rasa: Bitter, Pungent, Astringent
  • Virya: Cooling and Warming
  • Guna: Dry
  • Actions:         Emmenogogue, Vulnerary, Dopaminergic, Progesteronic, 
  • Uses:         PMS, Menstrual Irregularities, Menopause, Ovarian Cysts, Breast Lumps, Prolactinoma.
  • Contraindications: Pregnancy, Breast-feeding
  • Note: Minimal chronic known toxicity.

Kappikacchu (Cowhage) (Mucuna pruriens–Semen)  

  • Rasa:         Sweet, Bitter
  • Virya:         Hot
  • Vipaka: Sweet
  • Guna: Unctuous, Heavy
  • Dosha: VP-, K+
  • Dhatu: All tissues, especially nerve and reproductive
  • Srota: Nervous, reproductive, digestive
  • Actions:         Aphrodisiac, Antispasmodic, Carminative, Dopaminergic
  • Uses:         Parkinson’s Disease, Low Libido, Impotence, Spermatorrhea

While kappikacchu is dopaminergic and research show that it may have an inhibitory effect on prolactin, it is kapha increasing, so may not be ideal for prolactinoma. It may be better used for other hyperprolactinemia conditions.

CONCLUSION

Ayurveda, whether used as a complementary approach to the allopathic treatment of prolactinoma or as an alternative, offers the possibility of complete healing. This is especially true for those with micro-prolactinomas and moderate prolactin elevation. As a complementary approach, Ayurveda can support healing by reversing the nidana and alleviating vitiated kapha and vata while a patient stabilizes his or her prolactin levels with prescription drugs. As an alternative approach, Ayurveda offers another option to those who have adverse reactions to pharmaceutical medication, lack insurance, or simply refuse to use allopathic treatment. By addressing diet, sleep, daily routines, mediation, exercise, and other lifestyle choices, Ayurveda leaves no aspect of living unaccounted for. Everything we do, consume, think, speak, or say has an influence on our health and can either encourage disease or promote healing. The comprehensive, healing protocols of Ayurveda offer sufferers of prolactinoma a proactive role in their healing that goes beyond taking daily medication, getting yearly MRIs and hoping for the best. 

Symptoms of prolactinoma and hyperprolactinemia — nashta rakta (amenorrhea) or oligomenorrhea, inappropriate lactation (galactorrhea), shiro roga (headaches), vision changes, infertility, and/or low libido — can result from various other causes. If these symptoms appear, especially together, a medical evaluation is required to confirm (or rule out) hyperprolactinemia and the presence and size of a secreting-pituitary adenoma. Due to the consequences of abnormally high prolactin levels (infertility, increased risk of osteoporosis, low libido, possible tumor growth), an integrative approach to care, combining allopathic and Ayurvedic medicine, should be taken in order to monitor prolactin levels and tumor size. Herbal management of prolactin may be tried for a period of time before a patient is put on cabergoline or another dopamine agonist while using Ayurvedic approaches to clear ama, restore agni and alleviate vitiated doshas to reduce tumor size.

Many questions remain to fully understand the cause and treatment of prolactinoma, including: 

  • ● How may estrogen play a role in the development of prolactinoma?
  • ● What is the comparative analysis of those diagnosed with prolactinoma (noting tumor size) and their exposure to xenoestrogen?
  • ● What is the comparative analysis of those diagnosed with prolactinoma (noting tumor size) and their prakruti and vikruti at the time of diagnosis?
  • ● What are the effects of vitex on estrogen, progesterone and prolactin at varying dosages?
  • ● What are the effects of kanchanar, guggulu, and/or kanchanar guggulu on tumor size?

According to the Neuroendocrine Clinical Center at the Massachusetts General Hospital, “Autopsy studies indicate that 25 percent of the U.S. population have small pituitary tumors. Forty percent of these pituitary tumors produce prolactin, but most are not considered clinically significant. Clinically significant pituitary tumors affect the health of approximately 14 out of 100,000 people.” 42 While the number of those affected with prolactinoma is small, each individual life is significant and optimal health is a birthright for all, therefore, further research and contemplation is needed from both an allopathic and Ayurvedic perspective to more fully understand and better treat prolactinoma.

APPENDICES

APPENDIX I – Endnotes
APPENDIX II – Samprapti Chart
APPENDIX III – Clinical Abstracts
 
APPENDIX I – ENDNOTES
 
1 Pituitary Network Association, PNA Staff. 
  
2 Medline Plus, Nancy J. Rennert, MD, Updated December 11, 2011. 
3 American Brain Tumors Association, ABTA Staff. Pituitary Tumors Brochure PDF. 
http://www.abta.org/secure/pituitary-tumors-brochure.pdf
 
4 National Endocrine and Metabolic Diseases Information Service, Staff, Updated April 6, 2012. http://endocrine.niddk.nih.gov/pubs/prolact/prolact.aspx#common 
 
5 Britannica, Robert D. Utiger, Prolactin and Prolactin Deficiency and Excess, http:// www.britannica.com/EBchecked/topic/478570/prolactin 
 
6 Fraioli F, Paolucci D, Dondero F, Spera G, Isidori A. “Prolactin secreting adenoma in man and the role of prolactin in spermatogenesis.” Journal of Endocrinological Investigation. 1980 Apr- Jun;3(2):155-61. http://www.ncbi.nlm.nih.gov/pubmed/7391522  
 
7  Kipak K. Sarkar, “Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals,”  Pituitary Today: Molecular, Physiological and Clinical Aspects. Front Horm Res. Basel, Karger, 2006, vol 35, pp 32-49 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882189/ 
 
8  Tatiana Goloubkova, Maria Flávia M. Ribeiro, Luciene P. Rodrigues, Ana L. Cecconello and Poli Mara Spritzer, “Effects of xenoestrogen bisphenol A on uterine and pituitary weight, serum prolactin levels and immunoreactive prolactin cells in ovariectomized Wistar rats.”  Archives of Toxicology, Vol. 74, Number 2 (2000), 92-98. http://www.springerlink.com/content/01mqcap3wwbw1umk/ 
 
9  American Society for Reproductive Medicine, Hyperprolactinemia Fact Sheet, Staff. http://www.asrm.org/uploadedFiles/ASRM_Content/Resources/Patient_Resources/Fact_Sheets_and_Info_Booklets/Prolactin_Excess.pdf 
 
10  Nomikos P, Buchfelder M, Fahlbusch R. “Current management of prolactinomas.” Journal of Neuro-Oncology, 2001 Sep;54(2):139-50. http://www.ncbi.nlm.nih.gov/pubmed/11761431
 
11 M. J. Levy, M. S. Matharu, K. Meeran, M. Powell, and P. J. Goadsby. “The clinical characteristics of headache in patients with pituitary tumours.” Brain: A Journal of Neurology.  (August 2005) 128 (8):1921-1930. http://brain.oxfordjournals.org/content/128/8/1921.full 
 
12 Verhelst J, Abs R. “Hyperprolactinemia: pathophysiology and management.” Treatments in Endocrinology. 2003;2(1):23-32. http://www.ncbi.nlm.nih.gov/pubmed/15871552
 
13 Ciccarelli E, Camanni F. “Diagnosis and drug therapy of prolactinoma.” Drugs. 1996 Jun;51(6):954-65. http://www.ncbi.nlm.nih.gov/pubmed/8736617
 
14 Syed Ali Imran, Ehud Ur, and David B. Clarke. “Managing Prolactin-Secreting Adenomas During Pregnancy.” Canadian Family Physician. April 2007 vol. 53 no. 4 653-658. http://www.cfp.ca/content/53/4/653.full 
15 Christin-Maître S, Delemer B, Touraine P, Young J. “Prolactinoma and estrogens: pregnancy, contraception and hormonal replacement therapy.”  Annales d’Endocrinologie (Paris). 2007 Jun;68(2-3):106-12. Epub 2007 May 30. http://www.ncbi.nlm.nih.gov/pubmed/17540335 
 
16 The Pituitary Society, Staff. Fertility Issues. http://www.pituitarysociety.org/public/specific/prolactinoma/fertility.aspx  
 
17 Massachusetts General Hospital Neuroendocrine Clinical Center. Frequently Asked Questions About Transsphenoidal Surgery For Pituitary Adenomas: A Patient Guide.  http://pituitary.mgh.harvard.edu/TranssphenoidalSurgery.htm 
 
18 University of Michigan Health System: Prolactinoma. Staff. http://www.med.umich.edu/1libr/aha/umneuro_prolactinoma.htm 
 
19 Pituitary Network Association, By Peter N. Riskind, M.D., Ph.D. Headaches and Pituitary Tumors. https://www.pituitary.org/library/library_detail.aspx?page_id=1284  
 
20 Dr. Sarita Shrestha: Women’s Health. http://www.saritashrestha.org/women.html 
 
21 Sushruta. Sushruta Samhita Volume II (Varanasi: Chowkhamba Sanskrit Series Office, 2nd Edition. 2000) Chapter 9, Verses 28 – 29
 
22 Sushruta. Sushruta Samhita Volume II (Varanasi: Chowkhamba Sanskrit Series Office, 2nd Edition. 2000) Chapter 9, Verses 30 – 33
 
23 Sushruta. Sushruta Samhita Volume II (Varanasi: Chowkhamba Sanskrit Series Office, 2nd Edition. 2000) Chapter 11, Verses 2 – 5
 
24 Sushruta. Sushruta Samhita Volume II (Varanasi: Chowkhamba Sanskrit Series Office, 2nd Edition. 2000) Chapter 11, Verses 11 – 12
 
25 Sushruta. Sushruta Samhita Volume II (Varanasi: Chowkhamba Sanskrit Series Office, 2nd Edition. 2000) Chapter 11, Verses 17 – 18
 
26 Sushruta. Sushruta Samhita Volume II (Varanasi: Chowkhamba Sanskrit Studies Office, 2nd Edition. 2000) Chapter 18, Verses 28 – 40
 
27 Charaka. Charaka Samhita Volume I (Varanasi: Chowkhamba Sanskrit Studies Office.) Chapter 17, Verse 12
 
28 Marc Halpern, DC, CAS, PKS. Principles of Ayurvedic Medicine, 10th Ed. Pg. 81, 94-95, 144, 219, 229, 334
 
29 Marc Halpern, DC, CAS, PKS. “Managing Cancer, Part II: Ayurvedic Knowledge and Holistic Therapy” Textbook of Clinical Ayurvedic Medicine Part II. 2003. Pg. 1, 4
 
30 Benjamin Frank Miller. Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health (WB Saunders Company. 1997, Sixth Edition). Pg. 1667
 
31 Charaka. Charaka Samhita Volume I (Varanasi: Chowkhamba Sanskrit Studies Office.) Chapter 17, Verse 24 – 25
 
32 Colao A. “Pituitary tumours: the prolactinoma.” Best Practice and Research: Clinical Endocrinology and Metabolism. 2009 Oct;23(5):575-96. http://www.ncbi.nlm.nih.gov/pubmed/19945024 
 
33 David Frawley. Ayurvedic Healing: A Comprehensive Guide, 2nd edition. (Twin Lakes: Lotus Press. 2000) Pg. 286 – 287
 
34 Mahmoud M Suhail, Weijuan Wu, Amy Cao, Fadee G Mondalek, Kar-Ming Fung, Pin-Tsen Shih, Yu-Ting Fang, Cole Woolley, Gary Young, and Hsueh-Kung Lin. “Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells” BioMedCentral Complementary and Alternative Medicine. 2011; 11: 129. Published online 2011 December 15. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258268/ 
 
35 Sebastian Pole. Ayurvedic Medicine: The Principles of Traditional Practice (London/Philadelphia: Churchill, Livingstone, Elsevier, 2006) Pg. 191 – 192, 204 – 205, 306 – 307
 
36 Dr. David Frawley and Dr. Vasant Lad. The Yoga of Herbs: An Ayurvedic Guide to Herbal Medicine, 2nd Edition. (Twin Lakes: Lotus Press 1986, 2001) Pg. 33, 39, 49, 56, 63
 
37 Sliutz G, Speiser P, Schultz AM, Spona J, Zeillinger R. “Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.” Hormone and Metabolic Research (University of Vienna, Austria). 1993 May;25(5):253-5. http://www.ncbi.nlm.nih.gov/pubmed?term=vitex%20agnus%20pituitary%20gland 
 
38 Dr. Abdulmubeen Mundewadi. Female Infertility — Ayurvedic Herbal Treatment.  http://ezinearticles.com/?Female-Infertility—Ayurvedic-Herbal-Treatment&id=1486596 
 
39 Leblanc H, Yen SS. “The effect of L-dopa and chlorpromazine on prolactin and growth hormone secretion in normal women.” American Journal of Obstetrics and Gynecology. 1976 Sep 15; 126(2): 162-4. http://www.ncbi.nlm.nih.gov/pubmed/961756 
 
40 Peter Holmes. The Energetics of Western Herbs: Treatment Strategies Integrating Western and Oriental Medicine, Volume Two, 3rd Edition. (Boulder: Snow Lotus Press, 1997) Pg. 597 – 599
 
41 Michael Tierra. Planetary Herbology. (Twin Lakes: Lotus Press, 1988) Pg. 282
 
42 Massachusetts General Hospital Neuroendocrine Clinical Center.  Prolactinoma Resources.  http://pituitary.mgh.harvard.edu/prolacti.htm
 
APPENDIX II – SAMPRAPTI CHART
RUPASAMPRAPTIDOSHASUBDOSHADHATUDHATU Incr/DecrSROTAHERBS
PPM Sluggish Digestion & NauseaA/AKaphaKledakaRasaIncreaseAnnavahaDipanas
MT Systemic SwellingOKaphaN/SRasaIncreaseRasavahaDiuretics Diaphoretic
MT Lethargy & PaleOKaphaN/SRaktaIncreaseRaktavahaCirculatory Stimulans
Growth of anterior pituitary adenomaRMDKaphaTarpakaMajjaIncreaseMajjavahaAnti-tumor
Non-pregnancy related breast lactationRMDKapha

Tarpaka

Avalambaka

RasaIncrease

Majjavaha

Stanyavaha

Anti-galactogues
Male breast tissue growthRMDKaphaAvalambaka

Medas

Rakta

Increase

Increase

Medovaha

Raktavaha

Cholegogu, Lekhanas, Alteratives
PPM Constipation & GasA/AVataApanaRasaDecreasePurishavahaLaxatives Demulcents Carminative
MT Systemic DrynessOVataVyanaRasaDecreaseRasavahaDemulcents
MT Feeling cold & fatigueOVataVyanaRaktaDecreaseRaktavahaCirculatory Stimulants
Irregular and/or Absence of Menses, Low libidoRMDVataApana

Shukra

Artava

DecreaseShukravaha (Men) ArtavahaEmmenogogues Reproductive Tonics, Demulcents
Vaginal DrynessRMDVataVyanaShukraDecreaseArtavahaDemulcents
MT Bone weakness (risk for osteoperosisRMDVataApanaAsthiDecreaseAsthivahaBone Tonics
 
APPENDIX III – CLINICAL ABSTRACTS 

6 Fraioli F, Paolucci D, Dondero F, Spera G, Isidori A. “Prolactin secreting adenoma in man and the role of prolactin in spermatogenesis.” Journal of Endocrinological Investigation. 1980 Apr- Jun;3(2):155-61. http://www.ncbi.nlm.nih.gov/pubmed/7391522

Abstract
The case of a 23-year-old man with a pituitary prolactin secreting adenoma is described. With the exception of prolactin all endocrinological parameters were normal. This finding provided an ideal opportunity to assess the role of prolactin on spermatogenesis. Sperm analysis and light microscopy examination of testicular biopsy showed normal spermatogenesis. Electron microscopic studies of the testicular specimen revealed the presence of undivided spermatids, containing two or more nuclei, partially embedded in a developing common acrosome. Morphological studies demonstrated a constant “paired” situation. In most instances two sperms were contained in a single membrane; no single sperm was detected. Following treatment with 5 mg/day bromocriptine prolactin levels decreased and this peculiar abnormality disappeared. In fact, after 2 months of treatment the sperm abnormalities were markedly reduced, whereas no change was found after a period of 120 days. Since this was the only alteration found in the patient with high prolactin levels, a correlation was sought between prolactin levels and cell division. Considering the similarities between prolactin and growth hormone, it might be possible to attribute to prolactin a growth hormone role in the germinal epithelium. This action could be either direct or indirect via an intermediate growth factor.
 
7  Kipak K. Sarkar, “Genesis of Prolactinomas: Studies Using Estrogen-Treated Animals,”  Pituitary Today: Molecular, Physiological and Clinical Aspects. Front Horm Res. Basel, Karger, 2006, vol 35, pp 32-49 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882189/
 
Abstract
Prolactin-secreting adenomas (prolactinomas) are the most prevalent form of pituitary tumors in humans. Our knowledge of the formation of these tumors is limited. Experimental work in animal has uncovered that estradiol exposure leads to prolactinoma formation via orchestrated events involving dopamine D2 receptors, transforming growth factor-β (TGF-β) isoforms and their receptors, as well as factors secondary to TGF-β action. Additionally, these studies determined that TGF-β and b-FGF interact to facilitate the communication between lactotropes and folliculo-stellate cells that is necessary for the mitogenic action of estradiol. The downstream signaling that governs lactotropic cell proliferation involves activation of the MAP kinase p44/42-dependent pathway.
Pituitary tumors are primarily adenomas; they account for approximately 10–15% of intracranial tumors. They cause significant morbidity due to local invasion, hypopituitarism or hormone hypersecretion [1, 2]. Pituitary tumors are classified as either functioning and secreting excessive amounts of active hormones, or as endocrinologically inactive and secreting no hormones or inactive hormones. Pituitary tumors are also classified by virtue of their size into the arbitrary division of those less than 1 cm as microadenomas and those more than 1 cm as macroadenomas. Pituitary tumors secreting excess prolactin are characterized as prolactinomas. Prolactinomas are the most frequently occurring neoplasm in the human pituitary [3, 4]. In the general population, 1:2,800 men and 1:1,050 women are considered to have prolactinomas [5]. In human subjects, prolactinomas occur as both macroadenomas and microadenomas. In addition, mixed growth hormone and prolactin-secreting adenomas are documented to exist in a substantial number of acromegaly patients.  Hyperprolactinoma is a condition in which plasma prolactin (PRL) levels are elevated above normal levels. Hyperprolactinemia, with elevation of serum prolactin of more than 200 ng/ml, is characteristically associated with prolactinomas [6]. Hyperprolactinemia causes reproductive dysfunction such as amenorrhea, galactorrhea, and infertility in women [7]. Amenorrhea and galactorrhea may occur alone or together [8]. Up to 25% of patients with secondary amenorrhea have been diagnosed with hyperprolactinemia. Many of these patients showed micro-prolactin adenomas or macro-prolactin adenomas in the pituitary. Although treatments that alter central dopaminergic neuronal functions cause an elevated serum PRL level, in most cases hyperprolactinemia is due to a pituitary tumor. In women, prolactinomas are mainly microadenomas. These microadenomas are rarely associated with hypopituitarism or central nervous system dysfunction. Idiopathic hyperprolactinemia, without demonstrable pituitary or hypothalamic disease, has also been identified. In men, prolactinomas are mainly macroadenomas [9]. These patients often exhibit gynecomastia, impotence, decreased libido, and reduced reproductive hormone levels [10].
The genesis of prolactinoma in lactotropes of the pituitary gland or other pituitary tumors remains for the most part a subject of speculation and debate because cells involved in the formation of adenoma may be derived from monoclonal or polyclonal expansion and may have phenotypes that change during tumor development and therefore are very hard to discern. However, information of genetic modifications that increase the risk factors for lactotropic tumors has begun to decipher from animal studies in which prolactinoma is induced by estrogen.
 
8  Tatiana Goloubkova, Maria Flávia M. Ribeiro, Luciene P. Rodrigues, Ana L. Cecconello and Poli Mara Spritzer, “Effects of xenoestrogen bisphenol A on uterine and pituitary weight, serum prolactin levels and immunoreactive prolactin cells in ovariectomized Wistar rats.”  Archives of Toxicology, Vol. 74, Number 2 (2000), 92-98. http://www.springerlink.com/content/01mqcap3wwbw1umk/ 
 
Abstract
Considerable attention has currently been focused on bisphenol A (BPA), an environmental endocrine disrupting chemical that has oestrogenic activity. In vitro and in vivo short-term assays have shown that BPA is weakly estrogenic. In addition, the issue of species- and strain-differences in susceptibility to BPA was raised. The treatment of ovariectomized (OVX) Wistar rats with BPA at doses of 11–250 mg/kg per day, s.c., for 7 days, resulted in significant dose-dependent re-growth of uterus in uterotrophic assay. Additionally, the stimulation of anterior pituitary gland growth and induction of hyperprolactinaemia, as determined by wet organ weight and radioimmunoassay (RIA), respectively, were also dose-dependent (at 128 and 250 mg/kg per day, P < 0.05). Prolactin immunostaining of anterior pituitary glands revealed that BPA at a dose of 250 mg/kg per day increased the number of prolactin-immunopositive cells by 63% compared to OVX rats. These results demonstrate that the reproductive tract and neuroendocrine axis of Wistar rats are able to respond to BPA. Furthermore, the pituitary gland hypertrophy and hyperprolactinaemia can be mediated, at least partly, by increase in number of prolactin-immunoreactive cells. The long-term consequences of this proliferation are yet unknown but neoplasm formation is an obvious possibility.
 
10  Nomikos P, Buchfelder M, Fahlbusch R. “Current management of prolactinomas.” Journal of Neuro-Oncology, 2001 Sep;54(2):139-50. http://www.ncbi.nlm.nih.gov/pubmed/11761431
 
Abstract
Prolactinomas constitute the largest group of pituitary adenomas in autopsy series. However, their relative incidence in recent surgical series is much less impressive since medical treatment with dopamine agonists is routinely employed, which in many cases leads to tumor shrinkage and normalization of prolactin levels. The clinical symptoms of hyperprolactinemia are menstrual dysfunction and galactorrhea in women and loss of libido and potency in men. Prolactinomas may present also as space occupying sellar mass lesions impinging on the adjacent structures like the pituitary gland, cavernous sinus and optic nerves. The standard primary treatment is medical by dopamine agonists. Prolactinomas are the prototype of tumors, the growth of which can be reliably and safely inhibited by specific drugs other than cytostatic chemotherapy. These unfortunately have side effects, like orthostatic hypotension, nausea and vomiting. The effects induced by dopamine agonists are suppressive but not tumoricidal. Thus, the therapeutic effect is only maintained as long as the drug is administered. Consequently. in most cases, treatment has to be continued life-long with a few exceptions, in whom normoprolactinemia persists even after discontinuation of dopamine agonists. Main indications of surgery in prolactinomas are intolerance of the medication, and tumors not responding to dopamine agonists. Occasionally, these may ultimately require radiation therapy. Remission rates in large series of surgically treated prolactinomas vary between 54% and 86%. In our consecutive series of 540 surgically treated prolactinomas, the normalization rate after transsphenoidal surgery basically depended on the preoperative prolactin levels, tumor size and extension. The remission rate of 82% in microprolactinomas with initial prolactin levels <200 ng/ml would even in small adenomas make one consider surgical treatment as an interesting alternative to long-term medical treatment.
 
11 M. J. Levy, M. S. Matharu, K. Meeran, M. Powell, and P. J. Goadsby. “The clinical characteristics of headache in patients with pituitary tumours.” Brain: A Journal of Neurology.  (August 2005) 128 (8):1921-1930. http://brain.oxfordjournals.org/content/128/8/1921.full 
 
Summary
The clinical characteristics of 84 patients with pituitary tumour who had troublesome headache were investigated. The patients presented with chronic (46%) and episodic (30%) migraine, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT; 5%), cluster headache (4%), hemicrania continua (1%) and primary stabbing headache (27%). It was not possible to classify the headache according to International Headache Society diagnostic criteria in six cases (7%). Cavernous sinus invasion was present in the minority of presentations (21%), but was present in two of three patients with cluster headache. SUNCT-like headache was only seen in patients with acromegaly and prolactinoma. Hypophysectomy improved headache in 49% and exacerbated headache in 15% of cases. Somatostatin analogues improved acromegaly-associated headache in 64% of cases, although rebound headache was described in three patients. Dopamine agonists improved headache in 25% and exacerbated headache in 21% of cases. In certain cases, severe exacerbations in headache were observed with dopamine agonists. Headache appears to be a significant problem in pituitary disease and is associated with a range of headache phenotypes. The presenting phenotype is likely to be governed by a combination of factors, including tumour activity, relationship to the cavernous sinus and patient predisposition to headache. A proposed modification of the current classification of pituitary-associated headache is given.
 
12 Verhelst J, Abs R. “Hyperprolactinemia: pathophysiology and management.” Treatments in Endocrinology. 2003;2(1):23-32. http://www.ncbi.nlm.nih.gov/pubmed/15871552
 
Abstract
Hyperprolactinemia is commonly found in both female and male patients with abnormal sexual and/or reproductive function or with galactorrhea. If serum prolactin levels are above 200 microg/L, a prolactin-secreting pituitary adenoma (prolactinoma) is the underlying cause, but if levels are lower, differential diagnoses include the intake of various drugs, compression of the pituitary stalk by other pathology, hypothyroidism, renal failure, cirrhosis, chest wall lesions, or idiopathic hyperprolactinemia. When a pituitary tumor is present, patients often have pressure symptoms in addition to endocrine dysfunction, such as headaches, visual field defects, or cranial nerve deficits. The large majority of patients with prolactinomas, both micro- and macroprolactinomas, can be successfully treated with dopaminergic drugs as first-line treatment, with normalization of prolactin secretion and gonadal function, and with significant tumor shrinkage in a high percentage of cases. Surgical resection of the prolactinoma is the option for patients who may refuse or do not respond to long-term pharmacological therapy. Radiotherapy and/or estrogens are also reasonable choices if surgery fails. In patients with asymptomatic microprolactinoma no treatment needs to be given and a regular follow-up with serial prolactin measurements and pituitary imaging should be organized. Currently, the most commonly used dopamine agonists are bromocriptine, pergolide, quinagolide and cabergoline. When comparing the plasma half-life, efficacy and tolerability of these drugs, cabergoline seems to have the most favorable profile, followed by quinagolide. Ifprolactin levels are well controlled with dopamine agonist therapy, gradual tapering of the dose to the lowest effective amount is recommended, and in a number of cases medication can be stopped after several years. Evidence to date suggests that cabergoline and quinagolide appear to have a good safety profile for women who wish to conceive, but hard evidence proving that dopamine agonists do not provoke congenital malformations when taken during early pregnancy is currently only available for bromocriptine. Once pregnant, dopamine agonist therapy should be immediately stopped, unless growth of a macroprolactinoma is likely or pressure symptoms occur. At our institution patients with symptomatic prolactinomas, both micro- and macroadenomas, are treated with cabergoline as the first-line aproach. In the small group of patients who do not respond to this treatment, or who refuse long-term therapy, surgery is offered. Radiotherapy is given if both pharmacologic therapy and surgery fail.
 
13 Ciccarelli E, Camanni F. “Diagnosis and drug therapy of prolactinoma.” Drugs. 1996 Jun;51(6):954-65. http://www.ncbi.nlm.nih.gov/pubmed/8736617
 
Abstract
A prolactin-secreting pituitary tumour is the most frequent cause of hyperprolactinaemia that commonly occurs in clinical practice. Prolactinomas occur more frequently in women than in men and may differ in size, invasive growth and secretory activity. At presentation, macroadenomas are more frequently diagnosed in men. Specific immunohistochemical stains are necessary to prove the presence of prolactin in the tumour cells. The main investigations in the diagnosis of a prolactin-secreting adenoma are hormonal and radiological. As prolactin is a pulsatile hormone, it is a general rule to obtain several blood samples by taking a single sample on 3 separate days or 3 sequential samples (every 30 minutes) in restful conditions. Prolactin levels of 100 to 200 micrograms/L are commonly considered diagnostic for the presence of a prolactinoma; however, prolactinoma cannot be excluded in the presence of lower levels, and prolactin levels > 100 micrograms/L are present in some patients with idiopathic hyperprolactinaemia. Several dynamic function tests have been proposed to differentiate idiopathic from tumorous hyperprolactinaemia. Although they could be used for group discrimination, these tests cannot be used for individual patients. To differentiate between a prolactinoma and a pseudoprolactinoma, thyrotrophin response to a dopamine receptor antagonist may be used, as only prolactinomas may have an increased response. A short course of dopaminergic drugs may also be of some help, as in macroprolactinomas only a shrinkage may be observed. After hyperprolactinaemia is confirmed, imaging with computerised tomography (CT) and magnetic resonance imaging (MRI) are necessary to define the presence of a lesion compatible with a pituitary tumour. There is now a general agreement that medical therapy is of first choice in patients with prolactinomas. Bromocriptine, the most common drug used in this condition, is a semisynthetic ergot alkaloid that directly stimulates specific pituitary cell membrane dopamine D2 receptors and inhibits prolactin synthesis and secretion. In most patients, a reduction or normalisation of prolactin levels is usually observed, together with the disappearance or improvement of clinical symptoms. The sensitivity to bromocriptine is variable and patients may need different dose of the drug. Bromocriptine is also able to shrink the tumour in most patients; however, a few reports of disease progression during therapy have been described. The need for close follow-up, including prolactin levels and CT or MRI studies, is therefore emphasised. Bromocriptine is conventionally given in 2 or 3 daily doses; however, a single evening dose has been shown to be equally effective. Bromocriptine is usually well tolerated by the majority of patients; some adverse effects (nausea, vomiting, postural hypotension) may be initially present, but they usually wear off in time. To prevent such adverse effects it is advisable to start treatment with a low dose during the evening meal and gradually increase the dose over days or weeks. A few patients are unable to tolerate oral bromocriptine, so different formulations of bromocriptine or alternative dopamine agonist drugs (lisuride, terguride, metergoline, dihydroergocryptine, quinagolide, cabergoline, pergolide) have been proposed. Of particular clinical relevance because of their good tolerability and sustained activity are cabergoline and quinagolide. Particular attention should be paid to pregnancy in prolactinoma patients, as tumour enlargement has been reported. As the risk for this occurrence is low in patients with microprolactinoma, there is a general agreement that the drug can be stopped once pregnancy is diagnosed. In patients with macroprolactinoma the risk of tumour enlargement is higher. Therefore, primary therapy with bromocriptine until the tumour has shrank is suggested before pregnancy is attempted. Bromocriptine should be stopped as soon as pregnancy is confirmed …
 
14 Syed Ali Imran, Ehud Ur, and David B. Clarke. “Managing Prolactin-Secreting Adenomas During Pregnancy.” Canadian Family Physician. April 2007 vol. 53 no. 4 653-658. http://www.cfp.ca/content/53/4/653.full 
 
Abstract
OBJECTIVE To determine an appropriate approach to managing prolactin-secreting adenomas of varying severity in pregnant women.
SOURCES OF INFORMATION MEDLINE was searched using the key words “hyperprolactinemia,” “prolactinoma,” “pregnancy,” and “management.” Experience from a multidisciplinary tertiary care centre was also reviewed. Recommendations are based on mostly levels II and III evidence.
MAIN MESSAGE With appropriate management, most women with hyperprolactinemia can achieve pregnancy. Although most women with prolactin-secreting adenomas during pregnancy need only careful observation, others might require medical treatment or even surgical evacuation. Ideally, such patients should be managed by multidisciplinary teams. In the absence of such teams, most pregnant women with small tumours can be managed safely by their primary physicians. Those with large tumours should be referred to specialists.
CONCLUSION Family physicians play an important role in managing women with prolactinomas during pregnancy. Knowledge of current approaches to management is crucial in determining when and how to refer these patients. Prolactin-secreting adenomas are the most commonly encountered pituitary tumours in women of childbearing age.1 Hyperprolactinemia interferes with the hypothalamic-pituitary-ovarian axis at various levels and is responsible for about a third of all cases of female infertility.2 Although the true prevalence of hyperprolactinemia is difficult to establish, it is estimated that among women presenting with reproductive disorders, approximately 15% with anovulation and 43% with anovulation and galactorrhea have hyperpro-lactinemia.3 With adequate management, most women are expected to achieve successful pregnancies; however, managing prolactinomas during pregnancy poses a unique challenge.
When there is no dedicated multidisciplinary team, family physicians have an important role in managing these patients. This article focuses on the issues pertaining to management of prolactinomas during pregnancy. These issues are illustrated by 3 clinical cases of varying severity. The purpose of this article is to help family physicians provide high-quality care to most pregnant women with uncomplicated prolactinomas and identify patients who need to be referred to specialists.
 
15 Christin-Maître S, Delemer B, Touraine P, Young J. “Prolactinoma and estrogens: pregnancy, contraception and hormonal replacement therapy.”  Annales d’Endocrinologie (Paris). 2007 Jun;68(2-3):106-12. Epub 2007 May 30. http://www.ncbi.nlm.nih.gov/pubmed/17540335 
 
Abstract
The stimulatory role of estrogen on prolactin secretion and on proliferation of lactotropic cells is well established in terms of physiology but could this phenomenon be extended to include harmful effects of estrogens on prolactinoma? The aim of this review is to provide an up-to-date assessment of this subject with regard to pregnancy, use of contraceptive pills and postmenopausal hormone replacement therapy. Dopamine agonists allow women presenting prolactinoma to recover their ovulation cycles and become pregnant. There is no adverse data concerning the safety of dopamine agonists such as bromocriptine, if the woman is treated during the first trimester of pregnancy but there is little information regarding the most recent treatments such as cabergoline or quinagolide. In women with microadenomas, pregnancy generally has little impact on their adenoma, delivery is normal and breast-feeding is allowed. Concerning macroprolactinomas, tumor progression during pregnancy is possible and endocrine follow-up remains necessary. Contraceptive pills containing estrogen and progestins are currently the best-tolerated and the most effective contraception. This type of contraceptive has long been avoided in patients presenting prolactinoma. While the literature has little to say on this subject and provides no adverse information, professional experience suggests that this attitude should be amended and that women presenting microprolactinoma should be allowed to use current contraceptive pills (containing 30 microg or less of ethinyl estradiol). The most important problem to overcome with this type of prescription, which masks the clinical consequences of hyperprolactinemia, is the possibility of overlooking hypophyseal disease that could result from this approach. The problem of macroprolactinoma is different; the possibility of prescribing contraceptive pills must be evaluated on a case-by-case basis and the impact of the drug on the adenoma must be very closely monitored. Estrogen replacement therapy in patients presenting hypogonadism should be attempted in patients with a history of prolactinoma and standard-monitoring precautions should be taken. In menopausal women, when replacement therapy is desirable, the presence of a microprolactinoma should not by itself avoid this prescription.
 
32 Colao A. “Pituitary Tumors: The Prolactinoma” Best Practices and Research in Clinical Endocrinology and Metabolism. 2009 Oct;23(5):575-96. Source: Department of Molecular and Clinical Endocrinology and Oncology, Federico II University http://www.ncbi.nlm.nih.gov/pubmed/19945024 
 
Abstract
This review focus on the epidemiology, diagnosis and treatment of prolactinomas. In particular, attention was given to recent data showing a high prevalence of these tumours in the general population, 3-5 times higher than previously reported. The diagnosis of hyperprolactinaemia has been simplified in recent years, and only prolactin (PRL) assay and magnetic resonance imaging of the sella are required. Nonetheless, macroprolactinaemia should be assessed in patients with hyperprolactinaemia in the absence of clinical symptoms of elevated PRL levels. The recent evidence that medical therapy with dopamine agonists should be continued lifelong has been confirmed by several studied. The patients achieving disappearance of the tumours and suppression of PRL levels during treatment are those showing the highest likelihood to have persistent remission of hyperprolactinaemia after treatment withdrawal.
 
34 Mahmoud M Suhail, Weijuan Wu, Amy Cao, Fadee G Mondalek, Kar-Ming Fung, Pin-Tsen Shih, Yu-Ting Fang, Cole Woolley, Gary Young, and Hsueh-Kung Lin. “Boswellia sacra essential oil induces tumor cell-specific apoptosis and suppresses tumor aggressiveness in cultured human breast cancer cells” BioMedCentral Complementary and Alternative Medicine. 2011; 11: 129. Published online 2011 December 15. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258268/ 
 
Abstract
Background
Gum resins obtained from trees of the Burseraceae family (Boswellia sp.) are important ingredients in incense and perfumes. Extracts prepared from Boswellia sp. gum resins have been shown to possess anti-inflammatory and anti-neoplastic effects. Essential oil prepared by distillation of the gum resin traditionally used for aromatic therapy has also been shown to have tumor cell-specific anti-proliferative and pro-apoptotic activities. The objective of this study was to optimize conditions for preparingBoswellea sacra essential oil with the highest biological activity in inducing tumor cell-specific cytotoxicity and suppressing aggressive tumor phenotypes in human breast cancer cells.
Methods
Boswellia sacra essential oil was prepared from Omani Hougari grade resins through hydrodistillation at 78 or 100 oC for 12 hours. Chemical compositions were identified by gas chromatography-mass spectrometry; and total boswellic acids contents were quantified by high-performance liquid chromatography. Boswellia sacra essential oil-mediated cell viability and death were studied in established human breast cancer cell lines (T47D, MCF7, MDA-MB-231) and an immortalized normal human breast cell line (MCF10-2A). Apoptosis was assayed by genomic DNA fragmentation. Anti-invasive and anti-multicellular tumor properties were evaluated by cellular network and spheroid formation models, respectively. Western blot analysis was performed to study Boswellia sacra essential oil-regulated proteins involved in apoptosis, signaling pathways, and cell cycle regulation.
Results
More abundant high molecular weight compounds, including boswellic acids, were present in Boswellia sacra essential oil prepared at 100 oC hydrodistillation. All three human breast cancer cell lines were sensitive to essential oil treatment with reduced cell viability and elevated cell death, whereas the immortalized normal human breast cell line was more resistant to essential oil treatment. Boswellia sacra essential oil hydrodistilled at 100 oC was more potent than the essential oil prepared at 78 oC in inducing cancer cell death, preventing the cellular network formation (MDA-MB-231) cells on Matrigel, causing the breakdown of multicellular tumor spheroids (T47D cells), and regulating molecules involved in apoptosis, signal transduction, and cell cycle progression.
Conclusions
Similar to our previous observations in human bladder cancer cells, Boswellia sacra essential oil induces breast cancer cell-specific cytotoxicity. Suppression of cellular network formation and disruption of spheroid development of breast cancer cells by Boswellia sacra essential oil suggest that the essential oil may be effective for advanced breast cancer. Consistently, the essential oil represses signaling pathways and cell cycle regulators that have been proposed as therapeutic targets for breast cancer. Future pre-clinical and clinical studies are urgently needed to evaluate the safety and efficacy of Boswellia sacra essential oil as a therapeutic agent for treating breast cancer.
 
37 Sliutz G, Speiser P, Schultz AM, Spona J, Zeillinger R. “Agnus castus extracts inhibit prolactin secretion of rat pituitary cells.” Hormone and Metabolic Research (University of Vienna, Austria). 1993 May;25(5):253-5. http://www.ncbi.nlm.nih.gov/pubmed?term=vitex%20agnus%20pituitary%20gland 
 
Abstract
In our studies on prolactin inhibition by plant extracts we focused on the effects of extracts of Vitex agnus castus and its preparations on rat pituitary cells under basal and stimulated conditions in primary cell culture. Both extracts from Vitex agnuscastus as well as synthetic dopamine agonists (Lisuride) significantly inhibit basal as well as TRH-stimulated prolactin secretion of rat pituitary cells in vitro and as a consequence inhibition of prolactin secretion could be blocked by adding a dopamine receptor blocker. Therefore because of its dopaminergic effect Agnus castus could be considered as an efficient alternative phytotherapeutic drug in the treatment of slight hyperprolactinaemia.
 
39 Leblanc H, Yen SS. “The effect of L-dopa and chlorpromazine on prolactin and growth hormone secretion in normal women.” American Journal of Obstetrics and Gynecology. 1976 Sep 15;126(2):162-4. http://www.ncbi.nlm.nih.gov/pubmed/961756
 
Abstract
The time course of simultaneous changes in prolactin (PRL) and growth hormone secretion in response to a single dose of L-dopa and chlorpromazine was determined in normal women. L-Dopa induced greater, but shorter (30 minutes), growth hormone release than concomitant suppression of PRL secretion. The PRL peak following chlorpromazine occurred at the same time as the nadir of PRL after L-dopa (3.5 hours). The quantity of PRL release inhibited by L-dopa equaled the amount of PRL secretion during the period of rebound, suggesting L-dopa inhibits PRL release, but not synthesis, by the pituitary.